Viral Syndrome. The main causes of virilization of the female body

Viril syndrome (virilism)- a symptom complex characterized by the appearance in females of secondary sexual characteristics characteristic of male body. The pathological condition in a certain way affects the appearance of a woman, namely: the structure and proportions of the body become similar to those of men, the muscular system is overdeveloped, the mammary glands undergo atrophy, the clitoris enlarges, resembling a male penis, the voice "groans". Viril syndrome can occur both in childhood and in old age.

The very first sign of the virile syndrome is hirsutism - excessive male pattern hair, i.e. hair growth in the chin area and above the upper lip, which should be differentiated from hypertrichosis, which is characterized by an increase in the growth and number of vellus hair on the body, occurring against the background of normally developed secondary sexual characteristics, and not dependent on androgen secretion.

Viril syndrome is classified depending on its origin into:

1. Constitutionally hereditary viril syndrome when there are no obvious flaws in the structure and work of the endocrine glands (can be observed in women from the southern regions, or in people with increased sensitivity of hair follicles to the influence of male sex hormones);

2. Adrenal Viril Syndrome, which develops as a result of hyperplastic processes in the adrenal cortex, or with the development of a tumor process in them;

3. Ovarian viril syndrome, which is caused by the development in the ovaries of neoplasms such as luteoma, lipoid cell tumors, as well as sclerocystic processes in them;

4. pituitary virile syndrome due to the occurrence of Itsenko-Cushing's disease, acromegaly.

In the clinic, it is customary to distinguish two forms of the viril syndrome, which differ from each other in origin:

Viril syndrome of adrenal origin and

Viril syndrome of ovarian origin.

Causes and mechanisms of development of the viril syndrome of adrenal origin

Viril syndrome of adrenal origin, characterized by excessive function of the adrenal cortex due to a hyperplastic or neoplastic process, otherwise called adrenogenital syndrome. Primary adrenal tumors are extremely rare. More often, corticosteromas, androsteromas and androcorticosteromas lead to the development of the viril syndrome.

The basis of the mechanism for the development of adrenogenital syndrome is a defect in the enzyme system of the adrenal cortex, namely, the cortex loses the ability to form hydrocortisone and cortisone from 17a-hydroxyprogesterone. To compensate for the insufficient production of hydrocortisone in the adrenal cortex, the adenohypophysis increases the production of adrenocorticotropic hormone, which leads to hyperplasia of the adrenal cortex and an even greater increase in the production of 17a-hydroxyprogesterone. An excess amount of this metabolite stimulates the formation of pregnantriol, androsterone and other androgens, increasing their secretion. The accumulation of a high concentration of male sex hormones in the female body entails its masculinization, and also inhibits the gonadotropic function of the pituitary gland, resulting in a decrease in the function of the female gonads.

Signs of the viril syndrome of adrenal origin

Depending on the age of the patients, there are characteristics adrenogenital syndrome. So, for example, congenital adrenogenital syndrome is characterized by a violation of the development of the external genital organs with the normal development of the internal genital organs, according to the type of pseudohermaphroditism. Moreover, the earlier the effect of an excess of male sex hormones is manifested, the more pronounced it is.

Congenital adrenogenital syndrome occurs in one case in 5000 births, and in 30% of cases, an anomaly in the development of the external genital organs is combined with a salt-wasting syndrome, which is characterized by nausea, vomiting, dehydration and collapse. Newborns with this combination of pathologies die, as a rule, in the first weeks after birth due to a decrease in the production of mineralocorticoid hormones. With congenital adrenal hyperplasia after the birth of a girl, there is an aggravation of virilization.

Viril syndrome of adrenal origin, which develops after birth or in adolescence, is characterized, along with viril features, by precocious puberty. The development of the syndrome is more often associated with the presence of a neoplasm in the adrenal glands. A large amount of male sex hormones secreted by the tumor leads to acne, coarsening of the voice, atrophy of the uterus and ovaries. The body of the child takes on a disproportionate appearance due to the elongated upper body and short thick legs. The reason for this is enhanced growth bones, leading to early closure of the growth zones, as a result of which children stop developing early and remain stunted. Their external genital organs are without pathological changes.

In the early period of puberty, the viril syndrome of adrenal genesis can develop in two ways:

- "fat type", or obesity according to the type of Itsenko-Cushing's disease, which develops with adrenal corticosteroma;

- "muscle type", characterized by excessive development muscular system characteristic of androsteroma of the adrenal glands.

Adrogenital syndrome, which developed in the body of a mature woman, is characterized by virilization of varying severity and can be caused by both hyperplastic and tumor processes in the adrenal glands. When examining women, excessive male-type hair growth, menstrual irregularities (oligomenorrhea, amenorrhea), infertility, reduction of mammary glands, atrophy of the uterus and ovaries, increased pigmentation of the external genital organs, coarsening of the skin are revealed. Against the background of overdeveloped muscles, there is a significant decrease in the subcutaneous fat layer. Acne appears on the face and body, the clitoris increases, and sexual desire decreases. Hirsutism is considered constant, often the only and one of the first signs of the virile syndrome.

Viril syndrome, which develops against the background of corticosteroma, is manifested, as a rule, by hirsutism, increased blood pressure, osteoporosis, "cushingoid" obesity, the appearance of striae and acne, and the development of steroid diabetes. Virilism associated with the development of androsteroma is usually more pronounced, along with virilization, patients have headaches, general weakness, lowering blood pressure and other signs indicating a weakening of the glucocorticoid and an increase in the androgenic function of the adrenal cortex.

Causes and mechanisms of development of the viril syndrome of ovarian genesis

Virilism can occur with sclerocystic lesions of the ovaries, or with masculinizing tumors of the ovaries. The mechanism of development of sclerocystic ovaries or Stein-Leventhal syndrome is not fully understood. There are a number of theories of the origin of the syndrome - the theory of pituitary origin, the theory of adrenal origin, the theory of morphofunctional disorders in the ovaries, each of which is confirmed.

The origin of ovarian neoplasms of the masculinizing type, which secrete a large amount of testosterone, as a result of which signs of masculinization develop, is also not known for certain. Most authors believe that they grow from the remnants of the male part of the gonad in the ovaries. The basis of the mechanism for the development of hormonally active ovarian tumors is a violation of the production of follicle-stimulating, luteotropic and adrenocorticotropic hormones in the pituitary gland. Since the formation of female sex hormones from progesterone is associated with androgens, with defects in enzymatic processes, there is a violation of the conversion of androsterone into estrogens, and as a result, an excess of male sex hormones is formed in the ovaries.

Viril syndrome of ovarian genesis - symptoms

Stein-Leventhal syndrome, or sclerocystic ovarian syndrome, leading to the development of virilism, is most often diagnosed at 20-30 years of age. Hirsutism is the earliest symptom that occurs in about half of patients. varying degrees severity - from slight facial hair to total throughout the body. Hirsutism is combined with atrophy of the mammary glands, uterus, clitoral hypertrophy, a decrease in the timbre of the voice, impaired menstrual function. In the vast majority of cases, women with a similar diagnosis are infertile, 20-40% of them are obese.

Clinical signs in arrhenoblastoma, which is the most commonly diagnosed masculinizing ovarian neoplasm in women aged 20-35 years, are similar to those described above and consist mainly of menstrual disorders in the form of oligomenorrhea, which subsequently turns into amenorrhea, atrophy of the mammary glands and uterus, hirsutism, decreased libido, clitoral hypertrophy. During a gynecological examination, an ovarian tumor is determined, with an increase in the size of which the patient complains of pain in the lower abdomen. Arrhenoblastoma undergoes malignancy in a quarter of cases, which leads to the progression of the viril syndrome.

Lipoid cell tumors, which are a type of masculinizing ovarian tumors, are often found during menopause. Symptoms of tumors are similar to those of arrhenoblastoma, but may be more diverse due to the ability of the tumor to produce not only androgens, but also corticosteroids, as well as progesterone. Their size is small, which makes them difficult to palpate, and they do not cause pain, so their early diagnosis is difficult. Malignancy of these tumors is observed in one case out of five identified. This type of ovarian neoplasm, in addition to the symptoms of virilization, also causes a persistent increase in blood pressure, carbohydrate metabolism disorders, and the development of obesity.

Viril Syndrome Diagnosis

The diagnostic algorithm of the virile syndrome should be based on anamnesis data, laboratory and instrumental research methods, and also be based on the conclusion of an endocrinologist, gynecologist and oncologist.

A blood test to detect the level of androgens allows you to determine the source and nature of hyperandrogenemia. Viril syndrome of ovarian genesis is characterized by an increase in the level of testosterone and androstenedione, and for viril syndrome of adrenal genesis - an increase in the concentration of epiandrosterone in the blood.

Identification of the localization of the cause that causes the development of the virile syndrome is carried out using ultrasound examination of the ovaries and adrenal glands, radiography of the adrenal glands, computed and magnetic resonance imaging, and pneumopelvigraphy. Laparoscopy of the ovaries allows you to evaluate the tumor material at histological examination.

Treatment of the viril syndrome

The goal of treating the viril syndrome is to eliminate the cause that led to an increase in the concentration of androgens in the blood. Therefore, with the tumor genesis of the viril syndrome, they resort to operational methods treatment - removal of neoplasms of the adrenal glands or ovaries, and in functional forms of hyperandrogenemia, along with surgical and conservative methods, hormone therapy with synthetic estrogen preparations, antiandrogens (veroshpiron, Diana) is used. If conservative therapy is ineffective, they resort to wedge resection of the ovaries or their diathermocoagulation.

The prognosis for the functional type of the virile syndrome is favorable, since as a result of treatment, patients recover menstrual cycle and reproductive function. Viril syndrome of tumor origin ends successfully in case of detection and removal of the tumor that caused its development.

• Infertility

  In medicine, infertility refers to the inability of a person to bear children, while the term "infertility" is used both in relation to a woman and in relation to a man.

• hirsutism

  hirsutism - overgrowth coarse pigmented hair in women on the face and body according to the male pattern. The appearance of coarse rod hair in certain areas - above the upper lip, chin (like a mustache and beard), on the back, abdomen, hips and other androgen-dependent areas that are highly sensitive to male sex hormones, causes cosmetic problems, accompanied by development in women psychological complexes

• polycystic ovary syndrome

  Polycystic ovary syndrome is an endocrine pathology of the female body, which is characterized by a violation of the menstrual cycle with the absence of the ovulatory process and, as a result, an increased level of male sex hormones - androgens

• Androsteroma

  Androsteroma - a tumor originating from the reticular zone of the adrenal cortex and characterized by excessive production of androgens

• Corticosteroma

  Corticosteroma is a hormonally active neoplasm of the adrenal cortex, which is manifested by symptoms of hypercortisolism (Itsenko-Cushing's syndrome)

• Endocrinologist's consultation

  Specialists of the North-Western Center of Endocrinology diagnose and treat diseases of the endocrine system. The endocrinologists of the center in their work are based on the recommendations of the European Association of Endocrinologists and the American Association of Clinical Endocrinologists. Modern diagnostic and therapeutic technologies provide optimal treatment results.

• Consultation of a gynecologist-endocrinologist

  A gynecologist-endocrinologist is one of the most sought-after specialists at the North-West Endocrinology Center. Consultations of a gynecologist in St. Petersburg are among the most popular, and consultations of a gynecologist-endocrinologist are especially popular. The vast majority of diseases that bring women to a consultation with a gynecologist have the causes of their problems in the disrupted functioning of the endocrine system. That is why many patients who seek help at the endocrinology center need a consultation with a gynecologist-endocrinologist, and in some cases, also with a consultation with an endocrinologist.

These groups are fundamentally different in etiology, pathogenesis and methods of correction.

virilization(from the Latin virilis - male, characteristic of a man) - an active process associated with the activity of androgens and characterized by the appearance and development of male sexual phenotypic traits: the formation of the penis, urethra, scrotum (and the descent of the testicles into it), the development of hair growth in androgen-dependent zones, the appearance of male pattern baldness, changes in the cartilage of the larynx and the change (coarseness) of the voice, male proportions of the skeleton and the development of muscle tissue. Virilization in men is a normal consequence of the joint harmonious functioning of the adrenal cortex and testicles. For women, virilization is normally possible at puberty (due to the activation of the function of the adrenal glands) in the form of adrenarche: the appearance of pubic and axillary hair growth. The progression of androgen-dependent signs in a woman beyond the adrenarche is considered a pathology and requires appropriate treatment.

Insufficient virilization of men- a complex of symptoms that is formed under the influence of insufficient production or insufficient action of androgens on tissues. For women, insufficient virilization actually has no clinical significance, because it is manifested only by the absence of hair growth in androgen-dependent zones.

Feminization(from the Latin femina - woman) - an active process associated with the activity of female sex hormones - estrogens and characterized by the appearance and development of phenotypic characteristics characteristic of the female sex. Feminization is an integral part of female sexual development (as virilization is of male sexual development) and is completely uncharacteristic of the opposite sex. For men, feminization is always a symptom of a serious illness caused by the appearance in the body of increased activity or an absolute amount of the aromatase enzyme, and, accordingly, estrogens. At puberty in boys, these may be tumors of the gonads containing aromatase and producing estrogens. Thus, Sertoli cell tumors lead to an absolute excess of female sex hormones, which leads to feminization - the development of gynecomastia. In men, the source of aromatization is also adipose tissue, liver, liver tumors. In all cases, excess estrogen, in addition to feminization, leads to suppression of the hypothlamus-pituitary-gonadal system, which leads to a delay in puberty and then to the formation of infertility. The difference between the feminization syndrome and the syndrome of insufficient virilization in men is the need in the first case to start a diagnostic search for the site of androgen aromatization (tumor) and its surgical removal. In the second case, androgen deficiency and virilization must be corrected by prescribing androgens.

Protocol for examining adolescents with gynecomastia

1. the use of medicines;
2. drug use;
3. excessive consumption of beer;
4. hereditary burden.

Objective examination:

1. measurement of height and weight, waist circumference and calculation of BMI;
2. palpation of the mammary glands;
3. palpation of regional lymph nodes;
4. examination of hair growth of androgen-dependent zones;
5. assessment of the proportions of the skeleton;
6. examination of the scrotum;

Instrumental diagnostics:

1. Ultrasound of the mammary glands;
2. Ultrasound testicles;
3. TIAB of the glandular tissue of the breast only in cases of suspected malignancy;
4. TIAB testicular tumors in cases of its detection;
5. mammography in cases of suspected breast carcinoma;
6. Ultrasound of the liver and kidneys or other organs (or MRI) for suspected ectopic extragonadal production of hCG.

Laboratory diagnostics:

1. clinical blood test;
2. biochemical blood test (ALAT, AST, bilirubin, creatinine, urea, alkaline phosphatase, sodium, potassium);
3. hormonal examination.

Laboratory cytogenetic and molecular genetic diagnostics:

1. karyotype (only in cases of hypergonadotropic hypogonadism);
2. androgen receptor mutations (with the exclusion of all forms of hypogonadism and feminization syndromes);
3. mutations of other genes depending on the alleged pathology, taking into account the algorithm for the differential diagnosis of gynecomastia.

Classification of diseases accompanied by the development of gynecomastia

Syndromes of insufficient virilization

• Hypogonadism.
• Hypogonadotropic hypogonadism:
• insufficiency of the function of the hypothalamus and pituitary gland with anosmia (Kallmann syndrome);
• sporadic forms;
• chromosomal forms;
• autosomal dominant forms;
• FGFR1 mutations (Kallmann 2 syndrome);
• PROKR2 mutations (Kallmann 3 syndrome);
• X-linked forms;
• KAL-1 mutations (Kallmann 1 syndrome);
• syndromic forms;
• CHARGE syndrome;
• Berjeson-Forssmann-Lehmann syndrome.
• Insufficiency of the function of the hypothalamus and pituitary gland without anosmia:
• chromosomal forms;
• Prader-Willi syndrome;
• autosomal dominant forms;
• FGFR1 mutations;
• PROKR2 mutations;
• PROP1 panhypopituitarism;
• HESH1 panhypopituitarism;
• LHX3 panhypopituitarism;
• prohormone convertase 1 mutation;
• autosomal recessive forms;
• Bardet-Biedl syndrome;
• GPR54 gene mutation;
• Laurens-Moon syndrome;
• damage to the adenohypophysis in hemochromatosis (HFE congenital hemochromatosis, juvenile congenital hemochromatosis, TFR2 congenital hemochromatosis);
• X-linked forms (hypoplasia of the adrenal cortex congenital X-linked)
• Hypogonadotropic hypogonadism in violation of the structure of hormone molecules:
• LH β-subunit mutations;
• leptin molecule mutation.
• Hypogonadotropic hypogonadism with insufficient sensitivity of receptors to hormones:
• gonadoliberin receptor inactivating mutations;
• leptin receptor gene mutation.
• Hypogonadotropic hypogonadism acquired forms:
• surgery on the hypothalamic-pituitary region.
• Tumors and malformations of the hypothalamic-pituitary region:
• hamartoma (Pallister-Holl syndrome, neurofibromatosis type 1);
• astrocytoma;
• craniopharyngioma;
• pituitary adenoma;
• glioma.
• Hypergonadotropic hypogonadism.
• Primary Leydig cell failure and gonadal dysgenesis:
• X polysomy syndrome (Klinefelter's syndrome);
• 46, XX testiculogenic disorders of sexual development (mutations of the SRY gene, de la Chapelle syndrome - de la Chappel);
• 46,XY disorders of sexual development and 46,XY complete gonadal dysgenesis;
• mutations in the DHH gene;
• mutations in the NR0B1 gene;
• mutations in the NR5A1 gene;
• mutations in the WNT4 gene;
  mutations of the 5LG gene;
• autoimmune orchitis.
• Acquired forms of hypergonadotropic hypogonadism:
• orchidectomy.
• Syndromes of insufficiency of the activity of steroidogenesis enzymes:
• organic forms:
• 5α-reductase deficiency syndrome;
• 17β-hydroxysteroid dehydrogenase deficiency;
• SF-1 deficiency syndrome;
• dosage forms:
• 5α-reductase inhibitors;
• steroidogenesis blockers are non-selective.
• Syndromes of insufficient sensitivity of receptors to hormones:
• organic forms:
• androgen insensitivity syndrome;
• testicular feminization;
• incomplete form of the syndrome;
• minimal forms of androgen resistance;
• Kennedy's illness;
• dosage forms:
• androgen receptor blockers;
• gonadoliberin receptor agonists;
• gonadoliberin receptor antagonists.

Feminization Syndromes:

• Hormonally active tumors:
• estrogen-producing tumors;
• testicular tumors of the sex cord (including Peutz-Jeghers syndrome, Carney complex, McCune-Albright syndrome);
• liver tumors with aromatase activity;
• HCG-producing tumors;
• testicular tumors of the sex cord;
• extragonadal localization of the tumor;
• prolactinoma.
• Syndromes of excessive activity of aromatase of non-tumor origin:
• aromatase overactivity syndrome;
• obesity;
• liver disease, liver failure;
• drugs that enhance aromatase activity.
• Dosage forms:
• estrogens, phytoestrogens;
• androgens and anabolic steroids;
• drugs that increase prolactin levels;
• drugs that affect the metabolism of androgens and estrogens.
• Diseases accompanied by the development of gynecomastia.
• Syndromes of insufficient virilization, hypogonadism.

Hypogonadism is hypergonadotropic. Klinefelter syndrome. In the name of this pathology, the nomenclature is most often used: Klinefelter's syndrome, or classic (trisomic) Klinefelter's syndrome, less often - XXY-chromosome syndrome. The prevalence of the disease: 1 case per 500 newborn boys. Diagnostic criteria are not well defined, but two criteria are more commonly used: hypergonadotropic hypogonadism and a 47,XXY karyotype. Clinical characteristics in men with Klinefelter syndrome are determined primarily by the number of cells carrying an extra X chromosome, and secondarily by blood testosterone levels and androgen receptor sensitivity. Most men are characterized by phenotypic polymorphism. Tall stature and eunuchoid physique are noted. However, this does not always occur. Quite rarely, violations of the intellect, lability of character are described. The most characteristic anomalies of the reproductive system: hypergonadotropic hypogonadism, puberty disorders, azoospermia or severe oligozoospermia (very rarely, with mosaic forms).

46, XX testicular disorders of sexual development meet with a frequency of 1:20,000 newborn boys. Previously, the terms "46, XX-male syndrome" and "de la Chapell syndrome" were used, but they have now been abandoned. In men, symptoms of insufficient virilization are noted: hypospadias, cryptorchidism, gynecomastia. Anomalies of the reproductive system include azoospermia, cryptorchidism (15%, more often in SRY-negative variant), penoscrotal hypospadias with or without notochord (20%, more often in SRY-negative variant). 20% of newborns have ambivalent genitalia (more often with SRY-negative variant). Hypergonadotropic hypogonadism is often formed. Testicular biopsy reveals reduced vas deferens, peritubular fibrosis, complete Sertoli cell syndrome, and Leydig cell hyperplasia.

Leydig cell aplasia. The most commonly used synonyms for the syndrome are: LH receptor inactivating gene mutation, Leydig cell hypoplasia syndrome. Diagnostic criteria for the syndrome. Insufficient prenatal and postnatal virilization, as a rule, these disorders are due either to the absence of mesenchymal precursors of Leydig cells, or to insufficient receptor sensitivity of Leydig cells to human chorionic gonadotropin / luteinizing hormone. This condition is accompanied by testosterone deficiency and the development of hypergonadotropic hypogonadism. Extra-genital developmental anomalies are not typical for this syndrome. The diagnosis of the "complete (expanded)" form of the syndrome is established when severe anomalies in the structure of the external genital organs are detected. In most cases, cryptorchidism is found. The vas deferens is partially formed, derivatives of Mullerian structures are absent, since the production of anti-Mullerian hormone by Sertoli cells is not disturbed. For the patient, the female gender is selected, and then such patients are brought up as girls. An incomplete form of the syndrome is established if phenotypic manifestations of hypergonadotropic hypogonadism, micropenis, hypospadias and infertility are detected.

Idiopathic hypogonadotropic hypogonadism- this is a group of diseases combined into one group as a result of the presence of a common pathological link: a violation of the production of gonadotrophs (LH and FSH) in the adenohypophysis. The frequency of occurrence of IHH, filed various authors, ranges from 1:10000 to 1:86000. The male/female ratio is 4:1. There are two types of idiopathic hypogonadotropic hypogonadism: IHH with anosmia, or Kallmann syndrome (60% of IHH cases), and IHH without anosmia (40% of IHH cases). Regardless of the variant, IHH has a clinical picture common to all patients. Newborn boys often present with micropenis (penis length less than 1 cm at birth) and cryptorchidism. In puberty there is a delay in sexual development. Testicular volume is less than 4 ml. In most cases, puberty is absent. However, in rare cases partial puberty or late formation of puberty at 19-21 years is possible. Low levels of testosterone and estradiol lead to the formation of eunuchoid proportions of the skeleton. Adrenarche usually proceeds without disturbance. In adult men, azoospermia or aspermia is detected. Cases of detection in men with IHG of oligozoospermia are rarely described. Histological examination of the biopsy of the testicles reveals hypospermatogenesis or Sertolicellular syndrome. The second option is the most unfavorable for the restoration of fertility.

Differential Diagnosis

In newborn boys, other causes of cryptorchidism and microgenitalism must be excluded: androgen insensitivity syndrome, primary hypogonadism, and gonadal dysgenesis. Hormonal tests with gonadoliberin and chorionic gonadotropin have low sensitivity and specificity. In some cases, the spontaneous formation of puberty is described. In adults, the diagnosis of IHH is established only after exclusion of other causes that led to the defeat of the pituitary gland: pituitary adenoma, pituitary apoplexy, hypopituitarism due to irradiation of the pituitary gland or brain, surgical removal of the pituitary gland. Search needed systemic diseases: hemochromatosis, sarcoidosis, histiocytosis. Exclusion of iatrogenic pharmacological causes: taking a-GnRH, ant-GnRH, glucocorticoids. The cause of the development of idiopathic hypogonadotropic hypogonadism with anosmia (Kallmann syndrome, or de Mersier olfactogenital dysplasia) is a whole spectrum of gene mutations, however, in 70-80% of cases, molecular genetic studies do not reveal changes in genes (the so-called sporadic forms).

Diseases associated with the development of gynecomastia

Syndromes of insufficient enzymatic activity of steroidogenesis of sex hormones

17β-hydroxysteroid dehydrogenase type 3 deficiency. There are no exact data on the incidence of 17β-hydroxysteroid dehydrogenase type 3 deficiency (17β-hydroxysteroid dehydrogenase type 3 deficiency), however, this is the most common disease accompanied by impaired steroidogenesis in men. The cause of the disease is an isolated violation of the last stage of steroidogenesis. Often these patients are brought up as girls, however, excessive virilization develops at puberty due to the intact peripheral conversion of androstenedione to testosterone. In adult men during puberty, as LH production increases, blood testosterone levels may rise to lower levels of normal values. In the case of complete forms of enzyme deficiency, hypergonadotropic hypogonadism develops.

3β-hydroxysteroid dehydrogenase type 2 deficiency. In the available literature, 3β-hydroxysteroid dehydrogenase type 2 deficiency syndrome is synonymous with the term "HSD2 gene mutation", which fully reflects the etiology of deficiency of this enzyme of adrenal and gonadal steroidogenesis. The disease is very rare, and accurate data. Deficiency of precursors of steroidogenesis leads to impaired androgen production by the testicles and the development of hypergonadotropic hypogonadism. The disease is accompanied by insufficiency of glucocorticoids and mineralocorticoids. A salt-wasting syndrome develops: hyponatremia, hypokalemia, hypovolemia, acidosis.

Syndrome of 17α-hydroxylase and 17,20-lyase combined deficiency. A synonym for the syndrome of 17α-hydroxylase and 17,20-lyase combined deficiency is the CYP17 mutation gene. The syndrome is rare.

5α-reductase deficiency. The clinical picture of the disease is due to a violation of the peripheral conversion of testosterone to dihydroteststerone. The disease develops only in men. Boys at birth have an abnormal structure of the genitals of varying degrees of virilization. In most cases, the development of urogenital sinus or hypospadias of varying severity is observed.

Diseases accompanied by the development of gynecomastia: syndromes of insufficient sensitivity of receptors

Androgen resistance syndrome. The incidence of complete androgen resistance varies from 2:100,000 to 5:100,000 newborns. The prevalence of incomplete and minimal forms of the disease is unknown. Clinical features suggestive of the syndrome include the absence of extragenital malformations, two non-dysplastic testicles, absent or vestigial derivatives of the Müllerian ducts (fallopian tubes, uterus, cervix), and the presence of a shortened vagina. The full form of the syndrome is called "testicular feminization", which is not true enough. The clinical characteristic of the full form of the disease consists of a female phenotype, an isolated delay in menarche, and primary amenorrhea. The incomplete form of the disease is called Reifenstein's syndrome. Usually formed scrotal-perineal hypospadias or urogenital sinus. Gynecomastia is always present. Cryptorchidism or testicles in a hypoplastic split scrotum are determined. The 3rd variant is characterized by the following features: the penis is formed with capitate or stem hypospadias. Less commonly, perineal hypospadias is seen with a normal-sized penis and testicles in the scrotum. As a variant of the syndrome: severe hypospadias is formed with a micropenis, a split scrotum and cryptorchidism. Gynecomastia in all patients develops at puberty. Minimum Forms androgen resistance syndromes are characterized by the formation of a male phenotype in a patient with a normal structure of the external genitalia. However, in puberty, there is insufficient virilization in the form of gynecomastia, and later azoospermia or severe oligozoospermia develops.

Kennedy disease. The prevalence of the disease is 1:50,000 men. The clinical picture of the disease consists mainly of symptoms of acquired insufficient virilization. Patients develop gynecomastia, decrease in testicle volume, form azoospermia or oligozoospermia. These manifestations can develop immediately after puberty or at a later age. A distinctive feature of the disease is the defeat of the spinal lower motor neurons, which is accompanied by weakness of the proximal groups of the mouse and muscle cramps. Also, patients have damage to the bulbar lower motor neurons with the involvement of the nerve bundles of the tongue, lips, perioral region, which is accompanied by dysarthria, swallowing difficulties. These men have no signs of damage to the upper motor neurons (hyperreflexia, spasticity). Neurological symptoms develop only at the age of 20-50 years (sometimes even older). In most cases, there is a family hereditary history of the disease. Form of inheritance of the syndrome: linked to the X chromosome. The disease affects only men, while the carriage in women is asymptomatic. The androgen receptor gene (Xqll-ql2) is involved in the pathogenesis of the syndrome. All patients have an increased number of tandem CAG repeats. Normally, a healthy male has 34 or less CAG triplet. In patients with their number in the region of 36-37, incomplete allele penetrance is observed. More than 38 CAG repeats are accompanied by complete penetrance with a detailed clinical picture.

Diseases accompanied by the development of gynecomastia: feminization syndromes, tumors with excessive aromatase activity

Estrogen-producing gonadal tumors. One of the common causes of gynecomastia in newborns and adolescents is feminization syndromes caused by hyperproduction of estrogens by testicular tumors. Usually, these are sex cord tumors that form from Leydig or Sertoli cells and have increased aromatase activity. In some cases, gynecomastia may develop in patients with hCG-producing testicular tumor or prolactin-secreting pituitary adenoma. Most of these hormone-producing adenomas are sporadic, but hereditary forms that are part of genetic syndromes can also be observed.

Multiple endocrine neoplasia syndrome, type 1. The prevalence of the disease is 1:30,000 people. The diagnosis of MEN1 should be assumed in a patient with 2 of the 3 endocrine tumors listed below: parathyroid tumors (characterized by the formation of hypercalcemia and primary hyperparathyroidism), tumors of the adenohypophysis (prolactin-secreting adenomas, GH-prolactin-secreting adenomas, GH-secreting adenomas, ACTH-secreting adenomas , TSH-secreting adenomas, LH- or FSH-secreting adenomas). In these patients, tumors of the gastroenteropancreatic (GEP) tract are often detected: gastrinomas (Zollinger-Ellison syndrome), insulinomas, glucagonomas, VIP-omas. Tumors of the adrenal glands in this syndrome are described: hormonally inactive, cortisol-secreting, aldosterone-secreting adenomas or pheochromocytoma. Damage to the reproductive system is more often associated with hyperprolactinemia. Gynecomastia is formed, libido decreases, oligozoospermia, asthenozoospermia develop.

Peutz-Jeghers Syndrome. Data on the prevalence of the disease vary among different authors from 1 case per 25,000 to 1 case per 280,000 people. Patients are characterized by the formation of hamartomas. However, additional criteria are required for the diagnosis: hereditary burden to the given syndrome, hyperpigmentation of the mucous membranes, skin, and polyposis of the small intestine. Patients are characterized by gastrointestinal polyposis. Hamartomatous polyps usually develop in the small intestine (96%), colon (27%), rectum (24%), oral cavity (24%). Often accompanied by bleeding and anemia. Sertoli-cell estrogen-producing testicular tumors are often formed in men, which are clinically manifested by gynecomastia.

Karni Complex. Other names of the syndrome are often used in the literature: NAME syndrome (Nevi, Atrial Myxomas, Ephelides), LAMB syndrome (Lentigines, Atrial Myxoma, Blue nevi) or Carney's triad. There are no accurate data on the prevalence of the disease. Different authors describe about 400-600 cases known to them. The diagnosis is established if the patient has the following symptoms: skin manifestations (lentigenosis, blue nevi), myxomas (skin myxomas, myxomas of the heart). Tumors of the endocrine glands are characterized by the formation of primary pigmentary nodular disease of the adrenal glands (ACTH-independent hypercorticism due to multiple adrenocortical nodules). Large-cell calcifying Sertoli cell tumors often develop. Sometimes signs of calcification are found on ultrasound examination of the testicles. The manifestation of the disease is observed more often at the age of 11-27 years. The cause of the pathology: mutations in the PRKAR1A gene. Testicular tumors are detected in 30% of cases in the first decade of life. However, cases of tumor development at the age of 60 years have been described. The clinical manifestation of these adenomas is pubertal gynecomastia. Then the man develops infertility.

Excess aromatase (congenital) syndrome (aromatase excess syndrome). A rare hereditary disease, accompanied by the formation of gynecomastia. In the future, oligozoospermia and asthenozoospermia are formed.

congenital hypothyroidism

Congenital hypothyroidism is one of the most common congenital diseases. thyroid gland in children. The incidence ranges from 1 case per 4000-5000 newborns in Europe and North America up to 1 in 6000-7000 newborns in Japan. In girls, congenital hypothyroidism is recorded 2-2.5 times more often than in boys.

The basis of the disease is a complete or partial insufficiency of thyroid hormones, leading to a delay in the development of all organs and systems. First of all, in the fetus and newborn, the central nervous system suffers from a lack of thyroid hormones. There is a strong correlation between the timing of the start replacement therapy and the index of intellectual development of the child in the future. Favorable mental development can be expected only at the beginning of treatment in the first month of a child's life. In recent decades, there has been a real possibility of mass examination of all newborns for the presence of congenital diseases, such as phenylketonuria, galactosemia, congenital adrenal cortex dysfunction, maple syrup disease, homocystinuria, and congenital hypothyroidism. Screening for phenylketonuria was first carried out in 1961, and 12 years later, in Canada (Quebec), newborns were screened for congenital hypothyroidism by determining their T 4 content by radioimmunoassay on filter paper. Currently, neonatal screening for congenital hypothyroidism is routine and effective method screenings for newborns early diagnosis diseases.

Screening for congenital hypothyroidism makes it possible to diagnose the disease in the first month of a child's life. Availability highly efficient drug for replacement therapy (levothyroxine sodium) allows it to be carried out in the most physiological mode and optimal dosage. Congenital Hy-

thyroidism is a disease in which timely treatment prevents the development mental retardation The child has.

Etiology and pathogenesis

In recent years, in connection with the development of methods of molecular genetic analysis, views on the etiology of congenital hypothyroidism have largely changed. Congenital hypothyroidism is quite heterogeneous in etiology, due to the morphological and functional immaturity of the hypothalamic-pituitary system, the thyroid gland or their anatomical damage during the intrauterine period.

In the vast majority of cases (85-90%), primary congenital hypothyroidism is diagnosed. Among them, approximately 85% are sporadic and 15% are hereditary (Table 18-1). Most sporadic cases are due to thyroid dysgenesis, and cases of ectopic thyroid are observed much more often than its complete absence (agenesis) or hypoplasia. According to various authors, thyroid agenesis is recorded in 22-42%, ectopia in 35-42%, and hypoplasia in 24-36%.

Table 18-1.Etiology and prevalence of the main forms of congenital hypothyroidism

The hypothalamic-pituitary-thyroid system of the fetus develops independently of the influence of the organism of the pregnant woman. By the 10-12th week of intrauterine development, the fetal thyroid gland is able to accumulate iodine and synthesize iodothyronines. By this time, the fetal pituitary may secrete some TSH.

The content of T 4 in the blood serum of the fetus progressively increases from the middle of pregnancy to the time of delivery. The concentration of T 3 in the fetus is relatively low until the 20th week of pregnancy, and then increases significantly, reaching 60 ng / dl by the end of pregnancy. The content of TSH in the fetus gradually increases with increasing gestational age and by the time of delivery is about 10 mIU / l.

T 4 pregnant partially crosses the placenta and affects the development of the fetus (especially its brain). Mostly this influence is carried out in the first weeks of pregnancy until the moment when the synthesis of one's own thyroid hormones begins.

In a fetus that develops in the body of a pregnant woman with hypothyroidism, the risk of developing CNS pathology is increased. On the other hand, with insufficient production of thyroid hormones in the fetus, T4 penetrating the placenta of a pregnant woman can to a certain extent prevent the development of hypothyroidism in him.

At birth and in the first minutes of life, a newborn has a significant release of TSH, the concentration of which by the 30th minute after birth reaches 70 mU/l (in full-term newborns). Then the concentration of TSH gradually decreases, reaching 10 mU/l by the end of the 2-3rd day. A sharp increase in the content of TSH entails a significant increase in the concentrations of T 4 and T 3 during the first hours of a child's life. T 3 is largely formed at the periphery due to conversion processes.

Clinical picture

A typical clinical picture of congenital hypothyroidism in newborns, when it is extremely important to make a diagnosis, is observed in only 10-15% of cases. The most typical signs of the disease in the early postnatal period include:

Post-term pregnancy (more than 40 weeks);

Excess body weight at birth (more than 3500 g);

Puffy face, lips, eyelids, half-open mouth with a wide, "flattened" tongue;

Localized edema in the form of dense "pads" in the supraclavicular fossae, on the back surfaces of the hands, feet;

Signs of immaturity in full-term pregnancy;

Late passage of meconium;

Late discharge of the umbilical cord;

Poor epithelialization of the umbilical wound;

Protracted jaundice.

In the future, at the 3-4th month of life, if treatment has not been started, other clinical symptoms of the disease occur:

Decreased appetite;

Difficulty swallowing;

Lagging behind in weight gain;

Flatulence;

constipation;

Dryness, pallor, peeling of the skin;

Hypothermia (cold hands, feet);

Brittle, dry, dull hair;

Muscular hypotension.

In the later stages, after the 5-6th month of life, the growing delay in the psychomotor and physical development of the child comes to the fore. The proportions of the body in children with hypothyroidism approach chondrodystrophic, the development of the facial skeleton lags behind (wide sunken bridge of the nose, hypertelorism, late closure of the fontanelles). The eruption of teeth is delayed, and then their change. Attention is drawn to cardiomegaly, deafness of heart tones, decrease in blood pressure, decrease in pulse pressure, bradycardia (in children of the first months, the pulse rate may be normal). Children with congenital hypothyroidism have a low, rough voice, cyanosis of the nasolabial triangle, and stridor breathing are often observed. In the absence of adequate treatment of congenital hypothyroidism, cretinism eventually develops.

As additional methods examinations use radiography of the hands (they note a delay in the appearance of ossification nuclei, their asymmetry, a violation of the sequence of their occurrence, epiphyseal dysgenesis serves as a pathognomonic sign), a complete blood count (anemia), a biochemical blood test (hypercholesterolemia), an ECG (a decrease in voltage, a slowdown in conduction, lengthening of systole sinus bradycardia).

To confirm the diagnosis of congenital hypothyroidism, it is necessary to examine the content of thyroid hormones (T3, T4) and TSH in the blood serum. In primary hypothyroidism, the concentrations of T 4 and T 3 are reduced, and the content of TSH significantly exceeds the norm. In secondary hypothyroidism, thyroid hormone concentrations are reduced, and TSH levels may be reduced or normal.

Prior to the widespread introduction of screening for congenital hypothyroidism and radioimmunological methods for determining hormones in blood serum into clinical practice, the diagnosis was established on the basis of clinical and anamnestic data, which led to a late start of replacement therapy.

Summarizing the above clinical signs of congenital hypothyroidism, we present the Apgar scale, which helps in early clinical screening of the disease (Table 18-2).

Table 18-2.Apgar score for diagnosing congenital hypothyroidism in newborns*

* Congenital hypothyroidism should be suspected with a score greater than 5 points.

Given the high prevalence of hypothyroidism, the slight severity of clinical signs of the disease in the first days, weeks of life, as well as serious consequences late diagnosis diseases, since the mid-1970s, in many developed countries of the world, state systems of neonatal screening for congenital hypothyroidism have been gradually introduced.

Screening makes it possible to make a diagnosis in the first days of a child's life, before the development of the clinical picture of the disease, and thus avoid the severe consequences of the disease, the main of which are a delay in the mental and physical development of the child. Economically, the cost of screening correlates with the cost of treating a disabled child in late diagnosed cases as 1:4.

Treatment

Immediately after the diagnosis is established, and also in doubtful cases, it is necessary to start thyroid replacement therapy.

drugs. Levothyroxine sodium is the drug of choice for the treatment of congenital hypothyroidism. It is completely identical to the natural human hormone T 4 - this is its main advantage over other synthetic drugs. In addition, after taking levothyroxine sodium, a “depot” of this drug is created in the blood, which is consumed as needed by deiodinating T 4 and converting it into T 3 . Thus, it is possible to avoid high, peak concentrations of T 3 in the blood.

The entire daily dose should be taken in the morning 30 minutes before breakfast with a small amount of liquid. For small children, the drug should be given during the first morning feeding, in crushed form.

The initial dose of levothyroxine sodium is 12.5-25-50 mcg / day or 10-15 mcg / kg / day. Approximate doses of levothyroxine sodium, which are recommended to prescribe to children for the treatment of congenital hypothyroidism, are shown in Table. 18-3.

Table 18-3.Approximate doses of levothyroxine sodium for the treatment of children with congenital hypothyroidism

The most reliable indicator of the adequacy of the treatment received by the child for hypothyroidism is the normal content of TSH in the blood serum. The concentration of T 4 usually normalizes 1-2 weeks after the start of treatment, and the concentration of TSH - after 3-4 weeks.

With long-term treatment, indicators of the adequacy of the applied dose of levothyroxine sodium are growth dynamics data, the general development of the child, and indicators of skeletal differentiation.

The complex of therapeutic measures for congenital hypothyroidism should include symptomatic therapy(antianemic, antirachitic, vitamin therapy), exercise therapy, massage, according to indications - nootropic drugs.

Forecast

In all children with congenital hypothyroidism, with early and adequate treatment, optimal intellectual development can be achieved.

Diffuse toxic goiter (Graves' disease)

Diffuse toxic goiter is an autoimmune disease characterized by diffuse enlargement of the thyroid gland, the presence of thyrotoxicosis and infiltrative ophthalmopathy.

Thyrotoxicosis is a complex of clinical and metabolic changes resulting from the influence of an increased amount of thyroid hormones on the body. The term "hyperthyroidism" is used when the source of increased secretion of thyroid hormones is the thyroid gland.

ETIOLOGY

Children, especially younger children, may develop diffuse toxic goiter non-immune genesis due to congenital activating mutation of the TSH receptor gene. In older children, as in adults, thyrotoxicosis is often caused by toxic adenoma of the thyroid gland. rare cause diffuse toxic goiter - pituitary adenoma (thyrotropinoma).

PATHOGENESIS

IN thyroid gland thyroid hormones are synthesized - T 4 and T 3, while the former accounts for 90%. Most of the T 3 circulating in the blood comes from peripheral tissues, where it is synthesized from T 4 under the action of local deiodinases. The secretion of thyroid hormones is activated by TSH, and its secretion, in turn, is increased by thyrotropin-releasing hormone of the hypothalamus. TSH receptors are located on the surface of thyroid follicular cells.

Diffuse toxic goiter is an autoimmune disease, which is based on the formation of antibodies to the TSH receptor, the so-called thyroid-stimulating antibodies. The latter, by binding to the TSH receptor, have an effect similar to that of TSH. There is a constant stimulation of the secretion of thyroid hormones without the participation of TSH. In addition, an increased content of thyroid hormones leads to blockade of TSH secretion.

PATHOMORPHOLOGY

Polymorphism of follicles, transition of cubic epithelium to cylindrical, hypertrophy and hyperplasia of thyroid epithelium, sometimes papillary outgrowths in the lumen of follicles are noted. The colloid is usually liquid with vacuolization. Focal, diffuse or combined lymphoid infiltration is observed between the follicles.

CLASSIFICATION

By severity, diffuse toxic goiter is classified as follows.

mild thyrotoxicosis- Heart rate does not exceed 100 per minute, moderate

noe decrease in body weight, there are no signs of damage to other organs and systems.

Thyrotoxicosis of moderate severity- Heart rate from 100 to 150 per minute, pronounced weight loss, lower cholesterol, gastrointestinal disorders, signs of adrenal insufficiency (low diastolic blood pressure, hyperpigmentation).

Severe thyrotoxicosis- Heart rate more than 150 per minute, expressed about

dystrophy up to cachexia, atrial fibrillation, a tendency to atrial fibrillation, with severe thyrotoxicosis, a thyrotoxic crisis often develops.

CLINICAL PICTURE

Goiter

Enlargement of the thyroid gland is the most characteristic sign of diffuse toxic goiter, observed in 100% of children with this disease. When examining a patient, it is necessary to remember about the possibility of a retrosternal location of the thyroid gland, when its true dimensions cannot be estimated and with initial examination goiter may not be diagnosed. Light and moderate forms of diffuse toxic goiter are often accompanied by a slight increase in the thyroid gland. For severe forms, as a rule, the large size of the goiter is characteristic, but the size of the goiter does not always correlate with the severity of thyrotoxicosis.

Skin

In children with thyrotoxicosis, the skin is usually hot and moist. This occurs as a result of the expansion of skin vessels and increased sweating. The most reliable temperature and humidity of the skin can be assessed on the inner surface of the shoulders and hips or on the surface of the chest. The elbows of patients with thyrotoxicosis are smooth and pink. The skin of these patients is easily reddened. The palms resemble "hepatic", there may be telangiectasias. Sometimes hyperpigmentation is observed, which indicates the presence of adrenal insufficiency. Nails can be soft and brittle.

Thyrotoxic ophthalmopathy

Eye changes in patients with diffuse toxic goiter can be both a manifestation of thyrotoxicosis and an autoimmune process.

sa localized in the retrobulbar tissue. A complex of eye symptoms caused by thyrotoxicosis is called thyrotoxic ophthalmopathy, and an autoimmune lesion of retrobulbar tissue and oculomotor muscles- infiltrative ophthalmopathy. As a rule, the clinical signs of thyrotoxic ophthalmopathy subside as the severity of thyrotoxicosis symptoms decreases. Signs of autoimmune or infiltrative ophthalmopathy persist after the elimination of thyrotoxicosis symptoms. The severity of eye symptoms, as well as their dynamics during the treatment of diffuse toxic goiter, are predictive criteria for the effectiveness of conservative therapy for the disease. Clinical signs of ophthalmopathy are observed in 50-93% of patients. However, during MRI, ultrasound of the orbits, signs of oculomotor muscle edema, as well as an increase in the volume of retrobulbar fiber, are found in all patients with diffuse toxic goiter, regardless of the presence of clinical symptoms of ophthalmopathy. Infiltrative ophthalmopathy can also develop in the absence of diffuse toxic goiter.

One of the characteristic symptoms of ophthalmopathy with diffuse toxic goiter in children is exophthalmos (Fig. 18-1 on the insert). Nevertheless, exophthalmos is not considered a mandatory sign of diffuse toxic goiter. According to various authors, the prevalence of exophthalmos in diffuse toxic goiter in children ranges from 52 to 93%. Exophthalmos is usually asymmetrical. Unilateral exophthalmos in children is extremely rare. Periorbital edema may mask manifestations of exophthalmos. Sometimes patients complain of a feeling of pressure behind the eyeballs. Exophthalmos is so pronounced that patients cannot close their eyes during sleep. This symptom is called lagophthalmos. Clinical signs of thyrotoxic ophthalmopathy also include increased photosensitivity, lacrimation, aggravated by the wind, conjunctival injection. Quite often, blurred vision, diplopia, and rapid eye fatigue are noted. Severe ophthalmopathy is often associated with infectious lesions conjunctiva and corneal ulceration. Eye symptoms diffuse toxic goiter are given in table. 18-4.

The degree of exophthalmos can be objectively assessed using an exophthalmometer. This device allows you to measure the distance between the lateral corner of the eye and the most protruding point of the cornea. Normally, it should be no more than 20 mm, and with severe exophthalmos it can reach 30 mm.

Table 18-4.Eye symptoms with diffuse toxic goiter

The cardiovascular system

Cardiovascular disorders are considered the most important symptom of thyrotoxicosis in both adults and children. The most common cardiac symptom of thyrotoxicosis is tachycardia. Often it may precede other signs of the disease. Often, children with thyrotoxicosis complain of palpitations that occur spontaneously or against the background of minimal psychological or physical exertion. When assessing the heart rate in children, it is necessary to remember the age norm. Tachycardia in children with diffuse toxic goiter is permanent and does not go away during sleep and emotional switching of the patient. With an objective examination, an increased cardiac impulse can be diagnosed. Heart sounds are often accentuated, amplified. Severe forms of the disease may be accompanied by muffled heart sounds. Quite often listen to inorganic functional noise. As a rule, these are systolic murmurs at the apex of the heart, above the pulmonary artery, at the Botkin-Erb point. Echocardiography in some patients allows you to determine the signs of left ventricular hypertrophy, which is functional in nature and takes place against the background of compensation for the underlying disease. When studying the metabolism of the heart muscle in patients with diffuse toxic goiter, a decrease in energy resources myocardium, decrease in glycogen content, increased protein catabolism. At the same time, blood flow and oxygen utilization in the myocardium increase. When conducting an ECG in children, an acceleration of atrioventricular conduction is diagnosed, an increase in the voltage of the teeth P, QRS, T sinus

tachycardia. In addition, extrasystole can be determined. Symptoms such as atrial fibrillation and paroxysmal tachycardia, with diffuse toxic goiter in children is rarely observed.

With diffuse toxic goiter, reduced peripheral resistance and increased cardiac output. This leads to an increase in systolic and a decrease in diastolic pressure and, consequently, to an increase in pulse pressure.

Digestive system

In patients with severe thyrotoxicosis, an increase in appetite is often noted. However, despite this, severe forms of thyrotoxicosis in children often lead to weight loss of varying degrees. The frequency of stool increases to several times a day. Diarrhea is rarely seen. Anorexia, nausea, vomiting and abdominal pain are considered rare symptoms of the disease and are noted only in the case of severe forms of thyrotoxicosis. In connection with the increased motility of the gastrointestinal tract, malabsorption syndrome may occur.

Liver dysfunction is noted only in the case of severe forms of thyrotoxicosis. Possible hepatomegaly, jaundice, increased activity of liver enzymes. Hypoxia and increased basal metabolic rate lead to some decrease in glycogen content. In severe thyrotoxicosis, there may be fatty infiltration, local fibrosis, lymphatic infiltration and proliferation of the endothelium of the bile ducts.

Nervous system

Disorders nervous system are often the leading symptoms of thyrotoxicosis in children. Thyrotoxicosis leads to disturbances in the psycho-emotional and motor spheres. Often, the first signs of a disease in a child are changes in behavior noted by parents and peers. Children develop nervousness, emotional lability, tearfulness, severe fatigue, and sleep disturbances. Sudden mood swings, unreasonable outbursts of anger lead to conflicts with parents, friends and teachers. Children often suffer from concentration problems and memory impairment. All this negatively affects the child's academic performance and leads to his social maladaptation. Among motor disorders, hyperkinesis resembling chorea is considered the most characteristic: violent, fast, jerky movements of the fingers, head, contractions of mimic muscles and muscles of the limbs. On examination, the child cannot sit in one place, drums on the table, straightens his hair, fastens and unfastens

buttons. The movements are fast, abrupt, sweeping and often aimless. On examination, a fine tremor of the fingers, tongue and eyelids is determined. However, in children, unlike adults, tremor is observed less frequently and is not considered an early symptom of the disease. At EEG diagnose fast-wave activity. The pathogenetic nature of changes in the nervous system in thyrotoxicosis has not been completely elucidated. It is assumed that neurological disorders may be due to both an increased tone of the sympathetic nervous system and the direct effect of thyroid hormones on the nervous tissue, which has a large number of specific receptors.

Skeletal system

Thyrotoxicosis is characterized by increased excretion of calcium and phosphorus through the intestines and kidneys. In addition, an increased excretion of collagen breakdown products in the urine is noted. All this leads to a decrease in bone density. However, pathological fractures do not occur in children with thyrotoxicosis. In the blood, hypercalcemia is often determined. Serum concentrations of alkaline phosphatase and osteocalcin may also be elevated. The content of PTH in this case is often reduced or is within the normal range.

urinary system

The most common symptom of urinary disorders in children is polyuria, which develops as a result of increased renal blood flow and filtration. Polyuria and disorders of the nervous system often lead to the development of more often nocturnal and sometimes daytime enuresis in a child.

Hematopoietic system

In thyrotoxicosis, an increased activity of erythropoiesis is usually observed. IN peripheral blood the number of erythrocytes increases. Strengthening of erythropoiesis occurs both as a result of the direct effect of thyroid hormones on the bone marrow, and due to increased production of erythropoietin. At the same time, the plasma volume increases, and the hematocrit remains within the normal range. In peripheral blood, leukopenia is often determined due to a decrease in the absolute number of neutrophils, which leads to relative lymphocytosis. In addition, there may be absolute or relative monocytosis and eosinophilia. Splenomegaly is diagnosed in 10% of patients. Often determine generalized lymphadenopathy. It is assumed that splenomegaly and lymphadenopathy are due to a generalized autoimmune process, so

as for non-autoimmune forms of thyrotoxicosis, these changes are not characteristic.

Endocrine system

The effect of thyrotoxicosis on endocrine system most pronounced in relation to the adrenal glands. A number of symptoms reflect adrenal insufficiency, which develops in varying degrees of severity in all children with diffuse toxic goiter. General weakness, fatigue, pigmentation of the skin, low diastolic blood pressure reflect the insufficiency of glucocorticoids. As a result of increased activity 11 b -hydroxysteroid dehydrogenase increases the inactivation of cortisol - the transformation of the 11-hydroxyl group into a keto group. At the same time, the secretion of cortisol also increases, and its concentration in the blood does not change. The content of free cortisol in daily urine may be somewhat elevated. The formation of ACTH by the pituitary gland does not change. Plasma renin activity may be increased. Sensitivity to angiotensin II is reduced. The concentrations of adrenaline and norepinephrine in the blood are within the normal range.

Physical development and bone age in children with thyrotoxicosis, as a rule, are somewhat accelerated, but growth rates rarely go beyond the normal range. Sometimes there may be a delay in sexual development.

On the part of protein metabolism, the predominance of catabolic processes is noted. This increases both the synthesis and the breakdown and excretion of protein from the body. In this regard, a negative nitrogen balance, weight loss, muscle weakness are observed, and there may be a decrease in albumin concentration.

Some patients observe the pathology of carbohydrate metabolism - a violation of glucose tolerance. Plasma insulin levels are usually elevated.

With diffuse toxic goiter, fat metabolism is sharply disturbed. An increase in lipolytic processes leads to a decrease in the content of cholesterol and triglycerides in the blood, as well as to an increase in the concentrations of free fatty acids and glycerol. Weight loss is one of the leading and early symptoms of diffuse toxic goiter in children, although it is not observed in all cases. Sometimes the appetite is so increased that even with a significant increase in the level of basal metabolism, patients do not lose weight.

Complications

The most life-threatening complication of thyrotoxicosis is thyrotoxic crisis. It can be caused by various reasons -

mi, the most common of which is considered to be resection of the thyroid gland against the background of decompensated thyrotoxicosis or in the case when glucocorticoids were not used in the pre- and postoperative period. In addition, the causes of the crisis may be the abolition or inadequate implementation of antithyroid therapy, an infectious disease, mental trauma, severe physical exertion, surgery outside the thyroid gland. Pathogenesis thyrotoxic crisis First of all, it comes down to a sharp increase in the release of thyroid hormones into the blood. Against this background, signs of relative adrenal insufficiency increase, as thyroid hormones increase the metabolism of cortisol. Against the background of the crisis, the need for glucocorticoids in peripheral tissues increases, which increases the relative adrenal insufficiency. The crisis, as a rule, develops within a few hours, less often - gradually, over several days. Excitation and tachycardia increase, arrhythmia occurs, body temperature rises, systolic blood pressure rises, diastolic blood pressure decreases. With the further development of the crisis, a decrease in both systolic and diastolic blood pressure is noted, signs of heart failure increase. Patients may have insomnia, vomiting, diarrhea, increased sweating, a feeling of fear, a sharp headache, oliguria, facial flushing, frequent breathing, suffocation, sudden motor anxiety, erratic movements, which are replaced by adynamia, apathy, stupor, turning into a coma.

ultrasoundthyroid gland allows you to evaluate its size, as well as its structure. Changes in the structure of the thyroid gland in diffuse toxic goiter are reduced to a sharp decrease in echogenicity (Fig. 18-2 on the insert) and the appearance of an uneven structure. These structural changes are not strictly specific for diffuse toxic goiter, and therefore they can be determined with other autoimmune diseases thyroid gland, such as autoimmune thyroiditis.

Radioisotope research thyroid in children is rarely used. Scintigraphy is performed mainly for suspected toxic adenoma of the thyroid gland, it also allows you to identify functioning metastases of well-differentiated thyroid cancer, which may be the cause of thyrotoxicosis.

Study of the immunological status allows you to determine the increase in the titer of non-specific, as well as specific antibodies. Specific for diffuse toxic goiter AT to the TSH receptor.

By binding to the TSH receptor, they activate the production of thyroid hormones. Preservation of elevated titers of antibodies to TSH receptors against the background of compensation for the disease is a prognostically unfavorable indicator of relapse. AT to thyroglobulin, microsomal Ag are not strictly specific for diffuse toxic goiter. Elevated titers of these antibodies are also possible in other autoimmune thyroid diseases.

Study of hormonal status. Determining the concentrations of TSH, T 3 and T 4 allows you to confirm the presence of hyperthyroidism with a high probability. The content of TSH in diffuse toxic goiter is always reduced. The basal concentration of T 3 is often increased to a greater extent than the concentration of T 4 . An increase in the content of TSH in combination with elevated concentrations of thyroid hormones makes it possible to suspect central thyrotoxicosis.

Biochemical research blood indicates a decrease in cholesterol, may be hyperglycemia. When conducting a load test with glucose, a violation of carbohydrate tolerance is determined.

Visual palpation assessment sizes of the thyroid gland are produced according to the WHO classification (1994):

0 degree - no goiter;

1 degree - palpable goiter;

II degree - visible goiter (Fig. 18-3 on the insert).

On examinationevaluate the symptoms of compression of the neck organs. Dysphonia, paresis of the vocal cords are attributed to signs of compression of the recurrent nerve; cough, hiccups, bradycardia - vagus nerve. Difficulty swallowing occurs with compression of the esophagus, but this symptom can also be observed with increased nervous excitability. To confirm the compression of the esophagus, radiopaque examination with barium sulfate helps. Bernard-Horner syndrome (ptosis, miosis, enophthalmos), hyperemia of half of the face, as well as sympathoadrenal crises are noted with compression of the nerve ganglia. Severe compression of the trachea leads to stridor. The initial signs of compression of the trachea are easily diagnosed with ultrasound.

Most often, at puberty, diffuse toxic goiter has to be differentiated from SVD, the thyrotoxic phase of autoimmune thyroiditis, less often from toxic thyroid adenoma, TSH-secreting pituitary adenoma, resistance to thyroid hormones.

SVD- a fairly common disease, especially often observed in adolescence. With SVD, there may be tachycardia

diah, sweating, tremor, changes in blood pressure - these symptoms resemble the clinical picture of diffuse toxic goiter. Goiter in these cases does not serve as a differential diagnostic sign due to the fact that in iodine-deficient regions it is considered a fairly common phenomenon. However, the clinical signs of SVD have their own characteristics: tachycardia is transient, stops during sleep, when the child's attention is switched in a conversation, it is often accompanied by respiratory arrhythmia. With diffuse toxic goiter, tachycardia is constant, does not depend on sleep and wakefulness, does not change with inhalation and exhalation. Sweating in SVD is often regional (they note increased humidity of the palms, feet, axillary areas), with diffuse toxic goiter, the increase in humidity and sweating is diffuse. The skin temperature in patients with SVD is normal, the palms and feet are often cold and moist. With diffuse toxic goiter, the skin is intensely warm or even hot. Hand tremors are often noted in patients with SVD, but the tremor is large, sweeping, and inconsistent. With diffuse toxic goiter, the tremor is small, constant, and the so-called telegraph pole symptom can be observed. The hormonal profile will help to finally confirm the diagnosis of diffuse toxic goiter in these cases: a decrease in the content of TSH, an increase in the concentrations of T 4 and T 3 .

Autonomous toxic adenoma of the thyroid gland V childhood observed extremely rarely. Among patients with toxic adenomas, children and adolescents make up only 2.2 to 8.6%. In all age groups, female patients predominate. The pathogenesis of toxic adenoma remains unclear to the end. Recently, it has become known about mutations in the TSH receptor gene, which are determined in thyroid adenomas. Most toxic adenomas are larger than 3 cm in diameter. With clinically pronounced thyrotoxicosis, a decrease in the concentration of TSH and an increase in the content of T 4 are detected. In some cases, the adenoma secretes predominantly T 3 , especially in conditions of iodine deficiency. In the absence of clinical signs of thyrotoxicosis, hormonal analysis helps to diagnose subclinical thyrotoxicosis: the concentrations of TSH, free and total T 4 are within the normal range, the content of T 3 is increased, and an increased TSH response to thyroliberin stimulation is also noted. Solitary toxic adenomas are usually benign. However, among cases of autonomous toxic tumors, malignant carcinomas have also been described, including those in childhood. The frequency of malignant toxic carcinomas is not high, since even highly differentiated carcinomas, as a rule, have a low ability to synthesize thyroid hormones.

Toxic adenomas can sometimes be diagnosed by palpation of the thyroid gland. The presence of thyroid adenoma is confirmed by ultrasound and scanning of the thyroid gland with radioactive iodine. In the case of a toxic adenoma, it is indicated surgical treatment- adenomectomy, and when determining carcinoma, the scope of the operation is expanded to subtotal or total resection of the thyroid gland.

Thyroiditis.Clinical signs of thyrotoxicosis are also observed in various types of thyroiditis: chronic (chronic autoimmune thyroiditis, Hashimoto's goiter), as well as acute and subacute. In most patients with chronic autoimmune thyroiditis, thyroid hormone activity may be reduced or within the normal range. In total, 5-10% of children and 6% of adults with chronic autoimmune thyroiditis develop a clinical picture of thyrotoxicosis. It is assumed that thyrotoxicosis in the early phase of the disease may be caused by the influence of thyroid-stimulating antibodies or by lysis of thyroid cells and the release of thyroid hormones into the bloodstream. Thyrotoxicosis, which develops in chronic autoimmune thyroiditis, is not severe. In the phase of thyrotoxicosis, the differential diagnosis of diffuse toxic goiter and chronic autoimmune thyroiditis is very difficult. In the study of the immunological status in both cases, positive thyroid-stimulating antibodies, antibodies to microsomal antigen and thyroglobulin are determined, so these indicators cannot serve as a differential diagnostic sign. With both diseases, ophthalmopathy is possible. The ultrasound picture is also nonspecific. An increase in volume, a decrease in echogenicity and an uneven structure can be both in chronic autoimmune thyroiditis and in diffuse toxic goiter. Radioscintigraphy in chronic autoimmune thyroiditis reveals uneven capture of the radiopharmaceutical, in diffuse toxic goiter - signs of increased thyroid function. However, the results of this study are not specific, and it is unsafe, especially in children. The most characteristic differential diagnostic sign is the dynamics of thyrotoxicosis: in the case of chronic autoimmune thyroiditis, the thyrotoxic phase fairly quickly (within a few months) spontaneously passes into hypothyroidism. This happens especially quickly when thyreostatic drugs are prescribed.

The classic signs of acute thyroiditis include chills, hyperthermia, reddening of the skin in the neck, tenderness of the thyroid gland on palpation and its asymmetric enlargement. Signs of thyrotoxicosis are observed in 2.5% of children.

Iodine-induced thyrotoxicosis occurs with increased consumption of iodine, which leads to an increase in the synthesis of T 3 and T 4 . He raz-

develops in patients with autonomy of the thyroid gland caused by chronic iodine deficiency or autonomic adenomas that have arisen against the background of diffuse toxic goiter. It is assumed that the intake of a large amount of iodine disrupts autoregulatory processes in the thyroid gland. The Wolf-Chaikoff phenomenon, which occurs in a normal thyroid gland, when an excess intake of iodine leads to blockade of the synthesis of thyroid hormones, has been well studied. In the case of iodine-induced thyrotoxicosis, on the contrary, there is an increase in the secretion and synthesis of thyroid hormones. Excessive intake of iodine can be due to the use of biologically active food additives, local antiseptics, radiopharmaceuticals, medicines (amiodarone) containing iodine. In the study of hormonal status, a significant increase in the concentration of T 4 is determined. At the same time, the content of T 3 is slightly increased or within the normal range, the ratio of concentrations of T 4 /T 3 is increased. Treatment of iodine-induced thyrotoxicosis primarily requires the cessation of iodine intake. An overdose of thyroid hormones in children in some cases can lead to clinically significant thyrotoxicosis.

Thyrotoxicosis of non-autoimmune origin - a rare disease that is caused by a mutation in the TSH gene. The TSH receptor belongs to the family of G protein-coupled transmembrane receptors. The structure of the TSH gene is encoded by a gene located on chromosome 14. Studies have identified three activating mutations in the TSH receptor gene in patients with congenital non-autoimmune thyrotoxicosis. The identified mutations cause conformational changes in the transmembrane regions of the receptor, which leads to the activation of the receptor in the absence of the influence of TSH. The mechanism of spontaneous intracellular activation also leads to hyperplasia and hypertrophy of thyrocytes and, consequently, to the development of goiter. In a newborn with clinical signs of thyrotoxicosis, the presence of an activating mutation in the TSH receptor gene can be assumed if the mother does not have thyroid disease. In the study of hormonal status, an increase in the concentrations of T 3 , T 4 , a decrease in the content of TSH, thyroid-stimulating antibodies are absent. The manifestation of congenital non-autoimmune thyrotoxicosis in the prenatal period can lead to serious consequences; therefore, prenatal diagnosis is extremely important.

TREATMENT

Treatment begins with the use of thyreostatic drugs andβ - adrenoblockers. Usageβ -adrenoblockers at the first stages of treatment of the disease allows to achieve rapid clinical

effect: the child becomes calmer, heart rate, sweating, tremor decrease. From the group of β-blockers, propranolol is used at a dose of 1 mg / kg / day every 6-8 hours.

Antithyroid drugs are prescribed simultaneously with β-blockers. In children, antithyroid drugs are used thiamazole and propylthiouracil. These drugs are similar in mechanism of action and efficacy, as well as in the frequency and severity of side effects. The mechanism of action of antithyroid drugs is to inhibit the attachment of iodine to tyrosine residues in thyroglobulin, as well as blocking the attachment of iodotyrosine residues to T 4 and T 3 . In addition, propylthiouracil inhibits the peripheral conversion of T 4 to T 3 . Clinical data regarding the immunosuppressive effect of antithyroid drugs are conflicting. Antithyroid therapy is usually started with maximum dose: 0.5-0.7 mg/kg/day with thiamazole and 5-7 mg/kg/day with propylthiouracil. Usually after 3-4 weeks, and in severe thyrotoxicosis after 6 weeks, β-blockers are canceled and, with persistent euthyroidism, they begin to reduce the dose of thyreostatics (thiamazole) according to the following scheme: once a week, reduce the daily dose by 5 mg; when it reaches 10 mg, it continues to be reduced by 2.5 mg per week. The maintenance dose of thiamazole is 2.5-5 mg / day and does not change during 2-3 years of therapy.

In cases where the use of thyreostatics leads to a complete blockade of the thyroid gland, levothyroxine sodium is added to the therapy of diffuse toxic goiter. Signs of reblocking of the thyroid gland include an increase in the volume of the gland (according to ultrasound data) in the absence of signs of recurrence of thyrotoxicosis (goiter effect); bradycardia, edema, constipation (clinical signs of hypothyroidism), an isolated increase in TSH content or in combination with a decrease in the concentration of free T 4 . In this case, as a rule, the first sign of a reblocking of the thyroid gland is an increase in the concentration of TSH. In the event that it is possible to diagnose an isolated increase in the concentration of TSH, then you can start by reducing the dose of thyreostatics.

Side effects of antithyroid drugs are more common in children than in adults. The most frequently diagnosed leuko- and thrombocytopenia, toxic hepatitis, less often - lymphadenopathy, polyneuropathy, allergic skin reactions.

With the development side effects replace the drug. In cases where the replacement of the drug does not improve the condition, surgical treatment is indicated.

Therapeutic tactics often leads to relapses of thyrotoxicosis. Persistent and long-term remission can be achieved in 30-60%

children receiving conservative treatment. The criteria for complete recovery include normalization of the size of the thyroid gland, persistent (within two years) clinical and hormonal euthyroidism, as well as normalization of the titer of antithyroid antibodies.

Indications for surgical intervention - the absence of a stable and long-term remission of thyrotoxicosis against the background of adequate therapy, a large goiter with signs of compression of the neck organs, nodulation, retrosternal goiter, failure to follow the doctor's recommendations, the inability to avoid complications of antithyroid therapy, the manifestation of diffuse toxic goiter during pregnancy, severe ophthalmopathy. The scope of the operation: subtotal, subfascial resection of the thyroid gland.

PREVENTION

Given the autoimmune nature of the disease, prevention of acute and chronic infectious diseases is necessary. Specific preventive measures have not been developed.

FORECAST

Conservative treatment leads to recovery in 30-50% of cases. In more than half of the cases, a relapse of the disease is observed. Correctly performed surgical treatment (total thyroidectomy) leads to the elimination of diffuse toxic goiter, but the child develops hypothyroidism, requiring lifelong replacement therapy with levothyroxine sodium.

Adrenal insufficiency

Adrenal insufficiency (hypocorticism) is a symptom complex caused by reduced production of hormones of the adrenal cortex. According to the level of damage, primary adrenal insufficiency is distinguished, associated with the pathology of the adrenal gland itself, secondary, associated with reduced secretion of ACTH, and tertiary, caused by a violation of the secretion of corticotropin-releasing hormone or other factors that stimulate the production of ACTH. The last two forms are also called central.

Symptoms of adrenal insufficiency are not specific and can be hidden under the guise of various diseases. Weakness, fatigue, poor appetite, low weight gain in young children, and weight loss in older children are characteristic of many diseases. Nausea, repeated vomiting, loose stools, abdominal pain are regarded as manifestations of intestinal infections. In newborns and young children,

Hypoglycemia can be a sign of adrenal insufficiency. Severe hyperpigmentation does not always accompany even primary adrenal insufficiency. Given the absence of a specific clinical picture, adrenal insufficiency is rarely diagnosed before the development of salt-wasting crises that are life-threatening for the patient. With timely diagnosis, adrenal insufficiency is successfully compensated by replacement therapy.

Etiology

Previously, tuberculosis of the adrenal glands was considered the most common cause of primary hypocorticism. Until now, in some regions of the world, adrenal insufficiency of tuberculosis etiology ranks second after autoimmune damage among adults and older children. Hypocorticism in young children is more often associated with abnormalities in the development of the adrenal glands and congenital disorders of steroidogenesis. There are 3 groups of causes of primary adrenal insufficiency.

Congenital malformations of the adrenal glands:

Congenital adrenal hypoplasia;

Defective steroidogenic factor 1;

Resistance to ACTH;

Familial glucocorticoid deficiency type I and II;

Allgrove's syndrome (syndrome 3A).

Destruction of the adrenal glands:

Autoimmune genesis (autoimmune polyglandular syndromes);

Adrenoleukodystrophy;

Hemorrhages in the adrenal glands;

Metastatic lesion of the adrenal glands;

Infectious lesions of the adrenal glands (including tuberculosis);

Amyloidosis.

Congenital disorders of steroidogenesis:

Congenital dysfunction of the adrenal cortex;

Mitochondrial diseases;

Deficiency of cholesterol metabolism enzymes;

Smith-Lemli-Opitz syndrome.

The relative frequency of various nosological forms varies depending on the gender and age of patients.

At birth, adrenal hemorrhage due to hypoxia or sepsis is the most common cause of acute adrenal insufficiency.

In the neonatal period and at a young age, the first place among the causes of hypocorticism is occupied by various forms of congenital dysfunction of the adrenal cortex in children of both sexes and congenital adrenal hypoplasia in boys.

In the older age group, as in adults, the most common autoimmune polyglandular syndrome and adrenoleukodystrophy. With age, the proportion of infectious and metastatic lesions of the adrenal glands increases.

Central forms of hypocorticism are caused by deficiency of corticotropin-releasing hormone and/or ACTH. All the causes that cause secondary and tertiary adrenal insufficiency can be divided into 3 groups.

Congenital secondary hypocorticism:

Isolated ACTH deficiency;

Congenital hypopituitarism.

Destruction of the hypothalamic-pituitary structures:

Tumors of the central nervous system;

Traumatic brain injury;

infiltrative processes;

Infectious defeat;

Surgical intervention;

Irradiation of the head.

Iatrogenic suppression of the hypothalamic-pituitary-adrenal

systems with exogenous glucocorticoids.

Pathogenesis

Primary adrenal insufficiency

In primary adrenal insufficiency, the secretion of all 3 groups of adrenal hormones drops out: glucocorticoids, mineralocorticoids and androgens (depending on the form). Since gluco- and mineralocorticoids are involved in maintaining homeostasis, protein, carbohydrate, fat and water-electrolyte metabolism, their deficiency causes numerous disorders.

Cortisol is actively involved in carbohydrate metabolism, acting as an insulin antagonist. With a deficiency of cortisol, glycogen synthesis in the liver, gluconeogenesis decrease and the sensitivity of peripheral tissues to insulin increases. All of the above leads to the development of hypoglycemia. The likelihood of developing hypoglycemia increases with a concomitant deficiency of catecholamines or insufficient secretion of growth hormone, characteristic of some forms of adrenal insufficiency.

Aldosterone deficiency leads to severe cardiovascular disorders. A decrease in sodium reabsorption and an increase in potassium reabsorption in the kidneys lead to hyponatremia, hypokalemia, a decrease in BCC and, as a result, to the development of arterial hypotension up to shock. The situation is exacerbated by hyperkalemia, which causes disturbances heart rate and myopathy. Glucocorticoid deficiency contributes to the development of arterial hypotension, possibly as a result of a decrease in the sensitivity of the vascular wall to angiotensin and norepinephrine, and also as a result of an increase in the synthesis of PgI 2 . Reduced sodium reabsorption in the intestine causes dyspeptic disorders such as abdominal pain, malabsorption.

A deficiency of adrenal androgens contributes to an increase in catabolic processes and leads to an increase in the level of residual nitrogen. Due to insufficient secretion of adrenal androgens in children, delayed adrenarche is noted.

In primary adrenal insufficiency, low levels of cortisol by a negative feedback mechanism lead to an increase in the concentrations of corticotropin-releasing hormone, ACTH and other proopiomelanocortin derivatives. In turn, high concentrations of ACTH, melanocyte-stimulating hormone, acting on melanocyte receptors, cause an increase in melanin synthesis, which is manifested by the clinical picture of hyperpigmentation.

Secondary and tertiary adrenal insufficiency

In terms of pathogenesis, the hallmarks of the central forms of hypocorticism include the absence of mineralocorticoid deficiency and hyperpigmentation. Since the regulation of aldosterone synthesis is under the control of the renin-angiotensin system and only to a small extent depends on the content of ACTH, there are no symptoms of salt loss in patients with central hypocorticism. The decrease in the concentration of ACTH and other proopiomelanocortin derivatives explains the absence of hyperpigmentation in secondary and tertiary adrenal insufficiency.

Clinical picture

The time of onset of the first symptoms, as well as the clinical symptoms of adrenal insufficiency themselves, depends on the etiological factor.

In adrenal dysgenesis, impaired steroidogenesis and pseudohypoaldosteronism, signs of the disease appear soon after birth and are primarily associated with salt loss, i.e. with mineralocorticoid deficiency. Patients report persistent vomiting

"fountain", an increase in malnutrition, there are signs of dehydration up to the development of vascular collapse. In the absence of replacement therapy, such patients die in the neonatal period.

In older children, the main cause of hypocorticism is the destructive process in the adrenal glands. In this case, the clinical picture develops gradually, as the cells of the adrenal cortex die. The first clinical symptoms occur only after the destruction of more than 90% of all cells. Initially, patients complain about fatigue, muscle weakness, loss of appetite, postural dizziness. Patients do not tolerate physical activity, but their well-being improves in a horizontal position. When not timely diagnosis and left untreated, these patients may develop a salt-wasting crisis. The first symptoms of acute adrenal insufficiency are nausea, vomiting, loose stools, abdominal pain, arterial hypotension. Quite quickly, dehydration and shock subsequently develop.

In patients diagnosed with adrenal insufficiency receiving treatment with glucocorticoids and mineralocorticoids, salt-losing crises can develop with the addition of infections, major injuries, or surgical interventions without appropriate correction of therapy. In some children, emotional stress can provoke the development of an adrenal crisis. Taking drugs that accelerate the metabolism of cortisol (levothyroxine sodium, barbiturates) can also lead to decompensation of the disease.

A characteristic sign of primary adrenal insufficiency is hyperpigmentation, which develops as a result of an increase in the concentration of ACTH. Often, people around for the first time notice hyperpigmentation in open areas of the body (face, hands). The maximum development of hyperpigmentation is observed on the skin of the external genital organs, axillary areas, knees, elbows, the nipples, navel, perianal region and scars at the site of skin damage are also pigmented. Areas of hyperpigmentation may be on the mucous membranes of the oral cavity.

The first sign of adrenal insufficiency in children may be hypoglycemia. Hypoglycemia may be accompanied by ketosis, which leads to the diagnosis of ketotic hypoglycemia. Many children are prescribed anticonvulsant therapy without recognizing the hypoglycemic origin of seizures. The development of hypoglycemia is especially characteristic of familial glucocorticoid insufficiency and central forms of hypocorticism (secondary and tertiary adrenal insufficiency).

With central forms of hypocorticism, hyperpigmentation never occurs, since the concentration of ACTH is always low. Mineralocorticoid deficiency is not characteristic of secondary and tertiary adrenal insufficiency and, therefore, there will be no symptoms of salt loss in such patients. Other clinical signs are common for primary, secondary and tertiary adrenal insufficiency.

Laboratory and instrumental research

Laboratory confirmation of the diagnosis of adrenal insufficiency is electrolyte disturbances (hyponatremia, hyperkalemia) and data from hormonal studies: a decrease in the concentration of basal cortisol, aldosterone and an increase in plasma renin activity. It should be clarified that the study of the concentrations of cortisol and aldosterone is uninformative in the most common cause of hypocorticism in the neonatal period - congenital dysfunction of the adrenal cortex (insufficiency of 21-hydroxylase). High levels of cortisol precursors due to cross-reactions in the assays used can give falsely high concentrations of cortisol and aldosterone. If congenital dysfunction of the adrenal cortex is suspected, it is necessary to investigate the content of intermediate products of steroidogenesis characteristic of each of the forms of this disease (see the section "Congenital dysfunction of the adrenal cortex").

Determination of the concentration of basal cortisol

When examining older children with suspected hypocorticism, the first step should be to determine the concentration of basal cortisol in the blood plasma. This study should be carried out early in the morning at 6.00-8.00 hours, which corresponds to the physiological peak of glucocorticoid secretion. Plasma cortisol concentration less than 80 nmol/l confirms the presence of hypocorticism, 80-150 nmol/l is suspicious for hypocorticism, more than 500 nmol/l excludes hypocorticism.

A study of the content of free cortisol in daily urine may be more informative, since in this case the integral secretion of cortisol will also be assessed.

Simultaneously with determining the concentration of cortisol, it is necessary to examine the content of blood electrolytes and plasma renin activity, which serve as laboratory criteria for mineralocorticoid deficiency.

Stimulation test with ACTH

If adrenal insufficiency is suspected, the next step in the diagnosis should be a stimulation test with ACTH.

A short test with ACTH is generally accepted. Initially, blood is taken to determine the concentration of cortisol, after which 250 µg of tetracosactide (a synthetic analog of ACTH) is administered intravenously in 5 ml of 0.9% sodium chloride solution, the duration of the infusion is 2 minutes. Then, after 30 and 60 minutes, blood is taken to re-determine the concentration of cortisol. Normally, the content of cortisol on stimulation exceeds 500 nmol / l. In primary adrenal insufficiency, the response to stimulation is absent or reduced, the cortisol concentration is less than 500 nmol / l. In secondary adrenal insufficiency, in most patients, the reaction to ACTH is absent or reduced. The exception is patients with recently developed central hypocorticism.

In the absence of short-acting ACTH preparations, it is possible to conduct a similar test with prolonged forms of tetracosactide (Sinakten-depot). After intramuscular administration of 1 ml of the drug, blood is taken to determine the concentration of cortisol after 10 and 24 hours. The results are evaluated similarly to the results of the short-acting ACTH test.

The above methods of research allow you to confirm the presence of adrenal insufficiency in a patient. The next step is to differentiate primary adrenal insufficiency from central forms. For this purpose, a study of the basal concentration of ACTH in the blood plasma is shown.

Determination of the basal concentration of ACTH

In primary adrenal insufficiency, the ACTH concentration exceeds 100 pg/ml, while in secondary adrenal insufficiency, the ACTH content is reduced or within the normal range.

Diagnosis and differential diagnosis

In neonates and young children, primary adrenal insufficiency has striking clinical features due to the rapid progression of symptoms of salt loss in combination with hyperpigmentation. Of great help in the diagnosis of hypocorticism in this group of children is a detailed clarification of the family history and the presence of concomitant pathology characteristic of various nosological forms (repeated cases of the disease in the family, early death of children in infancy with a similar clinical picture).

Treatment

Replacement therapy is carried out with gluco- and mineralocorticoids (depending on the form).

Replacement therapy with glucocorticoids

The drug of choice in children is hydrocortisone, an analogue of the natural adrenal hormone cortisol. The physiological secretion of cortisol in children and adolescents averages 6-8 mg/m2/day. The dose of replacement therapy with hydrocortisone, taking into account absorption and metabolic bioavailability when taken orally, will be 10-12 mg / m 2 / day, evenly divided into three doses.

The individual need for this drug in different patients ranges from 5 to 20 mg/m 2 /day. The selection of an adequate dose of glucocorticoids is carried out primarily on the basis of the clinical picture. With an insufficient dose of hydrocortisone, patients have weakness, hyperpigmentation, postural arterial hypotension, increased sensitivity to infectious diseases, and, in addition, there is a risk of developing nocturnal hypoglycemia. Signs of an overdose of glucocorticoids include inhibition of growth and skeletal maturation, excessive weight gain, the appearance of stretch marks on the skin, increased blood pressure and osteoporosis. Many side effects can be avoided by replacing the short-lived hydrocortisone with a long-acting drug (prednisolone, dexamethasone). The laboratory criterion for the adequacy of the dose of glucocorticoids is the normalization of the concentration of ACTH in the blood serum.

Replacement therapy with mineralocorticoids

Therapy with mineralocorticoids is carried out in patients with primary adrenal insufficiency and isolated hypoaldosteronism. Assign the drug fludrocortisone at a dose of 0.05-0.2 mg / day. As in the case of glucocorticoids, it is necessary to be guided in the selection of the dose of replacement therapy on the clinical picture. With a lack of mineralocorticoids, patients have low blood pressure, increased need in salt, tachycardia, in infants - regurgitation. Laboratory criteria for mineralocorticoid deficiency will be an increase in renin concentration and a tendency to hyperkalemia. Symptoms of an overdose of the drug include arterial hypertension, bradycardia, growth retardation and suppression of plasma renin activity. An increase in the dose of fludrocortisone may be required in the summer in patients living in hot climates, due to the fact that aldosterone deficiency leads to increased excretion of sodium through the sweat glands. Infants in addition to mineralocorticoids, it is usually necessary to add sodium chloride or table salt to food (1-2 g / day).

Endogenous secretion of cortisol in healthy people is increased in cases of intercurrent diseases and surgical interventions.

Patients with adrenal insufficiency need to increase the dose of glucocorticoids by 2-3 times evenly during the day in case of an infectious disease with fever or during traumatic medical procedures (tooth extraction, FEGDS, preventive vaccinations). If oral administration of drugs is not possible, intramuscular or intravenous administration high dose hydrocortisone. The dose of mineralocorticoids is left unchanged.

The key to successful treatment of adrenal insufficiency is to educate the patient and his parents about the rules for adjusting the dose of drugs. Each patient must have an identification card with him indicating the diagnosis, the therapy received and the telephone number of the medical institution where he is being observed.

Adrenal crisis therapy

With decompensation of the disease in patients with hypocorticism, therapeutic measures should be started immediately. First of all, the doctor's efforts should be aimed at correcting water and electrolyte disorders. Massive infusion therapy is carried out with solutions of sodium chloride 0.9% and glucose 5-10% at the rate of 450 ml / m 2 during the first hour, then 3000 ml / m 2 / day. At the same time, hydrocortisone is administered intravenously at a dose of 2-5 mg/kg every 4 hours. After reaching a stable state and correcting electrolyte disturbances, the patient is transferred to oral hydrocortisone and fludrocortisone is added to therapy.

Forecast

With timely diagnosis and adequate treatment, it is possible to achieve normal duration and quality of life.

ACUTE ADRENAL INSUFFICIENCY

Acute adrenal insufficiency, or Addisonian crisis, is an urgent, life-threatening condition characterized by hemodynamic and metabolic disorders against the background of a sharp decrease in the concentration of adrenal cortex hormones (gluco- and mineralocorticoids).

Etiology

Acute adrenal insufficiency can be caused both by a primary lesion of the adrenal glands, and by disorders of the hypothalamic-pituitary-adrenal regulation (deficiency of corticotropin-releasing hormone or ACTH after surgical interventions in the hypothalamic-pituitary region, with pituitary dwarfism).

Often, an adrenal crisis is attributed to the debut of a previously unidentified chronic adrenal insufficiency, which manifested itself in a stressful situation for the body. In patients suffering from chronic adrenal insufficiency of any etiology, acute decompensation of the disease may occur with the development of an adrenal crisis against the background of inadequate replacement therapy, acute intercurrent diseases, surgical interventions, and stress.

However, there are also reasons for the sudden development of destruction of the adrenal cortex, which include thromboembolism, thrombosis of the adrenal veins, hemorrhagic infarction, septic necrosis, and toxic damage. Risk factors for the development of acute adrenal insufficiency include surgery, burn injuries, sepsis of any etiology, massive anticoagulant therapy, and coagulopathy of various origins. Waterhouse-Friderichsen syndrome has been described as bilateral adrenal hemorrhage associated with meningococcemia. The high-risk group includes patients with chronic diseases accompanied by coagulopathy (SLE, hemorrhagic vasculitis, APS, etc.).

Patients receiving high therapeutic doses of glucocorticoids may also develop acute adrenal insufficiency with sudden withdrawal or a sharp decrease in the dose of drugs. The iatrogenic causes of adrenal crisis include complications in the treatment of hypercortisolism (Itsenko-Cushing's disease or syndrome): after adrenalectomy or adenomectomy, as well as during drug therapy with steroidogenesis blockers (aminoglutethimide, ketoconazole, mitotane).

Clinical picture

The clinical picture of acute adrenal insufficiency does not depend on the causes of its occurrence. Moreover, its symptoms are nonspecific and common to many emergency conditions, which greatly complicates timely diagnosis in an urgent situation.

Hemodynamic disorders are characterized by severe arterial hypotension up to vascular collapse, tachycardia, acrocyanosis, anuria. Repeated vomiting, loose stools, and abdominal pain mimic the symptoms of "acute abdomen" or PTI. Neurological disorders, including headache, meningeal symptoms, convulsions, acute psychosis, supor and coma, can be due to both intercurrent or underlying illness, and hypoglycemia as a result of acute glucocorticoid deficiency.

None of these symptoms are strictly pathognomonic for acute adrenal insufficiency. They can be present in any combination and expressed in varying degrees.

Diagnostics

Clinical diagnosis of acute adrenal insufficiency in the absence of indications in the history of chronic disease adrenal glands is often difficult in a critical situation, so it is necessary to carefully ask the patient or his relatives about possible risk factors for the development of an adrenal crisis.

Laboratory diagnostics in an emergency, requiring immediate correction, is also very limited. The main laboratory markers include an increased content of potassium, low concentrations of sodium and blood glucose. Blood samples for the study of cortisol, ACTH and plasma renin activity should be taken, but therapy should be started without waiting for the results.

ECG changes reflect metabolic disorders, in particular hyperkalemia, and are represented by a high T wave, slowing of atrioventricular conduction with an expansion of the P wave, prolongation of the interval S-T and expansion of the complex QRS.

Treatment

Treatment of acute adrenal insufficiency must begin immediately at the slightest suspicion of its presence. Given the high mortality in the first day from the onset of the development of an adrenal crisis and the reversibility possible complications from massive short-term therapy with glucocorticoids, do not be afraid of overdiagnosis.

The catheter should be placed immediately central vein to provide conditions for intravenous infusions. After taking blood samples for biochemical and hormonal studies, it is immediately necessary to begin the introduction of glucocorticoids and 0.9% sodium chloride solution in order to correct hemodynamics. Among glucocorticoid drugs, preference is given to hydrocortisone. First, 100 mg of hydrocortisone is injected intravenously, then, under the control of the content of potassium, sodium and blood pressure, drip administration of hydrocortisone should be continued. The dose of hydrocortisone can reach up to 1000 mg on the first day of treatment. The introduction of mineralocorticoids is considered inappropriate due to the mineralocorticoid activity of hydrocortisone. In addition, the oil solution of deoxycortone ("Deoxycorticosterone") realizes its effect only a few hours after intramuscular injection. Therapy

glucocorticoids are carried out against the background of massive rehydration. During the first day, from 2 to 3 liters of 0.9% sodium chloride solution can be administered under the control of hemodynamic parameters and electrolytes.

Given the high likelihood of hypoglycemia, the treatment regimen includes the introduction of a 5-20% glucose solution, if possible, under the control of its content in the blood plasma.

Depending on the etiology of acute adrenal insufficiency, the underlying disease is treated (antibiotic therapy, etc.).

Mortality as a result of an adrenal crisis is about 50% and falls on the first day of the disease.

After stabilization of the condition, parenteral administration of glucocorticoids and 0.9% sodium chloride solution should be continued for several days under the control of hemodynamic parameters and electrolytes. Then gradually reduce the dose of glucocorticoids and switch to oral administration of drugs, supplementing with replacement therapy with mineralocorticoids (fludrocortisone) in replacement doses. Next, it is necessary to clarify the presence of chronic adrenal insufficiency and move on to permanent adequate replacement therapy.

Prevention

Main task primary prevention Addisonian crisis, and consequently, mortality in the group of patients with chronic adrenal insufficiency is timely adequate therapy of the underlying disease. It is necessary to carry out regular medical monitoring of the adequacy of replacement therapy. A huge role is played by the training of patients and their families in self-control, the rules of behavior in various situations that potentially provoke the development of an adrenal crisis. With intercurrent diseases, injuries, surgical interventions, stress, the dose of glucocorticoids should be increased by 2 times, followed by a gradual return to the previous replacement dose. In world practice, it is recommended to wear special bracelets, which reflect information about the patient's illness and the main points of emergency care: the introduction of glucocorticoids, emergency hospitalization for further qualified medical care.

ISOLATED MINERALOCORTICOID

FAILURE

Isolated hypoaldosteronism in the absence of deficiency of other hormones of the adrenal cortex is manifested by the clinical picture

salt loss. With this pathology, unlike other forms of adrenal insufficiency, the hypothalamus-pituitary-adrenal system is intact. A decrease in the concentration of aldosterone leads to an increase in the activity of only the renin-angiotensin system.

There are 3 groups of isolated mineralocorticoid insufficiency:

Congenital primary hypoaldosteronism.

Acquired secondary aldosterone deficiency.

Pseudohypoaldosteronism.

Congenital primary hypoaldosteronism

Congenital primary hypoaldosteronism is a rare autosomal recessive pathology characterized by salt loss syndrome and delayed physical development. This disease is caused by a violation of the biosynthesis of aldosterone due to a deficiency of the enzyme aldosterone synthase. Unlike deficiency of other enzymes of steroidogenesis, aldosterone synthase deficiency does not lead to adrenal hyperplasia, since cortisol synthesis is not impaired in this syndrome. On fig. 18-4 two last stage biosynthesis of aldosterone, occurring in the glomerular zone of the adrenal cortex.

It is known that the synthesis of corticosterone methyl oxidase (CMO) types 1 and 2 occurs from the same gene CYP11B2, located on chromosome 8 (8q21). Depending on the particular mutation, either the 18-hydroxylase activity of the enzyme or the aldehyde synthase activity is affected. Therefore, 2 forms of aldosterone synthase deficiency are distinguished: deficiency of KMO-1 and KMO-2. These forms of the disease are different

from a friend only hormonal profile. With a deficiency of KMO-1, low concentrations of both aldosterone and 18-hydroxycorticosterone are determined, while with a deficiency of KMO-2, the content of 18-hydroxycorticosterone is significantly increased, and the concentration of aldosterone is low. The differential diagnostic criterion for these conditions is the ratio of 18-hydroxycorticosterone to aldosterone: with KMO-1 deficiency, this indicator is less than 10, and with KMO-1 deficiency, it exceeds 100.

Clinical signs do not depend on the form of the disease.

Rice. 18-4.biosynthesis of aldosterone.

Newborns vomit. The child refuses food, stops gaining weight - dehydration develops. According to laboratory studies, hyperkalemia, sometimes hyponatremia, and high plasma renin activity are noted. In these patients, with age, a positive trend is observed regarding the salt loss syndrome, however, a delay in physical development is noted. In the treatment of patients with aldosterone synthase deficiency, the addition of sodium chloride (table salt) to food and mineralocorticoid preparations (fludrocortisone at a dose of 0.05-0.1 mg / day) are used.

Acquired secondary aldosterone deficiency

Acquired secondary aldosterone deficiency is due to a decrease in renin biosynthesis in the kidneys. As a result of the lack of stimulation of the glomerular zone of the adrenal glands by the renin-angiotensin system, aldosterone synthesis decreases. This disease is characterized by chronic asymptomatic hyperkalemia and some decrease in kidney function. However, some patients may develop muscle weakness and cardiac arrhythmias. Secondary hyporenin hypoaldosteronism is observed in patients with DM, SLE, myeloma, renal amyloidosis, liver cirrhosis, sickle cell anemia, autonomic polyneuropathy, and AIDS.

The cause of the disease is damage to the juxtaglomerular apparatus of the kidneys, which leads to reduced secretion of renin. There are several theories to explain hyporeninemia. For example, long-term hypervolemia leads to irreversible suppression of the function of the juxtaglomerular apparatus. Another cause of hyporeninemia may be insufficient activity of the autonomic nervous system, for example in patients with diabetes. The third possible mechanism may be a violation of the conversion of prorenin to renin due to a deficiency of kallikrein or PgI 2.

Patients with hyporeninic hypoaldosteronism are characterized by a special form of renal tubular acidosis. In the development of acidosis, not only mineralocorticoid deficiency plays a role, but also hyperkalemia, which reduce renal ammoniogenesis, reduce the secretory activity of the distal nephron for H+ ions.

The diagnosis of secondary hyporeninemic hypoaldosteronism should be considered in all patients with chronic hypokalemia. The clinical diagnosis is confirmed by low blood levels of aldosterone in combination with low plasma renin activity. The results of stimulation diagnostic tests that cause activation of the renin-angiotensin-aldosterone system (orthostatic test, test with furosemide) are negative.

Therapy of hyporeninic hypoaldosteronism is aimed at correcting hyperkalemia. In patients with moderate hyperkalemia without ECG changes, electrolyte and ECG monitoring should be performed. Such patients should be advised a potassium-restricted diet and warned against taking drugs that cause hyperkalemia (β-blockers, ACE inhibitors, sodium heparin, potassium-sparing diuretics, cyclooxygenase inhibitors). Therapy with mineralocorticoids is carried out in patients with severe hyperkalemia, without arterial hypertension and congestive heart failure.

Pseudohypoaldosteronism

Pseudohypoaldosteronism is a condition characterized by the clinical picture of salt loss syndrome, but accompanied by high concentrations of aldosterone and renin. The cause of this pathology is considered to be a violation of the mechanism of action of aldosterone. Allocate pseudohypoaldosteronism with an autosomal recessive type of inheritance, the cause of which is the pathology of amiloride-sensitive sodium channels in the distal nephron, which leads to increased excretion of sodium from the body. Mutations in the genes encoding the α- (SCNN1A), β- (SCNN1B) and γ-subunit (SCNN1G) of the amiloride-sensitive sodium channel located on chromosomes 12 (12p13) and 16 (16p13-p12) have been identified.

In autosomal dominant and sporadic forms of the disease, the cause of pseudohypoaldosteronism is the pathology of the mineralocorticoid receptor, the gene of which is located on the short arm of chromosome 4 (4q31.1).

A distinctive feature of the clinical picture of pseudohypoaldosteronism caused by sodium channel pathology is the absence of damage to other mineralocorticoid-sensitive tissues (sweat glands, intestines). Laboratory and diagnostic criteria for this pathology is hyperkalemia in combination with a high content of aldosterone and renin in the blood.

Mineralocorticoids in the treatment of pseudohypoaldosteronism are not effective, since the mechanism of the action of aldosterone itself is disrupted. Treatment of such patients is reduced to compensation of losses of salt and water.

Congenital dysfunction of the adrenal cortex

Congenital dysfunction of the adrenal cortex (adrenogenital syndrome, congenital adrenal hyperplasia) is a group of diseases with an autosomal recessive type of inheritance, which are based on a defect in one of the enzymes or transport proteins,

involved in the biosynthesis of cortisol in the adrenal cortex. A decrease in cortisol biosynthesis by the feedback principle leads to an increase in ACTH secretion and, as a result, to the development of hyperplasia of the adrenal cortex and the accumulation of metabolites that precede the defective stage of steroidogenesis. Enzymatic disorders are based on defects in the genes encoding one or another enzyme of steroid biosynthesis.

Depending on which enzyme of steroidogenesis falls out, there are 5 main forms of this disease. The most severe form is lipoid adrenal hyperplasia due to a defect in the StAR protein. With this form of the disease, the synthesis of all hormones of the adrenal cortex is practically absent, and it was previously believed that this was incompatible with life. The most commonly diagnosed disease is caused by a deficiency of the enzyme 21-hydroxylase. This form accounts for 75% of all cases of the disease. More rarely, a 3-hydroxysteroid dehydrogenase defect, 17a-hydroxylase deficiency, or 11 b -hydroxylases. On fig. 18-5 is a diagram of steroidogenesis. The clinical picture of the disease depends on the location of the steroid synthesis block. It is clear that there will be a deficiency of steroids below the block and, conversely, an excess of steroids that are synthesized before the block.

Deficiency of 21-hydroxylase is one of the most common congenital enzymatic disorders of steroidogenesis. The incidence of classical variants of the disease in various populations ranges from 1:10,000 to 1:18,000 newborns. An extremely high incidence was determined in two isolated populations: among the Eskimos of western Alaska -1:280 and among the inhabitants of La Runyon Island in Indian Ocean- 1:2100. The disease is inherited in an autosomal recessive manner.

Etiology

The defect in 21-hydroxylase is due to numerous mutations in the gene encoding this enzyme - CYP21. The gene is located on the short arm of chromosome 6.

Pathogenesis

21-hydroxylase is a microsomal P450-dependent enzyme involved in the biosynthesis of cortisol and mineralocorticoids, transforming 17a-hydroxyprogesterone into 11-deoxycortisol and progesterone into deoxycorticosterone. Deficiency of 21-hydroxylase leads to a decrease in the production of cortisol, which causes an increase in the secretion of ACTH and leads to hyperplasia of the adrenal cortex. The adrenal glands actively secrete steroids that precede

Rice. 18-5.Diagram of steroidogenesis.

enzymatic block: 17a-hydroxyprogesterone and androgens, the biosynthesis of which does not depend on 21-hydroxylase.

Mineralocorticoid deficiency of varying severity is diagnosed in 75% of children with 21-hydroxylase deficiency. A decrease in the concentrations of deoxycorticosterone and aldosterone leads to a decrease in sodium reabsorption in the kidneys. In this regard, the concentration of sodium in the blood serum falls and the renal reabsorption of potassium increases. As a result of these disorders, hyponatremia, hyperkalemia, acidosis, and dehydration develop. In response to a decrease in the production of mineralocorticoids, plasma renin activity increases.

Clinical picturePrenatal virilization

The classic variant of 21-hydroxylase deficiency leads to severe hyperandrogenism, which is still forming intramuscularly.

timidly. It is assumed that active virilization of the fetus begins from the 20-25th week of gestation, when the effect of ACTH on the embryonic adrenal gland is formed and cortisol begins to be synthesized. Intrauterine hyperandrogenism leads to active virilization of the external genitalia, which is most dramatic in girls. By the time of birth, the external genital organs of the girl have a bisexual structure: the clitoris is hypertrophied, fusion of the scrotolabial (scrotal) suture of varying severity is noted. In some cases, intrauterine androgenization is so pronounced that the external genitalia practically correspond to the male, and the girl is mistakenly registered and raised as a boy (Fig. 18-6 on the insert).

There are 5 degrees of virilization of the external genital organs according to Prader. The reference point is considered to be the normal external genitalia of the girl (there is no virilization). The maximum degree of virilization corresponds to the normal structure of the external genital organs of the boy.

I degree of virilization - clitoral hypertrophy and normal entrance

into the vagina.

II degree of virilization - clitoral hypertrophy and partial fusion of the labia majora (high posterior commissure).

III degree of virilization - the clitoris is hypertrophied and its head is formed, the fusion of the labia forms the urogenital sinus (a single urogenital opening at the base of the clitoris).

IV-V degree of virilization - a hypertrophied clitoris resembles a normal penis, however, its curvature (fixation to the perineum) is observed, the urogenital sinus opens on the trunk or glans penis (pineal urethra). The severity of virilization in children with 21-hydroxylase deficiency varies significantly and is primarily due to the nature of the gene mutation CYP21. In boys, at birth, the external genitalia correspond to the sex of the child, there may be a slight increase in the penis.

Postnatal virilization

After birth, the symptoms of androgenization increase in children of both sexes. In girls, the size of the clitoris increases, its tension is noted. In boys, the size of the penis increases, erections occur. It should be noted that the symptoms of androgenization may not appear in the first 1.5 years of a child's life. By the age of 1.5-2 years, sexual hair is formed in children of both sexes, acne vulgaris, voice coarsens, muscles hypertrophy. In the first years of life, the linear growth of children is accelerated, but the degree of bone differentiation is ahead of growth. Growth zones close by 9-10 years.

The degree of pre- and postnatal androgenization in patients with 21-hydroxylase deficiency can have significant individual variations even in sick siblings in the same family with the same genetic defect. This may be due to individual features androgen precursor metabolism and differences in androgen receptor activity in a particular patient.

Salt-wasting syndrome (salt-wasting syndrome)

Complete loss of 21-hydroxylase activity seen in 75% of deficient children R450s21, leads to a decrease in the biosynthesis of aldosterone. Aldosterone is essential for maintaining normal sodium homeostasis, and its deficiency leads to sodium loss through the kidneys, intestines, and sweat glands. The presence of a pronounced salt-losing component associated with mineralocorticoid deficiency poses a serious threat to the life of a child from the first days of life. 3-4 days after birth, hyperkalemia increases, and a few days later hyponatremia and hypernatriuria develop. Loss of salt leads to severe dehydration and weight loss. Dehydration is aggravated by frequent massive vomiting caused by hyperkalemia. In the absence of therapy, the death of the child may occur as a result of collapse and cardiogenic shock.

reproductive function at classical form 21-hydroxylase deficiency

Puberty in untreated children of both sexes comes late. In girls, even with an extreme degree of virilization, mammary glands can develop (no more than grade II according to Tanner) and menstrual flow appears. A regular menstrual cycle is possible only against the background of adequate glucocorticoid therapy. The ovaries are reduced, with signs of polycystic. The causes of menstrual dysfunction are primarily due to an excessive concentration of adrenal androgens, which suppress the cyclic secretion of gonadotropins and directly inhibit the development of the follicle, causing its premature atresia.

In boys, the function of the gonads is more preserved than in girls. In adult untreated patients, oligospermia is possible.

In children of both sexes, with late treatment with glucocorticoid preparations, premature activation of the hypothalamic-pituitary-gonadal system is possible - true precocious sexual development. As a rule, this phenomenon is observed in children whose bone age reaches puberty at the beginning of treatment: 11.5-12 years in girls and 13.5-14 years in boys (development of sesamoid bone). In girls, the mammary glands begin to increase, in boys, the volume of the testicles increases. The reason for the early activation of true puberty in these children is not entirely clear. Perhaps an excess of

lovy steroids changes the sensitivity of the hypothalamic centers and contributes to their "maturation". A rapid decrease in excess secretion of adrenal androgens in the appointment of glucorticoid therapy contributes to the activation of the secretion of gonadotropin-releasing hormone by the hypothalamus, which stimulates gonadotropic and gonadal functions. Early true puberty in children with 21-hydroxylase deficiency worsens the growth prognosis and requires the addition of antigonadotropic therapy.

Non-classical form of 21-hydroxylase deficiency

The prevalence of non-classical variants of 21-hydroxylase deficiency in the general population is very high and amounts to 0.3%. In some ethnic groups, the non-classical form of the disease is observed even more often: 1.6% in Yugoslavia, 1.9% in Spain, 3.7% in Western European Jews (Ashkenazi). In non-classical forms of the disease, the decrease in the activity of the 21-hydroxylase enzyme varies within a fairly wide range and can be 20-60% of normal values. In this regard, the clinical signs of hyperandrogenism can be extremely variable. For children with a non-classical form of the disease, symptoms of postnatal virilization are not typical. At birth, the external genitalia of girls are formed according to female type. Rarely, there may be slight enlargement of the clitoris and a high posterior perineal commissure that forms a funnel-shaped vaginal opening. In children of both sexes, the most common symptom of the non-classical form of the disease is the early appearance of pubic and axillary hair growth (adrenarche). A slight increase in growth rate and bone maturation is also noted, but the final height of these children is in line with the genetically expected.

In pubertal girls and adult women, mild 21-hydroxylase deficiency manifests as hirsutism. Possible violation of menstrual function and the formation of polycystic ovaries, which leads to infertility. However, in 50% of women with a non-classical form of 21-hydroxylase deficiency, reproductive function is not impaired.

Determination of the level of 17a-hydroxyprogesterone is indicated for all newborns with an abnormal structure of the external genital organs in the absence of palpable testicles.

In parallel, karyotyping is carried out. Determination of the 46XX karyotype in a child with a bisexual structure of the external genital organs with a 95% probability indicates the presence of 21-hydroxylase deficiency. A high concentration of 17a-hydroxyprogesterone finally confirms the diagnosis.

In preterm infants and children who have suffered a severe birth injury or were born with a lack of body weight at normal gestation periods, the content of 17a-hydroxyprogesterone may be increased in the absence of 21-hydroxylase deficiency. In these cases, it is recommended to repeat the study (2-3-4 times with an interval of 5-7 days). A decrease in the content of 17a-hydroxyprogesterone in dynamics makes it possible to exclude 21-hydroxylase deficiency. The development of a salt-wasting crisis with 21-hydroxylase deficiency is rarely observed in newborns and children in the first seven days of life. However, until hormonal data are available to confirm or rule out 21-hydroxylase deficiency, all children should be monitored for electrolyte levels in the blood.

An increase in the concentration of potassium and a decrease in the content of sodium in the blood serum of a child with a bisexual structure of the external genital organs, accompanied by clinical signs of a salt-wasting syndrome, should be considered as a manifestation of 21-hydroxylase deficiency and therapy should be prescribed immediately, without waiting for the results of a hormonal analysis.

The presence of 21-hydroxylase deficiency in newborn boys can only be suspected in the presence of a salt-wasting syndrome. All newborn boys with clinical signs of hyperkalemia, hyponatremia and dehydration should have 17a-hydroxyprogesterone levels determined.

Laboratory and instrumental research

The main sign of 21-hydroxylase deficiency is an increase in the level of 17a-hydroxyprogesterone in the blood serum (10 times or more) due to a block in the synthesis of cortisol. It is necessary to study the level of potassium and sodium in the blood serum to assess the degree of mineralocorticoid deficiency.

In all children with a bisexual structure of the external genitalia, it is necessary to examine the karyotype.

Molecular diagnostics based on the identification of mutations in a gene CYP21, allows you to accurately confirm or exclude the presence of 21-hydroxylase deficiency. For prenatal diagnosis, the molecular genetic method is considered the only reliable way to detect the disease and its form in the fetus.

Diagnosis and differential diagnosis

Neonatal screening for 21-hydroxylase deficiency

Diagnosis of 21-hydroxylase deficiency is based on clinical signs of the disease. In the first weeks of a child's life, the disease can be suspected by the presence of virilization of the external genitalia in girls and the development of salt loss syndrome in children of both sexes. The viril form of the disease in boys is diagnosed only by 4-5 years of age with the development of symptoms of precocious sexual development. Bone age is already significantly ahead of chronological age. Such a clinical approach to the diagnosis of 21-hydroxylase deficiency leads to a large number of errors. Up to 30% of girls with severe signs of virilization of the external genitalia are mistakenly registered as having a male sex. Up to 35% of boys with a salt-wasting form of the disease die in the first weeks of life, since the disease is not recognized in time. Neonatal screening for the detection of 21-hydroxylase deficiency makes it possible to avoid diagnostic errors. Screening is based on the determination of the content of 17a-hydroxyprogesterone in a dry blood spot on filter paper. By 1991, a neonatal screening program had been introduced in 29 countries around the world. The implementation of this program made it possible to determine the real frequency of deficiency of 21-hydroxylase and its forms in various populations.

Various forms of congenital dysfunction of the adrenal cortex are presented in Table. 18-5.

Table 18-5.Differential diagnosis of various forms of congenital dysfunction of the adrenal cortex

Salt loss syndrome often has to be differentiated from pyloric stenosis, pylorospasm, and acute illness accompanied by vomiting. The incorrect structure of the external genital organs requires the exclusion of true and false hermaphroditism. Intrauterine virilization syndrome in girls can sometimes be caused by the intake of certain drugs by women during pregnancy. Hormonal and molecular genetic diagnostics allows diagnosing and clarifying the form of adrenogenital syndrome.

Treatment

Treatment of congenital disorders of adrenal steroidogenesis

General goals for the treatment of all forms of congenital disorders of adrenal steroidogenesis:

Replace the deficiency of steroids, the secretion of which is reduced as a result of an enzymatic defect;

Reduce the concentration of steroids, the secretion of which is increased as a result of an enzymatic defect;

Suppress excessive secretion of ACTH, using the least effective

effective doses of glucocorticoids;

Optimize the growth of patients;

Prevent virilization of the external genitalia;

Ensure normal puberty and fertility.

Therapy for 21-hydroxylase deficiency

The main method of therapy for 21-hydroxylase deficiency is the use of glucocorticoids, which suppress the hypersecretion of ACTH and normalize the production of androgens by the adrenal glands. Various medications with glucocorticoid activity are used: prednisolone, cortisone, dexamethasone. Prolonged synthetic glucocorticoid drugs (prednisolone, dexamethasone) have a negative effect on growth processes. Their prolonged effect can quickly lead to overdose symptoms. For children with open growth zones, especially younger ones, the most optimal drugs should be considered hydrocortisone tablets (for example, Cortef). The initial daily dose of hydrocortisone required to suppress ACTH in children of the first year of life can reach 20 mg / m 2. However, prolonged use of these doses in a child should be avoided. The use of hydrocortisone at a dose of 25 mg / m 2 during the year leads to a pronounced delay or cessation of growth! In the case of a prolonged overdose of glucocorticoids at a younger age, growth retardation cannot be eliminated, even against the background of a decrease in the dose of drugs. On average, the daily dose of hydrocortisone should be 10-15 mg/m 2 . The drug is prescribed 3 times a day in

equal doses (at 7.00, 15.00, 22.00). All children with a salt-wasting form of 21-hydroxylase deficiency require additional administration of mineralocorticoid preparations.

Indications for prescribing mineralocorticoid therapy include:

Development of clinical symptoms of a salt-wasting crisis;

High serum potassium levels in the absence of

clinical symptoms of salt loss;

High renin activity of blood plasma at normal con-

concentration of potassium and the absence of clinical symptoms of salt loss.

The dose of fludrocortisone is 0.05-0.3 mg/day. Such therapy makes it possible to compensate for the lack of mineralocorticoids, to achieve more rapid suppression of excess ACTH secretion with the use of lower doses of glucocorticoids. In the presence of mineralocorticoid deficiency, the need for mineralocorticoids is maximum in children of the first year of life and is 0.1-0.3 mg/day. daily dose prescribed in three doses (at 7.00, 15.00, 23.00). Additionally, an excess amount of table salt is introduced into the diet - up to 2 g / day.

In the future, the need to continue therapy with mineralocorticoids is based on indicators of plasma renin activity. In older children, the dose of mineralocorticoids is reduced to 0.05-0.15 mg / day. The daily dose is prescribed in two doses (at 8.00 and 18.00).

Monitoring the adequacy of therapy

Monitoring the adequacy of therapy for 21-hydroxylase deficiency is based on indicators of physical development and hormonal study data. Children of the first 2 years of life should be examined by a pediatric endocrinologist every 3 months. Children older than 2 years should be examined every 6-12 months. On examination, body weight and height are carefully recorded. Determine concentrations 17 b -hydroxyprogesterone and electrolytes. Conduct a study of renin activity of blood plasma. In older children, bone age is examined annually, testosterone levels are determined.

Adequate glucocorticoid therapy ensures normal growth and bone maturation.

Therapy for urgent conditions

Parents of patients with 21-hydroxylase deficiency should be informed about changes in drug therapy in emergency and stressful situations. This information must be issued in the form of written recommendations in addition to official medical records. Older children and adolescents should

have a card with you, in which you need to make recommendations about therapy in emergency situations.

In intercurrent diseases, all patients with high (>38.5 °C) body temperature, vomiting, injuries, and surgical interventions require additional administration of hydrocortisone. With stressful physical activity (participation in competitions), there may be a need to increase the dose of glucocorticoids. Emotional and mental stress (exams) do not require additional administration of drugs.

During a period of stress, the dose of glucocorticoids should be increased by 2-3 times. In cases where oral administration of drugs is not possible, parenteral administration of hydrocortisone should be provided.

In severe intercurrent diseases and surgical interventions, intramuscular administration of hydrocortisone at a dose of 3-5 mg/kg per injection every 4-6 hours and an additional intravenous drip of sodium chloride solution in an amount of 150 ml/kg per day should be used. In this case, 25% of the indicated volume of fluid must be administered in the first 2 hours of therapy.

Surgical strategy for the correction of the external genitalia in girls

Surgical correction of the external genital organs is performed for girls with symptoms of intrauterine virilization. Target surgical correction- to achieve compliance of the external genital organs with the chosen (female) sex, to eliminate possible anatomical obstacles that impede the outflow of urine, to create conditions for normal reproductive function.

Prenatal diagnosis and treatment of 21-hydroxylase deficiency

Classical and non-classical 21-hydroxylase deficiency is considered one of the most common diseases with autosomal recessive inheritance. Developing a content research method 17 a -hydroxyprogesterone in a drop of blood applied to filter paper has allowed mass screening of newborns in various populations. As a result of these large-scale studies, it was found that the average incidence in the world is 1:13,500. At the same time, in some populations this frequency is much higher.

Prevention

As with all autosomal recessive hereditary diseases, a decrease in the frequency of consanguineous marriages is accompanied by a decrease in the incidence.

Forecast

Screening of newborns and adequate therapy from the first days of life significantly improve the prognosis of the disease and social adaptation children. Prenatal diagnosis and treatment make it possible to avoid virilization of the external genitalia in girls with 21-hydroxylase deficiency by the time of birth.

Diabetes

DM is a group of metabolic diseases of various etiologies, characterized by chronic hyperglycemia resulting from impaired secretion or action of insulin, or both factors simultaneously (WHO, 1999).

The WHO research group, taking into account new data, revised the classification of diabetes. This classification included clinical forms of the disease and statistical risk classes.

ETIOLOGICAL CLASSIFICATION OF DIABETES MELLITUS (WHO, 1999)

Type 1 diabetes (destruction of β-cells, usually leading to absolute insulin deficiency):

autoimmune;

Idiopathic.

Type 2 diabetes (with predominant insulin resistance and relative insulin deficiency or a predominant defect in insulin secretion with or without insulin resistance).

Gestational SD.

Other specific types of SD:

Genetic defects in β-cell function;

Genetic defects in the action of insulin;

Diseases of the exocrine part of the pancreas;

Endocrinopathy;

Diabetes induced by drugs or other chemicals;

Diabetes induced by infections;

Unusual forms of immune-mediated diabetes;

Other genetic syndromes sometimes associated with SD.

Type 1 and type 2 diabetes are the most common forms of diabetes. They differ in clinical, epidemiological and immunological characteristics, the nature of insulin secretion, association with genetic markers.

Type 1 diabetes is most commonly seen in children and individuals young age although the disease can manifest at any age. Autoimmune DM is characterized by the destruction of β-cells, the presence of autoantibodies, absolute insulin deficiency, complete insulin dependence, severe course with a tendency to ketoacidosis, association with the major histocompatibility complex genes HLA. Cases of idiopathic diabetes are usually recorded in non-Caucasian individuals with destruction of β-cells, a tendency to ketosis, but an unknown pathogenesis.

Type 2 diabetes among adults is dominant. It is rarely seen in childhood. Type 2 diabetes in childhood is often asymptomatic or with minimal clinical symptoms. At the same time, with infectious diseases or severe stress, ketoacidosis can sometimes develop. In the development of the disease in children, the main importance is attached to the genetic factor. Monozygotic twins in 100% of cases are concordant (similar) in type 2 diabetes. Parents are also diagnosed with type 2 diabetes in most cases, especially when examining a glucose tolerance test. Behavioral habits such as overeating and reduced physical activity are of great importance in the initiation of the disease. Intrauterine growth retardation with underweight, as well as malnutrition in the early postnatal period, can also contribute to the development of type 2 diabetes in childhood due to excessive feeding of the child, leading to the formation of obesity, hyperinsulinism, and insulin resistance.

For a long time it was believed that only one form is characteristic of childhood - type 1 diabetes. However, studies of the last decade have convincingly shown that, along with the dominant type 1 DM, more rare combinations of DM with genetic syndromes, type 2 DM, which is predominant in adults, and the MODY type, which was considered specific only for youth, are also diagnosed in childhood. age. Currently, the incidence of type 1 diabetes in children in Russia is 9.24 per 100,000 children.

ETIOLOGY

The development of type 1 diabetes is based on a genetic predisposition. This is evidenced by familial cases of the disease, as well as a high frequency of repeated cases of the disease among monozygotic twins.

The family concentration of type 1 diabetes (or the frequency of recurrent cases of the disease in the families of patients) is determined by the following factors:

The frequency of DM in the population;

The number of sick and healthy relatives, the degree of their kind

stva;

The age of onset of DM in the proband, in some cases -

gender of the proband;

The age of the examined relatives, in some cases - their

floor.

In table. Figures 18-6 show empirically derived risk rates for developing type 1 diabetes in various relative groups for populations with a high incidence rate (0.4%).

Table 18-6.Empirical risk of developing the disease in relatives of patients with type 1 diabetes (Eisenbart, 1994)

As shown by numerous studies in recent years, type 1 DM is an autoimmune disease in genetically predisposed individuals, in which long-term chronic lymphocytic insulitis leads to the destruction of β-cells, followed by the development of insulin deficiency.

An initiating or provoking factor is required to initiate an autoimmune process. external environment(trigger). On present stage there is no single and undoubted view on the nature of such a factor. Currently, the most probable factors involved in triggering the destruction of islet cells are identified.

Viruses: Coxsackie B, rubella, mumps, enteroviruses, rotaviruses, cytomegalovirus, Epstein-Barr, ECHO, etc.

Nutritional factors: cow's milk and cow's milk-based mixed feeding, duration of breastfeeding, nitrates.

Exposure to toxins.

PATHOGENESIS

Mechanisms of damage to β-cells by viruses:

Direct destruction (lysis) of β-cells as a result of infection

a virus;

The mechanism of molecular mimicry, in which an immune response directed to viral Ag, similar to the β-cell's own Ag, damages the islet cell itself;

Violation of the function and metabolism of β-cells, resulting in

abnormal antigens are expressed on its surface, which leads to the launch of an autoimmune reaction;

Interaction of the virus with the immune system.

The stages of development of type 1 diabetes are shown in Fig. 1. 18-7.

Autoantibodies to various structures of β-cells are considered as immunological markers of β-cell destruction.

Insulin is the main hormone that regulates metabolism, the end result of which is the provision of energy and plastic processes in the body. The target organs of insulin action include the liver, muscle and adipose tissue. Insulin can have anabolic and anti-catabolic effects. The anabolic effect of insulin is realized through the stimulation of the synthesis of glycogen and fatty acids in the liver, triglycerides in adipose tissue, protein and glycogen in muscle tissue. The anti-catabolic effect of insulin is to suppress the processes of glycogenolysis, gluconeogenesis (the formation of glucose from fats and proteins) and ketonogenesis (the formation ketone bodies). In the body, there are also insulin-independent tissues (kidneys, brain, Schwann cells of peripheral nerves, lens tissue, arteries, retina), in which insulin is not required to transfer glucose into the cell.

The mechanism of action of insulin is to activate the transport of glucose across the cell membrane, as well as the stimulation of various enzymes involved in different stages in exchange processes. Insulin acts by binding to specific receptors on cytoplasmic membranes.

All clinical symptoms are due to a lack of production and action of insulin. In children, this is mainly due to the death of pancreatic β-cells, i.e. there is an absolute deficiency of insulin.

CLINICAL PICTURE

Diabetes can develop in a child at any age. During the first months of life, the disease is rarely observed. The risk increases after 9 months, increases significantly after 5 years and at puberty, and decreases slightly in adults.

Rice. 18-7.Stages of development of insulin-dependent diabetes mellitus (Singer A., ​​Stendl E.): Stage I - a genetic predisposition realized in less than half of genetically identical twins and in 2-5% of siblings; stage II - a hypothetical starting point that causes the development of stage III; Stage III - an active autoimmune process (initially, individuals, even with immune disorders, have normal insulin secretion); Stage IV - with severe immune disorders, a decrease in insulin secretion in response to the administration of glucose is noted, while the level of glycemia remains normal; Stage V - a clinical manifestation that develops after the death of 80-90% of β-cells, while residual insulin secretion is still preserved; Stage VI - complete destruction of β-cells.

The vast majority of patients develop type 1 diabetes in childhood, which is characterized by severe insulin deficiency and is always insulin dependent. Clinical signs of DM largely depend on the age of the child and the degree of decompensation of metabolic processes at the time of his examination. Type 1 diabetes in childhood is characterized by an acute onset with a rapid increase in symptoms up to the onset of ketoacidosis, and in the absence of timely diagnosis, ketoacidotic coma may develop. In most children, the time from the onset of the first symptoms of the disease to the onset of a coma ranges from 3-4 weeks to 2-3 months.

In middle-aged and older children, it is not difficult to suspect the presence of DM. The main symptoms of SD include:

Polyuria (increased urination);

Polydipsia (thirst);

dry mouth;

Polyphagia (increased appetite);

Decrease in body weight;

The smell of acetone from the mouth.

Polyuria- the first symptom of glucosuria occurs when hyperglycemia exceeds the renal threshold for glucose (mean 9 mmol/l). Polyuria develops as a result of osmotic diuresis due to a high concentration of glucose in the urine. Urine is usually colorless, has a high specific gravity due to the release of sugar. In the daytime, this symptom, especially in children of school age, does not attract the attention of either children or adults. At the same time, nocturnal polyuria and urinary incontinence, which often accompanies it, are usually more noticeable. Enuresis is characteristic of severe polyuria and is often the first symptom of diabetes to be noticed. Often the attention of parents is attracted by the appearance of sticky urine. Polyuria is a compensatory process, as it helps to reduce hyperglycemia and blood hyperosmolarity.

Polydipsiaoccurs against the background of polyuria due to dehydration of the body and irritation of the thirst center of the brain due to blood hyperosmolarity. As well as polyuria, thirst is more noticeable at night, and also in the morning, before breakfast. Dry mouth causes the child to wake up several times during the night and drink water.

Polyphagia(constant feeling of hunger) in combination with weight loss is one of the characteristic signs of diabetes. They develop as a result of energy starvation of the cells of the body due to a violation of the utilization of glucose and its loss in the urine, on the one hand, and an increase in the processes of lipolysis and proteolysis under conditions

insulin deficiency on the other. drastic loss body weight is also due to dehydration. Parents do not always characterize polyphagia as a pathological symptom and do not record it among complaints, and often even regard it as a positive phenomenon in the child's condition. To a greater extent, parents are worried about the loss of body weight of the child. The combination of polyphagia with weight loss usually prompts a visit to the doctor. However, often the examination of the child goes in the wrong direction (most often along the path of exclusion). helminthic invasion, gastrointestinal disease, chronic infection etc.), and thus the patient is left without medical care. In the future, the child develops general and muscle weakness, which is explained not only by energy starvation of the cells, but also by increasing electrolyte disturbances.

Increased lipolysis in adipose tissue leads to an increase in the concentration of free fatty acids in the blood, which enhance ketogenesis due to the reduced liposynthetic function of the liver under conditions of insulin deficiency. The accumulation of ketone bodies leads to the development of diabetic ketoacidosis. In patients, the smell of acetone from the mouth appears, polyphagia is replaced by reduced appetite, weakness increases, shortness of breath occurs, first during exercise, and then at rest. Subsequently, anorexia, nausea, vomiting, drowsiness join these symptoms. These are formidable harbingers of the development of a coma. Often in the debut of diabetes in children, pseudo-abdominal syndrome can be observed. Abdominal pain, nausea, vomiting that occurs with rapidly developing ketoacidosis are regarded as symptoms surgical pathology. Often such children are mistakenly subjected to laparotomy in connection with a suspected acute abdomen.

Skin changes often registered in the debut of SD. Dryness of the skin and mucous membranes due to dehydration of the body becomes an almost constant symptom of the disease. Dry seborrhea may occur on the scalp, and peeling may occur on the palms and soles. The mucous membrane of the oral cavity is usually bright red, dry, in the corners of the mouth - irritation, seizures. Thrush, stomatitis can develop on the mucous membrane of the oral cavity. Diabetic blush, which often affects the forehead and chin, except for the cheeks, is associated with paresis of skin capillaries in hyperglycemia and ketosis. Sometimes attention is drawn to icteric coloration of the skin of the palms, soles, nasolabial triangle (xanthosis). It is caused by the deposition of carotene in the stratum corneum due to a violation of its conversion in the liver to vitamin A. Skin turgor, as a rule,

reduced, especially with severe dehydration. Most often, there is a lack of body weight, sometimes up to cachexia.

Cardiovascular disorders in the debut of the disease is observed only with severe decompensation. These include tachycardia, muffled heart sounds, the presence of functional noise. An ECG study records metabolic changes.

Hepatomegalyin children is noted quite often. Its severity depends on the degree of metabolic disturbance. Enlargement of the liver in diabetes is usually associated with fatty infiltration due to insulin deficiency. The appointment of insulin and compensation of carbohydrate metabolism lead to the normalization of the size of the liver.

Menstrual irregularities may accompany the onset of DM in puberty in girls. There may be complaints of itching in the vulva and other parts of the body.

The course of the disease

The course of the disease depends on the age of the child. In many children of the first 5 years of life, the course of the disease is characterized by extreme instability, a tendency to frequent hypoglycemic states, the ease of developing ketosis, and increased sensitivity to insulin. Avoiding hypoglycemia in young children is difficult due to fluctuating appetite and variable exercise. The labile course of DM is noted in children both in the prepubertal and pubertal periods. It is due to the instability of neurohumoral regulation, the intensity of metabolic processes due to intensive growth and development. Insulin resistance is pronounced at all stages of puberty. Particular attention should be paid to the emotional factor that affects the course of the disease in adolescents.

Complications

diabetic retinopathy

Diabetic retinopathy is a classic example vascular complications SD. It occupies one of the first places among the causes leading to decreased vision and blindness in young people. Disability due to visual impairment is observed in more than 10% of patients with DM. Blindness occurs 25 times more often than in the general population.

Diabetic retinopathy is a specific lesion of the retina and retinal vessels, characterized by the development of exudative foci, retinal and preretinal hemorrhages, the growth of newly formed vessels, as well as the development of traction retinal detachment, rubeous glaucoma.

diabetic nephropathy

Diabetic nephropathy is the main cause of poor prognosis in diabetic patients. It is known that one third of all patients with type 1 diabetes die from terminal renal failure already 15-20 years after the onset of the disease. The most unfavorable outcome is observed in persons who fell ill in childhood.

Diabetic neuropathy

Diabetic polyneuropathy is characterized by the occurrence of pain in the extremities, a decrease in the threshold of temperature and pain sensitivity. The development of autonomic polyneuropathy, manifested by dysfunction of the esophagus, gastropathy, diabetic diarrhea, and constipation, is characteristic.

The risk of developing vascular complications depends on the degree of compensation of the disease. With good compensation, a normal life in terms of duration and quality is possible. The worse the compensation, the faster and more severe diabetic complications develop, life expectancy is reduced by 15-20 years, and early disability occurs.

Diabetic cataract, hepatosis and diabetic hiropathy (limitation of joint mobility) is also referred to as a typical complication of DM.

If diabetes occurs at an early age and poor compensation of the disease, a delay in physical and sexual development is observed. The extreme severity of these symptoms (dwarfism, lack of secondary sexual characteristics in adolescents and hepatomegaly) is called Mauriac's syndrome (Fig. 18-8 on the insert).

LABORATORY AND INSTRUMENTAL STUDIES

The diagnosis is confirmed by the presence of hyperglycemia, glucosuria, in some patients - ketosis or ketoacidosis. Normally, the content of glucose in the blood plasma on an empty stomach is 3.3-5.5 mmol / l.

Glucosuriaserves as an important diagnostic criterion for DM. Normally, a healthy person does not have glucose in the urine. Glycosuria occurs when the concentration of glucose in the blood plasma exceeds 8.88 mmol / l. Diagnosis of diabetes in the detection of glucosuria can be considered reliable only after determining hyperglycemia.

Ketonuria or acetonuria. The presence of ketone bodies (derivatives of lipid metabolism) in the urine indicates a severe decompensation of diabetes associated with a lack of insulin. However, in children, ketonuria can be noted in infectious diseases that occur with high temperature body, during fasting, especially in young children.

Determination of the content of glycosylated Hb (HbA 1c) is considered one of the modern methods for diagnosing carbohydrate disorders.

exchange. In addition, this method is also used to assess the degree of compensation of carbohydrate metabolism in patients with DM who are on treatment.

The content of HbA 1c depends on the concentration of glucose in the blood plasma and serves as an integral indicator of the state of carbohydrate metabolism over the past 3 months, given that the "life" of an erythrocyte is 120 days. The content of HbA 1c is 4-6% of total Hb in the blood of healthy individuals. A high level of glycemia in DM contributes to an increase in the processes of non-enzymatic glycosylation of Hb proteins, therefore, in patients with DM, its content is 2-3 times higher than the norm. For the diagnosis of diabetes in children, this indicator is of great importance.

Autoantibodies to Ag β -cells(ICA, GADA, IAA, IAA) serve as immunological markers of insulitis occurring in the pancreas. Their determination is used for early preclinical diagnosis of type 1 diabetes in high genetic risk groups or for differential diagnosis between type 1 and type 2 diabetes. If a child has classic symptoms of DM, there is no need to determine autoantibodies to β-cell Ag.

Definition of content C-peptide in blood serum makes it possible to assess the functional state of β-cells in individuals with a high risk of developing diabetes and, in addition, helps in the differential diagnosis of type 1 and type 2 diabetes. The basal concentration of C-peptide in healthy individuals is 0.28-1.32 pg/ml. In type 1 DM, its content is reduced or not detected. After stimulation with glucose, glucagon, or sustakal (a nutrient mixture with a high content of corn starch and sucrose), the concentration of C-peptide in patients with type 1 diabetes does not increase, and in healthy individuals it increases significantly. In the presence of classical symptoms of type 1 diabetes at the onset of the disease in children, the determination of the content of C-peptide in the blood serum is of no practical importance.

DIAGNOSIS AND DIFFERENTIAL DIAGNOSISDiagnosis of diabetes is made on the basis of the classic symptoms of the disease. Differential diagnosis is carried out with renal diabetes(glucosuria without an increase in plasma glucose concentration), diabetes insipidus (polyuria with low specific gravity of urine and thirst in the absence of glucosuria and hyperglycemia) and acetone vomiting syndrome (ketonuria, acidosis, acetone breath odor in the absence of hyperglycemia).

Until now, the problem of differential diagnosis of DM during its debut remains relevant. In 88% of children, diabetes is diagnosed in a state of ketoacidosis.

TREATMENT

Type 1 DM is a disease based on absolute insulin deficiency caused by autoimmune destruction of insulin-producing cells of the pancreas; therefore, insulin administration is considered the only pathogenetic method of its treatment today. In addition, important points in the treatment of type 1 diabetes include diet, proper lifestyle, sufficient physical activity and self-control.

Treatment goals for children and adolescents with type 1 diabetes:

Achieving the level of carbohydrate metabolism as close to normal as possible;

Normal physical and somatic development of the child;

Normal psychosocial state and adaptation of the child;

Development of independence and motivation for self-control;

Prevention of specific complications of diabetes. Compensation criteria for SD:

Lack of thirst, polyuria, weight loss;

Fasting glycemia 4-7.6 mmol/l;

Absence of glucosuria;

Postprandial glycemia less than 11 mmol/l;

The concentration of glucose at night is not less than 3.6 mmol / l;

Absence of severe hypoglycemia (allow the presence of individual mild hypoglycemia);

Patients with diabetes need to limit the intake of carbohydrates and fats, while taking into account individual physiological needs for nutrients and energy. Recommend the ratio of proteins, fats and carbohydrates 1:0.8:3-3.5.

Currently, children in Russia are prescribed only human genetically engineered insulin preparations and their analogues. Pharmacokinetic characteristics of these drugs are presented in table. 18-7.

Table 18-7.Pharmacokinetic characteristics of various insulin preparations

In addition, mixed preparations of insulin are currently being produced, which include insulin of medium duration and short action in various ratios - from 90:10 to 50:50. These drugs are more convenient because their use reduces the number of injections performed using syringe pens.

Immediately after the diagnosis of diabetes in children is established, insulin therapy should be started. Insulin therapy is started with a fractional injection of a short-acting insulin preparation 4-6 times a day. The dose is selected individually depending on the age of the child and the degree of hyperglycemia. On average, the dose is 0.5-0.8 U / kg / day, and in the future it must be adjusted depending on the content of glucose in the blood plasma. A repeated study of the concentration of glucose in the blood plasma is carried out every 3-6 hours.

The intensified (or basal-bolus) regimen of insulin therapy is currently the most widely used. It consists in the fact that before each main meal, a short-acting insulin preparation is administered, and a prolonged-acting insulin preparation is administered 1-2 times a day, most often in the evening and morning hours. At the same time, using a long-acting insulin preparation, they try to imitate basal secretion, and

when using a short-acting insulin preparation - postalimentary secretion.

Currently, the use of an insulin pump is considered the "gold standard" of insulin therapy. The insulin pump is a modern technology that allows you to effectively compensate for carbohydrate metabolism. The pump is capable of continuously injecting insulin, simulating basal hormone secretion by β-cells, and after a meal, injecting insulin in a bolus mode, simulating postalimentary secretion.

Complications of insulin therapy

hypoglycemia - a condition caused by low levels of glucose in the blood plasma and is one of the most frequent complications insulin therapy. According to various authors, among patients with diabetes, pronounced and asymptomatic hypoglycemia is observed in 25-58% of cases, and in 3-4% of cases, hypoglycemic coma becomes the cause of death in patients with diabetes.

Symptoms of hypoglycemia include decreased intellectual activity, self-doubt, lethargy, lethargy, poor coordination of movements, headache, hunger, weakness, excessive sweating, drowsiness, parasthesia, dizziness, diplopia, "flies" in the eyes, irritability, nightmares, inappropriate behavior, workload, hemiplegia, paresis, impaired consciousness, and as an extreme manifestation of coma.

self control

The accumulated clinical experience shows that neither the use of the best insulin preparations, nor the most selected dose and regimen of insulin administration can solve the problem of compensating for diabetes in childhood and adolescence without self-monitoring of the disease at home.

Self-control in diabetes is considered one of the most important components of treatment. For competent control of diabetes, patients must have a good understanding of all aspects of their disease. Carrying out self-monitoring means not only the ability to determine the content of glucose in blood plasma, but also to correctly adjust the dose of insulin depending on the level of glycemia, changes in nutrition, physical activity and conditions of a diverse range of life situations. To do this, they train patients and their parents in specially created schools of self-control.

EMERGENCIES

Acute emergencies in DM include diabetic ketoacidosis and ketoacidotic coma, as well as hypoglycemia and hypoglycemic coma. Hyperosmolar non-ketoacidotic coma and lactic acidosis in childhood are extremely rare, although

the state of hyperosmolarity is of great importance in the development of ketoacidotic coma.

Diabetic ketoacidosis and ketoacidotic coma

Diabetic ketoacidosis is a severe metabolic decompensation of diabetes. With the manifestation of diabetes, diabetic ketoacidosis develops in 80% of cases when, for one reason or another, the diagnosis of the disease is delayed, or when the diagnosis has already been established, the appointment of insulin is postponed. Especially quickly diabetic ketoacidosis develops in young children.

In patients already receiving insulin therapy, the cause of diabetic ketoacidosis and coma may be:

Improper treatment (prescribing insufficient doses of insulin);

Violation of the regimen of insulin therapy (skipping injections, using

use of expired insulin preparations);

Gross malnutrition (in girls of puberty, sometimes deliberately in order to reduce body weight);

A sharp increase in the need for insulin, which may occur

due to infectious diseases, stress, surgical interventions, etc.

The severity of the condition in diabetic ketoacidosis is due to a sharp dehydration of the body, decompensated metabolic acidosis, severe electrolyte deficiency, hypoxia, in most cases hyperosmolarity and often concomitant intercurrent diseases.

The following biochemical disorders and pathophysiological processes lead to the development of coma in diabetic ketoacidosis:

Sudden dehydration of brain cells;

Hyperosmolarity due to hyperglycemia;

Acidosis;

The increased content of nitrogenous slags due to the decomposition of protein

cov and violations of the excretory function of the kidneys;

Severe hypoxia of the brain due to a decrease in cerebral blood flow,

an increase in the concentration of HbA 1c, a decrease in the content of 2,3-diphosphoglycerate in erythrocytes;

Insufficiency of the mechanisms of intracellular energy

security;

hypokalemia;

ICE;

General intoxication.

Treatment of diabetic ketoacidosis includes 6 major areas.

Introduction of fluid for rehydration.

The introduction of insulin to stop catabolic processes (ketoacidosis) and reduce hyperglycemia.

Correction of electrolyte disturbances.

Relief of acidosis with bicarbonates.

General activities.

Treatment of the conditions that caused diabetic ketoacidosis.

Cerebral edema is the most common cause of death. The reason for the development of cerebral edema during treatment is not completely clear, however, a too rapid decrease in intravascular osmolarity may enhance this process. In this regard, rehydration in children with diabetic ketoacidosis must be carried out more slowly and carefully than in other cases of dehydration.

The volume of injected solutions depends on the age of the child and is:

At the age of up to 1 year - 1000 ml;

1-5 years - 1500 ml;

5-10 years - 2000 ml;

10-15 years - 2000-3000 ml / day.

With glycemia more than 14 mmol / l, fluid replacement is carried out with 0.9% sodium chloride solution and Ringer's solution. With a decrease in glycemia below 14 mmol / l, a 5-10% glucose solution is added to the composition of the injected solutions to maintain osmolarity and prevent a rapid decrease in glycemia, since with a rapid drop in blood osmolarity, the osmolarity of the cerebrospinal fluid remains much higher (due to the slow exchange processes between the cerebrospinal fluid and blood). Fluid rushing into the cerebrospinal fluid along the concentration gradient can cause cerebral edema. The introduction of glucose is also necessary to eliminate the energy deficit in the body, restore glycogen content in the liver, reduce ketogenesis and gluconeogenesis.

Basic principles of insulin therapy in diabetic ketoacidosis

The initial dose of insulin is 0.1 U/kg/h; in young children, this dose can be 0.05 U / kg / h, and with severe concomitant purulent infection, it can increase to 0.2 U / kg / h.

The decrease in glycemia in the first hours should be 4-5 mmol / l / h.

If this does not happen, the dose of insulin is increased.

With the normalization of acid-base balance, the patient is transferred to subcutaneous injection of insulin every 3-4 hours. In the absence of ketosis on the 2-3rd day, the child is transferred to 5-6 times the introduction of short-acting insulin, and then to the usual combined insulin therapy.

Relief of acidosis

Gradual normalization of the acid-base state develops simultaneously with the treatment of diabetic ketoacidosis due to rehydration and insulin administration. Fluid replenishment

leads to the restoration of blood buffer systems, and the introduction of insulin suppresses ketogenesis.

Bicarbonates are used only in extreme cases:

When blood pH drops to a level that suppresses external respiration

(below 6.8), which has a negative inotropic effect on the myocardium, reduces the sensitivity of blood vessels to catecholamines, increases insulin resistance and lactate production by liver cells;

In case of violation of myocardial contractility in conditions of persistent

go shock (the latter usually develops with inadequate resuscitation and inadequate action of insulin in septic conditions).

Usually, 1-2 mmol/kg of bicarbonate (2.5 ml/kg of 4% sodium bicarbonate solution) is administered slowly intravenously (over 1 hour). Additionally, a solution of potassium chloride is administered at the rate of 0.15-0.3 g of dry matter per 1 kg of body weight per 1 liter of liquid once.

Hypoglycemia and hypoglycemic coma

The outcome of a severe hypoglycemic state can be a hypoglycemic coma, if timely measures for its relief are not taken for various reasons. Hypoglycemic coma is the cause of 3-4% of deaths in patients with diabetes. In recent years, due to the expansion of the network of self-control schools and the widespread introduction of self-control tools, the number of severe hypoglycemic conditions ending in a coma has significantly decreased.

There are 3 degrees of severity of hypoglycemic conditions.

I degree - easy. A child or adolescent is well aware of his

standing and independently stops hypoglycemia (this does not apply to children under 5-6 years old, since in most cases they are not able to help themselves).

II degree - medium. Children or adolescents cannot self-manage hypoglycemia and need outside help, but are able to take carbohydrates by mouth.

III degree - severe. The child or adolescent is in a semi-conscious, unconscious or comatose state, often in combination with convulsions, and needs parenteral therapy (intramuscular administration of glucagon or intravenous administration of glucose).

The causes of hypoglycemic conditions include errors in the administration of insulin, alcohol intake, heavy physical exertion during the day or evening hours, and skipping meals during the administration of insulin.

In table. 18-8 shows the main differences between ketoacidotic and hypoglycemic coma.

Table 18-8.Differential diagnosis of hypoglycemic and ketoacidotic coma

PREVENTION

Currently, prevention is possible in close relatives in families where there are patients with type 1 diabetes. Based on HLA typing, the risk of the disease is calculated and regular immunological examinations are carried out for the presence of antibodies to islet cells.

FORECAST

Depends on the adequacy of the treatment. While maintaining a carbohydrate metabolism rate close to normal (HbA 1c not higher than 7%), a normal life in terms of duration and quality is possible. Average life expectancy is reduced due to the development of specific complications (diabetic nephropathy and chronic renal failure, early atherosclerosis and coronary heart disease, "diabetic foot" with the development of gangrene, damage to cerebral vessels with the development of a stroke). These complications are directly related to poor DM compensation.

When the synthesis of hormones changes and the amount of androgens (male sex hormone) in a girl exceeds the available norms, virilization develops in women. Such a diagnosis is not at all pleasing, because many symptoms of the disease can deprive a girl of ordinary female happiness. It happens that male sex hormones predominate in newborn girls and treatment should be started immediately, since in the future it threatens with infertility and impaired development of the genital organs.

Virilization in women always has clearly defined symptoms that are simply impossible not to notice. Hair growth in places where they grow only in men, if it is arms, legs and nipples, then you can still put up with it, but the hair in the area of ​​\u200b\u200bthe mustache, cheeks and on the tip of the nose is a real tragedy for ladies. It is worth alerting if the timbre of the voice has changed, you notice a bald patch on your head or acne on your face.

The fact that you develop a disease is indicated by the excessive development of muscle mass. Musculature becomes masculine accordingly, and the chest loses its pomp, becoming flatter. The genital organs also change, the clitoris increases, the menstrual cycle is disturbed, and the internal genital organs also hypertrophy. During such changes, women feel a sharp increase in libido, and if you do not take any drugs for this, then increased sexual attraction should be alert.

Having noticed one of the signs of virilism, you should immediately visit a gynecologist and endocrinologist. These doctors are most often the first to make a diagnosis, because the causes of the viril syndrome are mainly diseases related to their qualifications.

The appearance of secondary male sexual characteristics in a lady, or, as they often say, masculinization, often occurs in athletes, especially those who are seriously interested in bodybuilding. Female bodybuilders strive to build huge muscles, and since this is not very common for a woman, she has to resort to the help of anabolic steroids. Preparations for muscle growth are nothing more than a synthetic male hormone, and if the androgenic activity in them is high, virilization in women occurs quite quickly.

If various neoplasms, problems with the thyroid gland or a hereditary factor have become the cause of the appearance of the viril syndrome, then this is not your fault, the situation can be corrected by starting treatment. Another thing is when a woman consciously takes steroids and often the first manifestations of male-type muscles even please female bodybuilders. Try to be careful and choose more gentle anabolics, because the initiated process of changes during neglect is irreversible.

Virilization is a pathological process in a woman's body, which is accompanied by the appearance of signs inherent in the stronger sex. It is associated with a certain group of diseases and is explained by the excessive production of androgens - male hormones. Such a violation is often observed with a disorder in the activity of the adrenal glands or ovaries. The article talks about virilization in women. What is it and why an anomaly occurs, we will consider below.

The mechanism of development of pathology

Virilization is a process that is accompanied by internal and external manifestations. The representative of the weaker sex changes appearance, voice timbre. Her physique is beginning to resemble male figure.

The menstrual cycle is interrupted. The ability to conceive disappears. In severe cases, there are no critical days. The shape of the genitals changes - the genitals of a woman become similar to men's. Such signs can be observed in a girl immediately after birth or develop much later. Virilization is a pathology in which an imbalance occurs in the body. Androgens begin to predominate over female hormones. Why does the crash occur? The basis of all substances of this kind is cholesterol. For the process of transformation of sex hormones, progesterone is also needed, which regulates the maturation of female gametes. A certain amount of this component enters the blood. The rest forms other substances. These are estrogens, which determine a woman's ability to conceive, and androgens. Such processes occur in the body of any person, regardless of their gender. However, due to certain reasons, the balance can be disturbed.

What factors contribute to the development of pathology?

It is known that a small amount of hormones characteristic of the male body is necessary for the normal development of muscles and the nervous system in girls. However, an excess of androgens is not the norm. Why do some women have their content exceeding the allowable value? This violation occurs for the following reasons:

1. Neoplasms of the adrenal glands. These include diseases that are benign in nature, as well as cancer pathologies.
2. The penetration of an excessive amount of androgens into the body of a girl. This process takes place even before birth. It is explained by the presence of neoplasms in the expectant mother.
3. Tumors of the sex glands.
4. The appearance of small cysts in the ovaries.
5. Neoplasms of other organs, which are accompanied by the production of large amounts of androgens.
6. The use of products containing male hormones or increasing their production. Such pills and injections are used by athletes to increase muscle volume and accelerate its growth. These methods lead to the fact that a woman has to seek medical help.

What are the symptoms of the disorder?

Virilization is a malfunction of the body, which is accompanied by various manifestations, for example:

Such symptoms negatively affect the physical and psychological state of the girl, reduce her self-esteem, mood. If you find these signs, you should contact a medical facility. Examination and therapy allow you to get rid of unpleasant manifestations.

Symptoms of anomalies in childhood

Virilization is a pathology that is observed both in adult girls and in young female children. In adults, the violation manifests itself in the form of minor changes in the structure of the genitals (enlargement of the clitoris). In addition, the figure of such women resembles a male physique.

In girls, external signs of anomalies become noticeable immediately after birth. Their genitals are similar to men's. The manifestations of pathology are pronounced. As a result, physicians cannot determine gender baby. Timely and adequate therapy can eliminate the symptoms of the anomaly. But in the absence of treatment, it develops further. By the age of five, hair appears in the genital area. After 2-3 years, it grows on the surface of the face. Virilization of the genital organs is observed, which is accompanied by an incorrect formation of the body. These girls have narrow hips, massive shoulders and protruding brow ridges. On the surface of the skin of the mammary glands, armpits and genitals, areas of a brown tint appear. During puberty, there is excessive growth of hair on the body, acne.

The figure of such patients is disproportionate. The limbs look very short compared to the body.

The phenomenon of virilization in girls is often associated with pathologies of the adrenal glands. In some patients, the anomaly occurs even before birth. For others, it manifests itself at a later period.

The degree of development of pathology

A. Prader, a Swiss specialist in the field of endocrinology, created a scale for determining the stage of anomalies in girls. The severity of the stages is determined by how similar the genitals of the female child are to the male. There are the following degrees of virilization:

1. Initial. The clitoris is slightly hypertrophied. The labia are sufficiently developed, the entrance to the vaginal area is slightly narrowed.
2. Second stage. It is characterized by a significant increase in the volume of the clitoris. The labia are poorly developed. The entrance to the vaginal area is greatly reduced.
3. Third stage. The clitoris becomes like a penis, the foreskin and head appear. The labia are deformed. The urethra and vagina have one opening.
4. Fourth degree. The labia are fused. The skin in this area is covered with folds and becomes dark in color.
5. Fifth degree. At this stage of virilization of the external genitalia, the clitoris almost does not differ from the penis. Despite its presence, the patient has no testicles.

The manifestation of pathology in the representatives of the stronger sex

Usually, an anomaly is associated with malfunctions in the female body. But there are cases of development of virilization in men. It is also associated with excessive androgen production. Such boys from birth are distinguished by a large physique, they grow rapidly. But by about the age of ten, physical development slows down. The child already has the figure of an adult man, looks older than his peers. As a rule, the patient's height does not exceed 160 cm. Virilization is associated with early hair growth on the body and face, coarsening of the voice, and acne. The child is embarrassed by the appearance of such signs and needs medical attention.

In adults, the anomaly is accompanied by changes in the emotional background (apathy, low mood, aggression). Sleep disturbances occur, constant fatigue is observed. The hairline on the body becomes thick, and on the head - rare.

Men who have this disorder have high risk development of hypertension and malignant neoplasms of the prostate gland.

Hirsutism: signs and causes

The anomaly consists in the excessive growth of hair on some parts of the body (on the surface of the face, back, mammary glands, abdomen, thighs). This phenomenon is accompanied by a failure in the cycle of menstruation, acne. Hirsutism and virilization are in most cases related and are due to excess production of male hormones. Hair with this pathology grows in those parts of the body where women should not have them.

The reasons for the anomaly are:

1. Neoplasms of the adrenal glands and ovaries.
2. Cushing's disease.
3. Lack of thyroid hormones.
4. The use of certain medications.
5. Benign neoplasm of the pituitary gland.
6. Polycystic gonads.

Sometimes hirsutism is hereditary. In persons of Caucasian nationalities and inhabitants of the Mediterranean states, this phenomenon is quite common.

Diagnosis of pathology

If signs of virilization are found, it is necessary to consult a specialist. The examination allows to identify the causes of the anomaly.

Diagnosis includes an analysis of the content of hormones in the blood, an assessment of the condition of the internal genital organs and adrenal glands using ultrasound, CT and MRI.

Methods of therapy

Depending on the results of the examination, specialists select a method of treating the pathology. There are several options: