Hypogonadotropic hypogonadism: symptoms, treatment. Differential diagnosis of hypogonadism

GENERAL HYPOFUNCTION IN BOYS

7.3.1. hypogonadism in males, it develops as a result of a persistent, often irreversible decrease in testosterone secretion. Common causes of hypogonadism in children may be associated with intrauterine or postnatal gonadal damage - primary or hypergonadotropic hypogonadism; isolated or in combination with other tropic hormones, impaired secretion of gonadotropins as a result of congenital or acquired damage to the pituitary gland ( secondary hypogonadism) or hypothalamus ( tertiary hypogonadism). The last two forms are characterized by a decrease in the secretion of gonadotropins and are sometimes combined under the name hypogonadotropic hypogonadism. Hypogonadism can be an independent disease (isolated hypogonadism), or one of the symptoms in the structure of congenital or acquired, including endocrine diseases ( symptomatic hypogonadism). Sometimes in children and adolescents, hyperprolactinemic hypogonadism(Chapter 9). The causes and clinical features of the most common forms of hypogonadism are shown in Table 7.12.

Table 7.12.

Classification and characteristics of the main forms of hypogonadism in boys.

Form name	Etiology

1. Congenital anorchia (anorchism syndrome).	Intrauterine, possibly genetically determined lesion of the testicles.
2. Primary testicular hypoplasia	The etiology is unknown. Assume the possibility of congenital and acquired forms.
	Karyotype 47,XXY, 48,XXXY, 49,XXXXY (Joseph syndrome) or mosaicism. It occurs with a frequency of 1:500 males.
	Genetically determined defects in testosterone biosynthesis.
5. Noonan syndrome	Frequency 1:16000 males. Autosomal dominant inheritance pattern, but normal karyotype.
	X-linked inheritance is assumed.
	It develops as a result of surgical or traumatic castration, viral orchitis ( parotitis, Koksaki B, ECHO, etc.), radiation or drug lesion gonad..
II. HYPOGONADOTROPIC (SECONDARY AND TERTIARY) HYPOGONADISM
	It is inherited in an autosomal recessive manner. It is most often caused by a violation of GH secretion as a result of blocking mutations in the GRH receptor gene, leading to impaired binding of GRH to the receptor on gonadotropin-secreting pituitary cells. Perhaps some patients have a variant of the Kallmann syndrome.
b) with reduced LH production (Paskuliany syndrome, fertile eunuch syndrome)	Caused by LH deficiency of the pituitary gland due to a mutation in the gene b - LH subunits.
	Caused by a deficiency of pituitary FSH due to a mutation in the gene b -FSH subunit, leading to inability to bind to a -subunit and form an active hormone.
2. Idiopathic hypogonadotropic hypogonadism
3. Adiposo-genital dystrophy (Babinsky-Frelich syndrome)	It develops as a result of infectious, traumatic, including surgical, radiation injury CNS, but more often the cause is a tumor of the hypothalamic-pituitary brain, histiocytosis X. It can develop in patients with hemochromatosis and thalassemia major.
4. Kallmann syndrome I, II and III.	Type I is caused by mutations in the KALIG1(Xp22.3) gene. The type of inheritance is autosomal recessive. In type II, genetic heterogeneity is noted, with III type- X-linked recessive and autosomal dominant types of inheritance. In all cases, the migration of GnRH neurons to the olfactory bulbs and further to the hypothalamus is impaired. There is no defect in the GRH gene.
5. Prader-Willi Syndrome	Most have a paternal chromosome 15q 11.2-q13 deletion or disomy of the same maternal chromosome 15 fragment. Frequency - 1:25000.
6. Laurence-Moon syndrome.	A disease with an autosomal recessive mode of inheritance.
7. Bardet-Biedl syndrome.	A disease with an autosomal recessive mode of inheritance. There are three genetic forms: BBS1 mapped 11q; BBS2-16q21; BBS3 -3p.
8. Hypopituitarism	One of the hereditary variants is due to mutations in the PROP1 gene, leading to impaired differentiation of adenohypophysis cells, including gonadotrophs (Chapter 1).
9. Rod Syndrome	Sex-linked recessive or dominant type of inheritance.
10. Syndrome Meddok.	Mutations in the DAXI gene, which controls embryonic development arcuate nuclei of the hypothalamus and adrenal glands.
11. Other forms of hypogonadism.	Hypogonadism in hermaphroditism, etc.
III. HYPERPROLACTINEMIC HYPOGONADISM
	It is rare in boys.

Clinic different forms of hypogonadism is quite monotonous and depends on the age of the patient and the time of onset of the disease. The volume of the testicles in boys is reduced, they can be located in the scrotum, but more often the first symptom of congenital hypogonadism is the extrascrotal location of the testes (unilateral or bilateral cryptorchidism). Sometimes the testicles are aplastic, often have a dense or flabby texture, in puberty they do not increase. The penis is reduced in size, the scrotum is without folds, tightened, secondary sexual characteristics at puberty are absent or weakly expressed.

Androgen deficiency leads to the gradual formation of extragenital symptoms of hypogonadism: eunuchoidism, obesity, decreased bone and muscle mass, often tall. Eunuchoid proportions of the body are characterized by elongation of the limbs with a relatively short torso, the predominance of the width of the pelvis over the width of the shoulders. Obesity can occur as early as prepubertal age, but more often small degree, since an increase in fat mass is combined with poor muscle development and a decrease in bone mass. Typical redistribution of adipose tissue according to the feminine type with predominant deposition in the thighs, abdomen, chest (false gynecomastia), sometimes there is true gynecomastia. As a rule, patients grow normally in childhood, but due to a delay in bone formation and a lag in skeletal differentiation, growth continues longer than usual and their final height may be high. Muscles are weak, flabby. Extragenital signs of hypogonadism usually begin to form at 9-12 years of age and become apparent in adolescents over 13-14 years of age, rarely at an earlier age.

Symptomatic hypogonadism more often diagnosed at an early age, and the basis for the diagnosis of the disease is usually a combination of a number of phenotypic signs, malformations and symptoms not due to hypogonadism. Clinical Features different forms of hypogonadism are given in tables 7.13., 7.14.

Table 7.13.

Most common symptoms hypogonadism in boys.

	Symptoms
infant	Cryptorchidism · Micropenis · Hypoplasia of the scrotum · Some stigmas of disembryogenesis and malformations characteristic of symptomatic hypogonadism.
prepubertal	· Accelerated (rarely slow or moderate) growth Obesity · Some stigmas of dysembryogenesis, psychomotor retardation and malformations characteristic of symptomatic hypogonadism.
Pubertal	· Cryptorchidism, microgenitalism · No enlargement of the testicles and external genitalia · Lack of secondary sexual characteristics · Disproportionate (usually eunuchoid) physique. Gynecomastia
adults	· Reducing the size of the testicles · Involution of secondary sexual characteristics · Obesity with a feminine type of fat deposition Gynecomastia · Lack of erections

Table 7.14.

Characteristics of the main forms of hypogonadism in boys.

Form name	Size and location of the gonads	external genitalia	secondary sexual characteristics	Other symptoms
I. HYPERGONADOTROPIC (PRIMARY) HYPOGONADISM
1. Congenital anorchia (anorchism syndrome)	The testicles in the scrotum and inguinal canals are absent from birth.	At birth, the external genitalia are formed correctly, regular sizes, but sometimes the size of the penis and scrotum are reduced.	Puberty absent at puberty, but sometimes there is scanty sexual hair growth	Pre-puberty average growth, masculine physique. In prepubertal and pubertal age, obesity appears, acceleration of growth, eunuchoid body type is formed. Intelligence is normal.
2. Primary testicular hypoplasia	At birth, the testicles are in the scrotum. Sometimes at an early age there is dropsy of the testicles. In prepubertal age, pseudoretention of the testicles is typical with normal or reduced sizes. Testicular hypoplasia becomes apparent at puberty.	The external genitalia are formed correctly. At prepubertal age, their sizes are normal or reduced, but there is no increase in their size at puberty.
3. Klinefelter's syndrome and other similar syndromes	At puberty, the most typical sign is reduced and dense testicles. Sometimes there is cryptorchidism at birth.	In most cases, the development of the penis and scrotum is normal and there are pubertal changes. Sometimes microgenitalism is possible.	Secondary sexual characteristics may be normal, poorly developed, or absent. At puberty, tall stature, obesity, gynecomastia, and eunuchoidism are typical.	In prepubertal age, accelerated growth and behavioral disorders are noted. In adult men, infertility is almost always found.
4. Primary Leydig cell deficiency	Testicles are reduced, the cryptorchidism is possible.	At birth, the external genitalia are formed correctly, there is no pubertal enlargement.	The clinic of eunuchoidism with obesity, underdevelopment of the genital organs, the absence of sexual hair growth is formed at puberty.
5. Noonan syndrome	Some boys may have cryptorchidism.	There may be a micropenis and scrotal hypoplasia.	In some patients, the clinic of eunuchoidism is formed at puberty.	Pterygoid folds on the neck, triangular face, hallux valgus elbow joints, short stature, lymphatic edema of the hands and feet, ptosis, sunken rib cage, defects of the right parts of the heart, mental retardation.
6. Primary tubular failure (Sertoli cell del Castillo syndrome)	The disease in childhood is not diagnosed, since there are no deviations in sexual and physical development. In adolescents and adults, a decrease in the size of the testicles is noted with normal development external genitalia and secondary sexual characteristics. Cryptorchidism is rare. Diagnosed in adults with infertility.
7. Acquired forms of anorchism or testicular hypoplasia	If it occurs before puberty, there are no signs of puberty. In adults, involution of secondary sexual characteristics occurs, obesity and eunuchoidism are formed.

1. Isolated (idiopathic) hypogonadotropic hypogonadism (IGH) a) with reduced production of LH and FSH b) with reduced LH production (Paskuliany syndrome, fertile eunuch syndrome) c) with reduced production of FSH	Most often, unilateral or bilateral cryptorchidism with inguinal dystopia of hypoplastic testicles is detected. In some cases, there is only a decrease in the size of the testicles, and in isolated LH deficiency, the size of the testicles may be normal.		In prepubertal age, obesity is typical, in the future - eunuchoidism, lack of puberty.	Patients are often tall, the intellect is normal.
2.Adipose-genital dystrophy (Babinsky-Frelich syndrome)	Testicles at birth in the scrotum, in adolescents their size is reduced, pseudo-retention is possible.	Adolescents do not have pubertal changes, adults usually do not have erections, the wrinkling and pigmentation of the scrotum disappears.	Or disappear	Hypogonadism, as a rule, is combined with obesity, decreased growth rate, sometimes hypothyroidism, diabetes insipidus, visual impairment, neurological symptoms in various combinations.
3. Kallmann syndrome I, II and III.	Most often, unilateral or bilateral cryptorchidism with inguinal dystopia of hypoplastic testicles is detected. In some cases, there is only testicular hypoplasia.	At birth, micropenis and underdevelopment of the scrotum are revealed. At puberty, there is no increase in them.	In all variants of the syndrome, there are no secondary sexual characteristics and there is anosmia as a result of agenesis of the olfactory centers of the brain. Besides, in type I there are bilateral synkinesia, ataxia, kidney agenesis; in type II - mental retardation, choanal atresia, sensorineural deafness, heart defects, short stature; in type III - cleft lip and palate, hypotelorism, kidney agenesis.
4. Prader-Willi Syndrome	Bilateral cryptorchidism and testicular hypoplasia from birth.		No secondary sexual characteristics	At an early age, there is muscle hypotonia up to atony, a decrease in reflexes. From 2-3 months, polyphagia appears, high pain threshold, oligophrenia. From 1-1.5 years, diencephalic obesity develops, and in adolescence- diabetes.
5. Laurence-Moon syndrome.		The penis and scrotum are sharply hypoplastic, there are no pubertal changes.	No secondary sexual characteristics	Typical signs manifest in the first years of life - oligophrenia, spastic paraplegia, pigmentary retinopathy.
6. Bardet-Biedl syndrome.	Bilateral cryptorchidism and microorchidism from birth.	The penis and scrotum are sharply hypoplastic, there are no pubertal changes.	No secondary sexual characteristics	Obesity, oligophrenia, polydactyly, retinopathy pigmentosa are typical.
7. Hypopituitarism	At congenital forms sometimes there is cryptorchidism and microorchidism. At puberty, there is no enlargement of the testicles.	In congenital forms, there is usually a micropenis and scrotal hypoplasia. There are no pubertal changes.		Mandatory symptoms in childhood are growth retardation with a lag in bone age. In adolescents and adults, the clinic of adipose-genital dystrophy.
8. Rod Syndrome	Some patients have bilateral cryptorchidism and microorchidism from birth.		In most boys, the clinic of hypogonadism appears only at puberty. Secondary sexual characteristics are absent or scarce.	Persistent symptom- congenital ichthyosis. There may be mental retardation and epilepsy.
9. Syndrome Meddok.	Bilateral cryptorchidism and microorchidism from birth. Some patients do not have cryptorchidism.	The penis and scrotum are hypoplastic, there are no pubertal changes.	Secondary sexual characteristics are absent or scarce.	Symptoms of primary congenital adrenal insufficiency (see Chapter 4).
10. Other forms of symptomatic hypogonadism.	The clinical picture is determined by the underlying disease.
III. HYPERPROLACTINEMIC HYPOGONADISM
1.Micro- or macroprolactinoma.	In boys, the symptoms of hyperprolactinemic hypogonadism are varied. In some cases, there is growth retardation, microgenitalism, and the absence of signs of sexual development at puberty. In some adolescents, microgenitalism is combined with early sexual hair growth, medium or high growth, eunuchoidity, gynecomastia. Perhaps a combination of hypogonadism, obesity with the distribution of fat according to the Cushingoid type and pink striae. Most patients complain of weakness, excessive weight gain, drowsiness. By the time of diagnosis, more than 80% of patients have neurological and visual impairments.

Laboratory criteria for various forms of hypogonadism are presented in Table 7.15.

Table 7.15.

Laboratory diagnosis of hypogonadism

Form of hypogonadism	Karyotype	Basal levels of hormones in the blood				The results of functional tests with hCG
Form of hypogonadism	Karyotype	LG	FSH	BRL		with 1 injection	with 3-5 injections
I. HYPERGONADOTROPIC (PRIMARY) HYPOGONADISM
1. Anorchism Syndrome*	46,XY				¯¯	neg.
2. Primary testicular hypoplasia	46,XY			N or	¯¯		neg.
3. Klinefelter's syndrome and other similar syndromes	47,XXY, 48,XXXY, 49,XXXXY or mosaic	N, ¯ or			N or ¯	neg.	+ or ±
4. Primary Leydig cell deficiency	46,XY		N , or		¯¯	neg.	neg.
5. Noonan syndrome	46,XY				¯¯		neg.
6. Primary tubular failure (Sertoli cell del Castillo syndrome)	46,XY	N, or			N or ¯	+ or ±	+ or ±
7. Acquired forms of anorchism or testicular hypoplasia	46,XY				¯¯
II. HYPOGONADOTROPIC (SECONDARY AND TERTIARY) HYPOGONADISM
1. Isolated hypogonadotropic hypogonadism (IGH)
a) with reduced production of LH and FSH	46,XY	¯¯	¯¯	N or ¯	¯¯		+ or ±
b) with reduced LH production	46,XY	¯¯		N or ¯	¯¯		+ or ±
c) with reduced production of FSH	46,XY		¯¯	N or ¯	¯¯		neg. or ±
2.Adiposogenital dystrophy	46,XY	¯¯	¯¯	N, or ¯	¯¯		+ or ±
3. Kallmann syndrome I, II and III.	46,XY	¯¯	¯¯	N or ¯	¯¯	Neg.	+ or ±
4. Symptomatic hypogonadism.	46,XY	¯¯	¯¯	N or ¯	¯¯		neg. or ±
5.Hypopituitarism	46,XY	¯¯	¯¯	N, or ¯	¯¯		+ or ±
III. HYPERPROLACTINEMIC HYPOGONADISM
1.Micro- or macroprolactinoma.	46,XY

· In pre-pubertal boys, gonadotropin levels may be slightly elevated.

Algorithm for the differential diagnosis of hypogonadism

7.3.2. delayed sexual development (ZPR) is defined as a functional, tempo delay in the appearance of signs of puberty by more than 2 years compared with the average terms, i.e. ZPR is characterized by temporary, only during puberty, androgen deficiency. The causes of ZPR depend on the constitutional characteristics of the individual (family form) - the late maturation of the gonadostat (the system that regulates the function of the gonads) and target tissue receptors that interact with gonadotropic and sex hormones. In some boys, the cause of ZPR can be severe chronic somatic (diseases of the cardiovascular system, gastrointestinal tract, lungs, liver, blood, etc.) or endocrine (obesity, hypothyroidism, thyrotoxicosis, hypoparathyroidism, diabetes mellitus, etc.) pathology, as well as diseases of the central nervous system (consequences of trauma, infection, hypoxia). Sometimes there is a combination of reasons.

ZPR, unlike hypogonadism, is diagnosed only in adolescents from 13.5-14 to 16-17 years old, although it is possible to assume the possibility of retarded puberty (threatened by ZPR) in children 9-11 years old. Often one or both parents in the family or older siblings had a delayed sexual development. Characterized by a decrease in the size of the external genitalia and testicles, although their size corresponds to normal for prepubertal age, the later appearance of secondary sexual characteristics. The main symptoms and laboratory findings in various forms ZPR in boys are shown in Table 7.16.

Table 7.16.

Classification and characteristics of the main forms of delayed sexual development in boys

Form name	Characteristic	Laboratory data
1. Constitutional.	A familial form of DDD, usually associated with growth retardation, but sometimes growth can be moderate. Body weight is normal or low. masculine physique, somatic pathology No. The external genitalia are formed correctly, but correspond to prepubertal ones. Often, in boys over 9-11 years old, testicular pseudo-retention persists. There are no secondary sexual characteristics at puberty.	The levels of gonadotropic hormones and testosterone in the blood correspond to prepubertal values. Tests with single and triple administration of human chorionic gonadotropin are positive. Puberty begins at 15-17 years or later, its pace is normal. "Bone" age lags behind the passport age by 2-3 years.
2.Somatogenic.	Develops against the background of severe somatic or endocrine pathology. The clinic determines the underlying disease. You should always keep in mind the possibility of malnutrition, hypovitaminosis, deficiency of minerals and trace elements. Typically, the correct structure of the external genitalia and the absence of signs of puberty at puberty.	Same. The degree of lag of "bone age" from the passport depends on the severity and duration of the disease.
3. False adipose-genital dystrophy.	It develops in boys with lesions of the central nervous system of infectious, hypoxic or traumatic genesis, which arose at any age, but more often in the perinatal period. Unlike adipose-genital dystrophy, disorders of the hypothalamic-pituitary-gonadal system have transitory nature and are usually associated with chronic infections (tonsillitis) and obesity. Characterized by obesity with a feminine type of fat deposition, accelerated growth, microgenitalism, pseudo-retention of the testicles, the absence of secondary sexual characteristics at puberty.	Decreased levels of testosterone and gonadotropic hormones. Tests with single and triple administration of human chorionic gonadotropin are positive. Puberty begins after 15-16 years.
4. Irregular puberty syndrome.	It is characterized by the appearance of early or timely sexual hair growth as a result of adrenal hyperandrogenism with infantile sizes of the testes and external genitalia. Always accompanied by obesity.	LH levels are elevated or normal, FSH and testosterone levels are low. Increased levels of ACTH, cortisol and adrenal androgens (DEA and DEAS). Often determine moderate hyperprolactinemia. The test with chorionic gonadotropin is weakly positive.

ZPR is more often an independent syndrome, but it can be one of the symptoms (sometimes the only one) of hypogonadism. Since hypogonadism requires long-term, often life-long, replacement therapy, the differential diagnosis with prepubertal and pubertal dysrhythmias becomes important. However, clinical and laboratory data do not always allow reliable differentiation of some forms of the disease, for example, isolated hypogonadotropic hypogonadism and pseudogenital dystrophy. Therefore, it is important to monitor the patient and the effectiveness of treatment in dynamics and re-examination.

Table 7.17.

Differential diagnosis of some forms of hypogonadism and mental retardation.

Symptoms	Primary testicular hypoplasia	IGG	ZPR of constitutional-somatogenic genesis	False AGD
Height	Average or above average		Detained	Average or above average
Body mass	Average. Begins to increase at puberty.	Obesity from an early age.	More often average or deficiency of body weight.	Obesity from an early age.
Violations of the gonads and external genital organs.	Reducing the size of the testicles, often cryptorchidism, micropenis.		There is no cryptorchidism (pseudoretention of the testicles is possible). The size of the gonads and external genitalia correspond to prepubertal age.
secondary sexual characteristics	No signs of puberty at puberty
"Bone Age"	Corresponds to the passport		Behind the passport	Corresponds to the passport
Test by 1-fold administration of hCG	Negative	More often negative	More often positive
Test with 3-5 times the introduction of hCG	Negative	Weakly positive or questionable	Positive
circadian rhythm LH, FSH and T	Absent	Absent	Appears 1-2 years before puberty
PRL level in the blood	Elevated or normal	lowered	Normal
Test with nafarelin	Do not spend	negative	Positive
Test with thyroliberin	Do not spend	negative	Positive

Treatment. Boys with hypergonadotropic hypogonadism in pre-pubertal age, if penis size correction is necessary, anabolic steroids are treated at age-specific doses until the desired result is obtained. The rudiments of the gonads are removed or, if possible, brought into the scrotum.

Starting from the age of 12-13, permanent replacement therapy with testosterone preparations is prescribed. The main drugs are shown in table 7.18.

Table 7.18.

Pharmacokinetics of testosterone preparations.

A drug	Release form	Effective dose (for adults)		Mean circulation time in blood	Note
Oral preparations
Mesterolone (Proviron-25) - metabolite 5 a-DHT	Tablets 25 mg		75-150 mg/day in 3 divided doses		It does not undergo primary hepatic metabolism when taken orally, it replaces only DHT-dependent functions, i.e. there is no full spectrum of T effects required for long-term replacement therapy.
Testosterone undecanoate (Andriol) - ether natural testosterone	Capsules 40 mg		80-120 mg/day in 3 divided doses		It does not undergo primary hepatic metabolism, but has a short half-life, which requires frequent administration of the drug in obviously high doses.
T-cyclodextrin - natural testosterone ester	Capsules 40 mg		80-120 mg/day in 3 sublingual doses		Due to the presence of a cyclodextrin shell, it is slower than andriol to be metabolized in the body. Otherwise, it does not differ from andriol.
Preparations for intramuscular injection
Tetrasterone (Sustanon-250, Omnadren-250) - a combination of 4 testosterone esters	Ampoules 250 mg in 1 ml oil solution		250 mg IM once every 3-4 weeks		24-48 hours after administration, the concentration of testosterone in the blood increases sharply, gradually decreases by 10-14 days and reaches the initial level by 21 days. Most frequent side effect- gynecomastia.
Testenat 10% (Testoviron-Depo-100) (Testosterone enanthate 0.11 and testosterone propionate 0.024).	Ampoules 100 mg in 1 ml oil solution		100 mg IM once every 10-14 days		The need for relatively frequent injections complicates the use of the drug.
Testosterone undecanoate	Ampoules 1000 mg in 1 ml oil solution		1000 mg IM once every 6-8 weeks		It has a long period half-life (up to 8 weeks), and the initial peak concentration is low, which avoids complications.
Testosterone bucyclate	Ampoules 500 and 1000 mg in 1 ml aqueous suspension		500-1000 mg IM once every 3 months		The most acceptable drug for permanent replacement therapy.
Preparations for transdermal use
Androderm, andropach - a patch for application to any area of the skin, except for the scrotum.		Contains 10 or 15 mg of natural testosterone, which maintains the physiological concentration of the hormone throughout the day. The patch is changed daily in the morning.			Skin irritation occurs in 10% of patients.
Testoderm (TTS) - patch for application to the scrotum
Andractim (2% DHT in hydroalcoholic gel)		Apply to the chest or abdomen 1 time in 2-3 days.			The gel does not provide the full spectrum of testosterone effects.

It is advisable to start substitution treatment with the introduction of long-acting or medium-acting testosterone preparations with their intramuscular use, for example, tetrasterone (sustanon-250) is administered starting with 50 mg once a month. Every 6-12 months single dose increase by 50 mg, and from 16-17 years of age continue treatment at a full replacement dose for adults (250 mg / m 1 time in 3-4 weeks). The dose of the administered drug is controlled according to clinical symptoms - it is necessary that the growth rate, physique, the degree of development of secondary and tertiary sexual characteristics correspond to the average age indicators - and normalization of the level of testosterone and gonadotropins in the blood for 7-10 days after the administration of the drug. Treatment complications are rare. With an excessive dose, fluid retention and swelling of the face and extremities are possible within 5-7 days after the administration of the drug, as well as the development of gynecomastia as a result of increased conversion of testosterone to estradiol. The most serious complication is liver damage, which is more common when large doses of drugs are taken orally. In adults, oral androgens may be recommended as maintenance therapy, with regular monitoring of liver function, or the use of transdermal applicators. For cosmetic purposes, testicular prostheses can be implanted at puberty.

At hypogonadotropic hypogonadism, if there is cryptorchidism, patients of prepubertal age are prescribed chorionic gonadotropin (Profasi, chorionic gonadotropin), which has LH activity, intramuscularly in a single dose of 1000 U/m 2 body surface 2-3 times a week for 5-6 weeks or GRG preparations (cryptocurs) intranasally 3-4 times a day for 6 weeks. If necessary, the course of treatment is repeated after 2-3 months. If cryptorchidism persists against the background of conservative treatment, surgical reduction of the testicles is indicated.

As a replacement therapy, starting from the age of 12-13, testosterone preparations are usually used, as in primary hypogonadism. Treatment with chorionic gonadotropin (IM in a single dose of 1000 U/m 2 body surface 2-3 times a week), or synthetic gonadotropins (Humegon, Pergonal, Neopergonal in a single dose of 25-75 IU intramuscularly 2-3 times a week) can be carry out courses of 2-2.5 months with a break of 1-1.5 months, however, due to the rapid decrease in the effect, the use of these drugs with a substitution purpose is not justified. Prescribing HGH drugs requires special equipment: gonadorelin is effective in patients with tertiary hypogonadism with impulse, every 2 hours intravenous administration using automatic dispensers.

Boys with mental retardation are given a complex of health-improving measures (good nutrition, vitamin therapy, hardening, exercise therapy, sanitation of foci of infection), which contribute to the stimulation of physical development. Patients with obesity are prescribed a hypocaloric diet. Up to 14-15 years of age, treatment that stimulates puberty includes courses of vitamins B 1 , B 6 , E, zinc preparations. If there is no clear effect from these measures, adolescents over 14-15 years old who do not have signs of puberty additionally undergo hormonal correction, depending on the form of delayed sexual development. With a low level of gonadotropic hormones (false adipose-genital dystrophy), 1-2 courses of chorionic gonadotropin, 1000 U / m 2 of body surface, 10-15 injections, can be prescribed). It is possible to use depot testosterone preparations (omnadren, sustanon) 50-100 mg intramuscularly 1 time in 4 weeks for 3-6 months. Sometimes courses of gonadotropins alternate with testosterone preparations. An obligatory condition for the treatment of ZPR is the use of minimum doses drugs and their long-term use.

With somatogenic ZPR form treatment with hormonal drugs can be effective only if the underlying disease is compensated.

RCHD (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical Protocols of the Ministry of Health of the Republic of Kazakhstan - 2017

46.xx true hermaphrodite (Q99.1), hypopituitarism (E23.0), testicular hypofunction (E29.1), testicular hypofunction occurring after medical procedures(E89.5), Androgen resistance syndrome (E34.5), Klinefelter's syndrome, unspecified (Q98.4), Klinefelter's syndrome, karyotype 47,xxy (Q98.0), Turner's syndrome (Q96)

Pediatrics, Pediatric Endocrinology

general information

Short description

Approved
Joint Commission for Quality medical services
Ministry of Health of the Republic of Kazakhstan
dated August 18, 2017
Protocol No. 26

hypogonadism- a syndrome caused by a decrease (absence) of gonadal function or congenital disorder sensitivity of peripheral tissues to the action of sex hormones.
NB! Hypogonadism is a state of permanent absence of puberty, which must be distinguished from delayed puberty.
Hypogonadism caused by damage to the gonads is called primary or hypergonadotropic, because it is accompanied by increased production of gonadotropins. However, this reaction of the pituitary gland is typical only for adolescents and adults. In children of prepubertal age (on average, up to 10 years) with primary hypogonadism, the production of gonadotropins does not increase; corresponds to the norm, and therefore this variant of hypogonadism is called normogonadotropic. The latter is sometimes found in adults.

INTRODUCTION

ICD-10 code(s):

ICD-10
Code	Name
E29.1	testicular hypofunction
E34.5	androgen resistance syndrome
E23.0	hypopituitarism
E89.5	testicular hypofunction following medical procedures
Q96	Turner syndrome
Q98.0	Klinefelter's syndrome, karyotype 47,XXY
Q98.4	Klinefelter syndrome, unspecified
Q99.1	46,XX true hermaphrodite

Date of development/revision of the protocol: 2014 (revised 2017).

Abbreviations used in the protocol:

Protocol Users: endocrinologists, pediatricians, pediatric urologists, pediatric gynecologists, andrologists.

Evidence level scale:

A	High-quality meta-analysis, systematic review of RCTs, or large, very low probability RCT (++) systematic error the results of which can be generalized to the relevant population.
IN	High-quality (++) systematic review of cohort or case-control studies or High-quality (++) cohort or case-control studies with very low risk of bias or RCTs with low (+) risk of bias, the results of which can be generalized to the appropriate population .
WITH	Cohort or case-control or controlled trial without randomization with low risk of bias (+). The results of which can be generalized to the appropriate population or RCTs with a very low or low risk of bias (++ or +), the results of which cannot be directly generalized to the appropriate population.
D	Description of a case series or uncontrolled study or expert opinion.
GPP	Best Clinical Practice.

Classification

Classification of hypogonadism in children

Form of hypogonadism	Damage level	Sex hormone levels	FSH and LH levels
Primary: congenital acquired	Gonads	Low/Low-Normal	High/Normal
Secondary: congenital acquired	Pituitary	Short	Low/Low-Normal
Tertiary: congenital acquired	Hypothalamus	Short	Low/Low-Normal

Diagnostics

METHODS, APPROACHES AND DIAGNOSIS PROCEDURES

Diagnostic criteria
Complaints and anamnesis:
lack of testicles in the scrotum;
No signs of puberty
abnormal structure of the external genitalia;
small size of the penis and testicles;

growth retardation in pubertal children.

Physical examination:
In boys, depending on the etiology of hypogonadism, one or a combination of the following symptoms may occur:
growth retardation at puberty (in children of prepubertal age, growth is normal);
lack of testicles in the scrotum (cryptorchidism);
no signs of puberty after 14 years;
irregular (hermaphroditic) structure of the external genitalia;
small size of the penis and testicles for a given age;
dystopia of the external opening of the urethra;
The presence of the urogenital sinus;
Lack of smell.

For girls:
retardation in growth since birth / from adolescence;
no signs of puberty after 13.5 years;
Incorrect structure of the external genitalia.

Laboratory research:
· karyotype determination the presence of a child irregular structure external genitalia is an absolute indication.
Karyotype 45, XO indicates the presence of Shereshevsky-Turner syndrome. Mosaic forms of the syndrome are also possible, for example, karyotype 45, XO / 46, XX in different percentages of XX and XO clones or 45, XO / 46, XX / 46, XY (the so-called mixed gonadal dysgenesis), etc.
The detection of the karyotype 46, XY in a child with hermaphroditic genitalia (sometimes having testicles) indicates a congenital decrease / lack of sensitivity of peripheral tissues to their own androgens - a syndrome of incomplete testicular feminization.
It should be borne in mind that the karyotype 46, XY can also be found in "girls" with hypogonadism - a syndrome of complete testicular feminization.
Tall boys with delayed puberty, small testicles, and learning difficulties tend to have Klinefelter syndrome - 47 XXY and other variants with extra X chromosomes.

· hormonal profile study:
- the level of LH, FSH - in children of both sexes
- the level of testosterone (in boys), estradiol (in girls).

For primary hypogonadism:
In children of prepubertal age, there are no changes in the hormonal profile;
Elevated/normal levels of LH/FSH during puberty
The levels of testosterone and estradiol are always reduced.

For secondary and tertiary hypogonadism at any age in both sexes is characterized by:
Decrease in both LH and FSH, and estradiol (in girls), testosterone (in boys).
NB! In boys, hypogonadotropic hypogonadism is best diagnosed by testing with human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (triptorelin 0.1).

Test with HCGH
It is carried out in boys to assess the functional state of the testicles.
A three-day test is used with intramuscular administration of hCG and a subsequent study of testosterone levels 24-48 hours after the last injection.
Doses of HCG:
500 IU - with a body weight of less than 5 kg;
1000 IU - with a body weight of 5-10 kg;
1500 IU - with a body weight of 10-15 kg;
3000 IU - with a mass of more than 15 kg.
Interpretation: an increase in testosterone secretion against the background of the introduction of hCG excludes the presence of primary hypogonadism, i.e. indicates secondary hypogonadism (about the pituitary level of the lesion).
NB! To the test: suspicion of primary hypogonadism at low levels of LH, FSH.

Stimulation test with GnRH
After determining the basal levels of LH and FSH, short-acting gonadoliberin is administered and the levels of LH and FSH are determined 1 hour and 4 hours after drug administration.
Drugs used: Triptorelin 0.1 µg s.c. (AI), Buserelin 100–300 µg intranasally (BII).
Interpretation: LH level rise above 10 mU/l eliminates secondary hypogonadism and indicates tertiary hypogonadism.
NB! With a constitutional delay in puberty, with a bone age of less than 13 years in girls and 14 years in boys, a negative test with GnRH requires a second test after 1-2 years. There are no similar tests for girls.

· determination of the level of anti-Mullerian hormone (AMH) in blood serum - its detection in sufficient quantities indicates the presence of testicles in the body (with anorchism, the hormone is not detected).
Instrumental research:
Ultrasound of the scrotum, inguinal canals, abdominal cavity- in order to clarify the presence of testicles, their size and localization; the type of structure of the internal genital organs is established;
Ultrasound of the pelvic organs - in order to clarify the presence and size of the ovaries, uterus, tubes, upper third vagina;
Contrast-enhanced MRI of the pituitary gland established diagnosis secondary/tertiary hypogonadism is carried out;
X-ray of the left bone - to determine the rate of ossification;

NB! With primary hypogonadism, the lag in bone age is typical for children of both sexes only older than 9-10 years.
The lag in the rate of ossification, starting from prepubertal age, is observed in children with secondary hypogonadism in the presence of concomitant growth hormone deficiency.

Indications for expert advice:
consultation of a pediatric urologist:
- with a hermaphroditic structure of the external genitalia - to participate in deciding on the choice of the most appropriate passport sex and the implementation of surgical correction of the internal and external genitalia;
- with cryptorchidism - for surgical reduction of the testicles;
- with complaints of pain in the abdomen and in the region of the inguinal canals - to determine indications and perform emergency surgical intervention;
· consultation of a psychologist - for professional psychological support of a child and parents with a hermaphroditic structure of the external genitalia;
consultation pediatric gynecologist- with a hermaphroditic structure of the external genitalia to participate in deciding on the choice of the most appropriate passport sex.

Diagnostic algorithm for hypogonadism
Scheme - 1

Differential Diagnosis

Differential Diagnosisand rationale for additional research

Hypogonadism in a child should be distinguished from the constitutional form of delayed sexual development.

NB! With the established diagnosis of hypogonadism, it is necessary to clarify its form: primary, secondary, tertiary.

Differential diagnosis of hypogonadism in children

Form of hypogonadism	Damage level	Sex hormone levels	FSH and LH levels
Primary	Gonads	Low/Low-Normal	High/Normal
Secondary	Pituitary	Short	Low/Low-Normal
Tertiary	Hypothalamus	Short	Low/Low-Normal

NB! Interpretation of the results of the hormonal profile is carried out taking into account clinical picture and age of the patient

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Treatment

Drugs ( active substances) used in the treatment

Groups of drugs according to ATC used in the treatment

(G03BA03) Testosterone
(G03F) Progestogens in combination with estrogens
(G03C) Estrogens

Treatment (ambulatory)

TREATMENT TACTICS AT OUTPATIENT LEVEL
Treatment of hypogonadism in children aims to ensure the appearance of secondary sexual characteristics appropriate for the age and sex of the child.

Non-drug treatment:
mode: II;
professional psychological support child and parents, balanced diet, moderate physical activity, good sleep;
diet: table number 15.

Medical treatment
With constitutional form in the presence of social difficulties to induce the production of endogenous sex hormones in boys are used for 3-6 months, or anabolic steroid, or small doses of testosterone preparations, in girls - ethinylestradiol in small doses.

For primary hypogonadism replacement therapy with sex hormone preparations is indicated, taking into account the passport sex. It is advisable to prescribe it only when the child reaches the predicted growth (at the age of 15-17 years), since its earlier appointment is fraught with the formation of short stature due to the early closure of growth zones. At the same time, if there are difficulties of a psychosocial nature, as well as taking into account ethnic and family characteristics, earlier treatment is possible. On average, girls begin therapy at 12–13 years of age, and boys at 13.5–15 years of age (D).
Start substitution therapy with minimal doses of drugs.

Atboys prolonged forms of testosterone esters are used for parenteral administration. The initial dose is 50 mg once a month for 6-8 months with a gradual increase in dose by 50 mg once every 6-8 months (D). After reaching a dose of 250 mg 1 time in 3-4 weeks, it is possible to use prolonged forms of testosterone, which are administered 1 time in 3-4 months. The dose of the drug is selected individually under the control of the level of testosterone in the blood, which, against the background of ongoing therapy, should always be within normal indicators. Testosterone levels in the blood are monitored 3 weeks after the injection. If the level of testosterone in the blood is at lower border normal or below, the frequency of injections is increased to 250 mg once every 2 weeks (D).
NB! Boys with very small testis and anorchia for cosmetic and psychological reasons prosthetics should be recommended.

Treatment of secondary hypogonadismin boys carried out by the use of gonadotropins. Treatment tactics are determined by the relevance of the issue of fertility for the patient at the present time.
The following options for starting treatment with gonadotropins are proposed.
start with FSH preparations 75-150 U / m 1 time in 2-3 days for at least 6 months, followed by the addition of hCG 1000-3000 U 1 time in 3-4 days, for a long time.
Start with chorionic gonadotropin at 1000-3000 U 1 time in 3-4 days until the level of tetosterone reaches at least 12 nmol / l, then add FSH preparations at 75-150 U / m 1 time in 2-3 days. under the control of AMH and inhibin B levels, spermograms.
immediately begin with the combined appointment of FSH preparations at 75-150 IU / m 1 time in 2-3 days and chorionic gonadotropin at 1000-3000 IU once every 3-4 days, for a long time.

Atgirlswith any optionhypogonadism treatment begins with the appointment of estrogenic drugs. For these purposes, preparations of conjugated (D) and natural estrogens are used. Preparations of natural estrogens are prescribed in a starting dose of 0.3-0.5 mg / day. It is possible to use transdermal estrogens, produced in the form of gels, which are applied once a day to the skin of the lower part of the anterior abdominal wall. After 1-2 years of estrogen monotherapy, they switch to cyclic estrogen-progestogen replacement therapy. For this purpose, preparations containing natural estrogens are used (D).

With Shereshevsky-Turner syndrome detected in the neutral period, monotherapy with somatropin preparations is prescribed. In cases diagnosed after 8-10 years, taking into account the wishes of the parents and the patient, combination therapy can be prescribed, including somatropin preparations and preparations of female sex hormones.

With a hermaphroditic structure of the external genitalia it is necessary to make a choice of an appropriate passport sex before the child reaches the age of two, and surgical correction genitals according to the chosen gender. The question of choosing a sex should be decided collectively: a geneticist, a psychologist, a gynecologist, a urologist, a pediatrician, an endocrinologist.

With cryptorchidism the only treatment is to bring down the retained testicles at 6-12 months of age (no later) to avoid future infertility and testicular cancer (ESPE, 2014, American Association Urologists, 2004 and Swiss Association of Urologists, 2008). Treatment of hCG with cryptorchidism is not indicated.

List of main medicines (having a 100% cast chance)

medicinal group	international generic name LS	Mode of application	Level of Evidence
Testosterone preparations	Testosterone undecanoate	Inside and / m	A
Preparations of female sex hormones	Estrogens, combined estrogen-progestogen drugs	inside	A
Preparations of genetically engineered growth hormone	Somatropin	PC	A

List of additional medicines(less than 100% probability of application): symptomatic therapy - according to indications.

Surgical intervention: no.

Further management:
All children and adolescents with hypogonadism are monitored for:
Growth rate once every 6 months;
bone age once a year;
Development of secondary sexual characteristics according to Turner - every 3 months.

In adolescent boys with primary hypogonadism receiving testosterone preparations, it is necessary to control the following indicators:

Parameter

Timing

The lack of sex hormones is called hypogonadism. In men, this disease is associated with insufficient secretion of androgens, and in women - estrogens. With hypogonadism, the manifestations of the disease primarily relate to the sexual sphere and reproductive abilities. Also, the lack of sex hormones provokes changes in metabolism and functional disorders various organs and systems.

sex hormones

Sex steroids in adults are formed mainly in the gonads. In women, the source of estrogens is the ovaries, in men, the source of androgens is the testicles.

The activity of sex steroid synthesis is regulated by the central regions of the endocrine system. The pituitary gland secretes stimulatory gonadotropins.

These include:

FSH - follicle stimulating hormone;
LH is a luteinizing hormone.

Both hormones support normal work reproductive system in adults and contribute to its proper development in children.

Follicle-stimulating gonadotropin causes:

accelerates the maturation of eggs in women;
triggers spermatogenesis in men.

Luteinizing gonadotropin:

stimulates the synthesis of estrogens in the ovaries;
responsible for ovulation (release of a mature egg);
activates the production of testosterone in the testicles.

The activity of the pituitary gland is subject to the regulation of the hypothalamus. In this department of the endocrine system, releasing hormones are produced for LH and FSH. These substances increase the synthesis of gonadotropins.

The hypothalamus secretes:

luliberin;
folliberin.

The first of them stimulates mainly the synthesis of LH, the second - FSH.

Classification of hypogonadism

The lack of sex steroids in the body may be due to damage to the hypothalamus, pituitary gland, ovaries or testicles.

Depending on the level of damage, 3 forms of the disease are distinguished:

primary hypogonadism;
secondary hypogonadism;
tertiary hypogonadism.

The tertiary form of the disease is associated with damage to the hypothalamus. With such a pathology, they stop enough releasing hormones (luliberin and follyliberin) are produced.

Secondary hypogonadism is associated with dysfunction of the pituitary gland. At the same time, gonadotropins (LH and FSH) cease to be synthesized.

Primary hypogonadism is a disease associated with the pathology of the gonads. In this form, the testicles (ovaries) cannot respond to the stimulating effects of LH and FSH.

Another classification of androgen and estrogen deficiency:

hypogonadotropic hypogonadism;
hypergonadotropic hypogonadism;
normogonadotropic hypogonadism.

Normogonadotropic hypogonadism is observed in obesity, metabolic syndrome, hyperprolactinemia. According to laboratory diagnostics with this form of the disease, normal levels of LH and FSH, a decrease in estrogens or androgens are observed.

Hypergonadotropic hypogonadism develops when the testicles (ovaries) are affected. In this case, the pituitary and hypothalamus secrete increased amount hormones, trying to activate the synthesis of sex steroids. As a result, an increased concentration of gonadotropins and a low level of androgens (estrogens) are recorded in the analyzes.

Hypogonadotropic hypogonadism is manifested by a simultaneous drop in blood tests of the levels of gonadotropins and sex steroids. This form of the disease occurs when central departments endocrine system (pituitary and/or hypothalamus).

Thus, primary hypogonadism is hypergonadotropic, while secondary and tertiary hypogonadism is hypergonadotropic.

Primary and secondary hypogonadism can be congenital or acquired.

Etiology of hypogonadotropic hypogonadism

Secondary hypogonadism can develop for a variety of reasons.

Congenital forms are associated with:

Cullman's syndrome (hypogonadism and impaired sense of smell);
Prader-Willi syndrome (a genetic pathology that combines obesity, hypogonadism and low intelligence);
Laurence-Moon-Barde-Biedl syndrome (a genetic pathology that combines obesity, hypogonadism, pigmentary retinal degeneration and low intelligence);
Maddock's syndrome (loss of gonadotropic and adrenocorticotropic functions of the pituitary gland);
adiposogenital dystrophy (a combination of obesity and hypogonadism);
idiopathic hypogonadism (cause unknown).

Isolated idiopathic hypogonadism may be associated with adverse effects on the fetus at the time of prenatal development. An excess of chorionic gonadotropin in the mother's blood, dysfunction of the placenta, intoxication, and exposure to drugs can adversely affect the emerging pituitary and hypothalamus. Subsequently, this can lead to hypogonadotropic hypogonadism. Sometimes observed a sharp decline synthesis of only one of the hormones (LH or FSH).

Acquired secondary hypogonadism can be caused by:

severe stress;
lack of nutrition;
a tumor (malignant or benign);
encephalitis;
trauma;
surgery (for example, removal of a pituitary adenoma);
irradiation of the head and neck;
systemic connective tissue diseases;
vascular diseases of the brain.

Manifestations of the disease

Congenital hypogonadism provokes violations of the formation of the genital organs and the absence of puberty. In boys and girls, the disease manifests itself in different ways.

Congenital hypogonadotropic hypogonadism in men leads to:

underdevelopment of the genital organs;
lack of spermatogenesis;
eunuchoidism;
gynecomastia;
deposition of adipose tissue according to the female type;
lack of secondary sexual characteristics.

For girls:

the external genital organs are developed correctly;
secondary sexual characteristics do not develop;
observed primary amenorrhea and infertility.

In adults, the loss of secretion of LH and FSH can lead to a partial regression of secondary sexual characteristics and the formation of infertility.

Diagnosis of the disease

Secondary hypogonadism may be suspected in children and adults with characteristic reproductive disorders.

To confirm the diagnosis is carried out:

external examination;
Ultrasound of the testicles in men;
Ultrasound of the small pelvis in women;
blood test for LH and FSH;
analysis for releasing hormones (luliberin);
blood test for androgens or estrogens.

In men, sperm can be examined (with an assessment of the number and morphology of gametes). In women, egg maturation is monitored (for example, with ovulation tests).

Secondary hypogonadism is put if a low level of FSH, LH, androgens (estrogens) is detected.

Treatment of hypogonadism

Treatment is carried out by doctors of different specialties: pediatricians, endocrinologists, urologists, gynecologists, reproductologists.

In boys, treatment should begin as soon as the disease is diagnosed. In girls, hypogonadism is corrected from the age of 13–14 (after reaching a bone age of 11–11.5 years).

Hypogonadism in men is corrected with drugs with gonadotropic activity. Therapy with exogenous testosterone does not restore its own spermatogenesis and the synthesis of sex steroids.

The choice of a specific medication to protect against a form of deficiency. The most commonly used preparations of chorionic gonadotropin. This substance is effective in the treatment of LH deficiency or a combined decrease in two gonadotropins. Chorionic gonadotropin used for idiopathic secondary hypogonadism, Maddock and Cullman syndromes, adiposogenital dystrophy.

If the patient is dominated by FSH deficiency, then he is shown treatment with other drugs - menopausal gonadotropin, serum gonadotropin, pergonal, etc.

In women, treatment is carried out:

chorionic gonadotropin;
clomiphene;
menopausal gonadotropin;
pergonal;
estrogen and progesterone.

Clomiphene stimulates the synthesis of gonadotropins in the pituitary gland. Chorionic hormone, menopausal gonadotropin and pergonal replace LH and FSH. Estrogens and progesterone are used with caution. These hormones suppress the pituitary gland. But they successfully replace the natural hormones of the ovaries.

This disease occurs in about 1 out of 1000 boys. Most often, the disease is inherited through the male line.

The point is that in the testicles there are special sex glands that secrete testosterone. Under its influence, sperm synthesis, development, growth and formation of the reproductive system occur.

If for some reason the level of testosterone drops, then pathologies arise, including underdeveloped genital organs and the absence of secondary sexual characteristics (pubic hair, a high timbre of a female voice, a female figure, etc.).

Causes and consequences

Video: "Hypogonadism in boys"

Symptoms

Treatment should only be clinical setting under the supervision of experts. No traditional medicine or self-medication will help here.

This complex disease, which requires individual approach And complex therapy using the most modern techniques.

Prevention

At the moment, there are no specific methods for the prevention of hypogonadism. It is only necessary to monitor the state of puberty of boys, noticing deviations, and consult a doctor in time.

You also need to monitor nutrition so that the child's body does not lack nutrients, necessary for normal growth and development. Regular exercise or exercise will also be beneficial.

Forecast

In this case, the prognosis depends on the age and severity of the disease.

If the disease is detected in early stages, then, naturally, the chances of a cure will be many times greater than that of an almost adult boy.

You need to understand that sexual development occurs up to a certain age (up to 17-19 years), and if you do not have time by this time, then the boy may remain barren for the rest of his life. He may completely lose attraction to the opposite sex and become a eunuch.

This disease has heavy psychological consequences for a child. Underdeveloped genitals can cause a decrease in self-esteem and serve as a reason for other mental disorders.

It is difficult for boys with hypogonadism to adapt to society because of the inconsistency with generally accepted standards. Many patients suffer from depression and neurosis, which often leads to the development of suicidal tendencies. In this case, efficiency is important, since every day without treatment is a lost opportunity.

Conclusion

Hypogonadism in boys can begin at any age. You should carefully monitor the development of the child and regularly undergo preventive examinations see a doctor in order to diagnose this disease in time. If necessary, you should hand over everything necessary tests and research, even if the violations are minor.

Puberty - milestone in the life of any person that determines his future. It is important to know that hypogonadism leads to infertility, impotence and lack of sexual desire, that is, a boy can lose male libido from childhood, which will radically change his life, not for the better.

Andrologist, Urologist

Conducts examination and treatment of men with infertility. Engaged in the treatment, prevention and diagnosis of diseases such as urolithiasis, cystitis, pyelonephritis, chronic kidney failure etc.

Hypogonadism is a syndrome that occurs as a result of a deficiency of sex hormones in the body associated with functional insufficiency of the sex glands - gonads. Develop this pathology can be for both men and women. In some cases, the manifestations of the syndrome are found in childhood and adolescence. Pathology is accompanied not only by the underdevelopment of the genital organs, but also has an extremely negative effect on the state of vitality. important systems and organs, skeleton, protein-fat metabolism, etc.

What is a disease and what are its types

A decrease in the production of sex hormones in the body due to various circumstances can occur in both women and men, but the manifestations of the disease will differ significantly.

Endocrinologists distinguish between primary and secondary hypogonadism. The first variant of the disease is provoked by pathologies directly related to the state of the gonadal tissue - testicles in men and ovaries in women. In this case, the secret produced by the sex glands is not enough for the normal formation and functioning of the internal and external genital organs.

As for secondary hypogonadism, in this case, the development of the disease is associated either with structural pathologies of the pituitary gland that negatively affect its functions, or with a malfunction of the hypothalamus, which controls the work of the pituitary gland. Both forms of the disease can be either congenital or acquired.

The primary form of the disease, which manifests itself in childhood, draws attention to the development of mental infantilism in the child, and the secondary can lead to mental disorders.

In addition, endocrinologists distinguish the following types hypogonadism:

hypogonadotropic - develops as a result of disorders of the hypothalamic-pituitary system, manifested in a decrease in the production of gonadotropins - pituitary hormones, which results in a decrease in the secretion of androgens in the testicles in men and estrogen in the ovaries in women;
normogonadotropic - is the result of the same disorders as hypogonadotropic, but a decrease in the secretory activity of the testicles and ovaries occurs against the background of a normal amount of gonadotropins;
hypergonadotropic, accompanied by a lesion glandular tissue testicles and ovaries against the background of increased secretion of hormones by the pituitary gland.

Depending on the age at which hormonal deficiency developed, hypogonadism is divided into the following types:

embryonic (embryonic period);
pre-pubertal (from birth to 12 years, when active puberty begins);
post-pubertal (from 12 years old);
age (climacteric) in men and women, occurring due to a decrease in the production of sex hormones.

Causes of the development of pathology in children and adults

Congenital primary hypogonadism can be caused by the following reasons:

testicular aplasia (absence of one or both testicles in the scrotum);
underdevelopment of the testicles, accompanied by an increase mammary glands in men, the absence of spermatozoa and a decrease in testosterone secretion (Klinefelter's syndrome);
chromosome defects that cause short stature and failures in the development of the reproductive system (Shershevsky-Turner syndrome);
complete absence of sperm production, causing infertility, with other general norms (del Castillo syndrome);
lack of perception by the body of androgens (false male hermaphroditism).

Congenital secondary hypogonadism develops in the following cases:

damage to the hypothalamus;
low level of gonadotropins - Kallman's syndrome, which includes external deformities ("cleft lip", facial asymmetry, extra fingers, etc.), eunuchoidism, testicular underdevelopment;
dwarfism of the pituitary nature;
congenital brain tumors;
insufficiency of pituitary functions, resulting in infertility, underdevelopment of the genital organs, eunuchoidism (Maddock's syndrome).

Acquired primary hypogonadism occurs as a result of changes in the testicles and ovaries under the influence of external and internal factors that occurred after birth. Among these factors can be mentioned:

damage and neoplasms of the testicles and ovaries;
underdevelopment of the epithelium that forms surface layer ovaries and testicles, manifested by high growth, enlargement of the mammary glands (in men) and underdeveloped external genital organs;
functional insufficiency of the testicles and ovaries, which has developed due to medical procedures, such as radiation therapy, and surgical operations on the organs of the scrotum, ovaries, hernia repair, etc.

Acquired secondary hypogonadism can develop due to the following factors:

pituitary insufficiency, provoking the development of obesity;
pituitary-hypothalamus insufficiency, i.e. decreased production of gonadotropins and androgens (LMBB syndrome);
craniocerebral injuries and tumors of the pituitary-hypothalamus region, in particular, pituitary adenomas;
excess prolactin secreted by the pituitary gland (hyperprolactinemia syndrome).

In addition, the following factors can play the role of a catalyst in the development of hypogonadism:

impact on the body of toxic substances;
long-term use of antibacterial and steroid drugs;
alcohol abuse;
transferred infections.

Symptoms and signs

The symptomatic picture of hypogonadism in men is determined by the degree of androgen deficiency. With the development of pathology in embryonic period a child can be born a hermaphrodite, i.e. have both female and male sex organs at the same time. If the disease began to develop before the boy's puberty, his sexual development is inhibited and characteristic signs of eunuchoidism are formed - disproportionately high growth with weak bones, underdeveloped muscles, narrow chest, long arms and legs, squeaky voice. In other cases, on the contrary, the formation of the body according to the female type may occur, an increase in the mammary glands and obesity can be observed. The penis and prostate gland are underdeveloped, there is no growth of hair on the pubis and face, potency and libido are absent.

In cases where hypogonadism develops in the postpubertal period, its clinical manifestations are less pronounced. Moreover, with all types of diseases, there are always symptoms of a decrease in testicles in size, a decrease in erection, a decrease in sperm production, infertility and a lack of sexual desire. In addition, the patient complains about muscle weakness and rapid fatigue.

In women suffering from hypogonadism, the main symptoms can be considered:

violation of menstruation or their complete absence;
underdevelopment of the genital organs and mammary glands;
lack of hair or scanty pilosis of the pubis and armpits;
narrow flattened pelvis.

If the pathology developed in a girl after the onset puberty, her sexual characteristics undergo regression - the genitals gradually atrophy, and menstruation stops.

Not to mention obvious signs hypogonadism, such as hermaphroditism, in newborns, the evidence of the presence of pathology can be the fact that the testicles are in a position from which they cannot subsequently descend into the scrotum - for example, they can be prevented by a connective tissue barrier. Normally, the testicle is palpated either in the lower part of the inguinal canal, or in the region of the inguinal ring, and it can be easily manually lowered into the scrotum. In addition, the presence of pathology is evidenced by a deficiency of sex hormones.

Basic diagnostic methods

The main diagnostic task is to differentiate hypogonadism from hypothyroidism, thyrotoxicosis, Cushing's disease, and a number of others.

Diagnosis of hypogonadism, first of all, is carried out on the basis of the patient's complaints, analysis of his anthropometric indicators, including the genitals, as well as the correspondence of the level of puberty to the patient's age.

In addition, there is whole line laboratory and hardware research:

skeletal radiography - allows you to determine the stage of ossification of the growth zones of bones, on the basis of which a conclusion is made about the compliance of their condition biological age sick;
spermogram for men - analysis quality composition sperm, if it can be obtained, since in some cases this is not possible;
densitometry - definition mineral composition bones, which allows to identify deviations from the norm and, in particular, osteoporosis;
Ultrasound of the uterus for women - detection of underdevelopment (hypoplasia) of the uterus and ovaries;
MRI of the brain to determine the state of the hypothalamic-pituitary system;
blood and urine tests for hormone levels - in the presence of pathology, men have a testosterone deficiency and an excess of estradiol (with a tendency to feminization), and women have a decrease in estrogen levels and an increase in gonadotropins.

Treatment of pathology

There are no general therapeutic methods for the treatment of hypogonadism - the strategy is selected by the doctor purely individually and will depend on the type of disease, the nature of functional disorders, the age of the patient in whom the pathology was detected, etc.

It is important to know that the use of funds traditional medicine for the treatment of hypogonadism, at best, it is useless, and at worst, it is harmful, since the time necessary for the effective treatment of the pathology will be missed.

Conservative therapy

Congenital forms of the disease, as well as hypogonadism that developed before the onset of puberty, cannot be cured. Therapy in this case will consist in correcting the patient's condition with the help of lifelong hormone replacement, but infertility, as a rule, cannot be cured.

In secondary forms of hypogonadism, a stimulating drug therapy gonadotropins in combination with sex hormones - testosterone and estrogen. In addition to hormone replacement, the patient may be recommended drugs that suppress the synthesis of unwanted hormones. An example is Anastrozole, which inhibits (slows down) the synthesis of estrogen in the body.

IN drug therapy hypogonadism in women in addition to special hormonal drugs successfully used oral contraceptives, which include a combination of two types of hormones - estrogens and gestagens. After 45 years, patients are recommended to take Estradiol, Cyproterone and Norethisterone.

It is important to know that hormone replacement is contraindicated in cancers of the mammary glands and genital organs, with cardiovascular pathologies, kidney disease, liver failure etc.

In addition, the patient is also shown vitamin and immunotherapy, classes therapeutic gymnastics, swimming in the pool and physical activity. special recommendations regarding the diet, no, but the patient's diet should be balanced, it is especially important to limit the use of foods containing animal fats and light carbohydrates.

Surgery

Surgical treatments may be used to compensate for missing testicles. This happens either by the method of transplantation (transplantation) of an organ, or by implanting an artificial testicle for cosmetic purposes. Besides, surgically it is possible to bring down the testicle located in the abdominal cavity into the scrotum. Huge psychological damage to the patient causes underdevelopment of the penis, which can also be eliminated with the help of plastic surgery.

Similar surgical interventions are performed using microsurgery methods with subsequent mandatory control of the transplanted organ and the hormonal state of the patient. A complex approach in the use of surgical methods of therapy allows you to resume the development of the genital organs, restore potency and even in some cases cure infertility. Surgical methods are not used to treat female hypogonadism.

Prognosis and possible complications

Timely adequate hormone replacement can significantly affect the patient's condition. With the help of such therapy, it is possible to achieve penis growth in men and restore spermatogenesis, return menstrual cycle in women, normalization of the state of bone tissue, etc. Surgical methods help to eliminate not only cosmetic defects, but also to achieve the restoration of the functions of the organs of the reproductive system. As for the prevention of the disease, such, unfortunately, does not exist.

The negative consequences of the disease can be considered serious functional disorders which become significant obstacles in the process of a person’s adaptation in society, this is especially acute in the adolescent environment, where the awareness of one’s difference from peers causes moral suffering to the child. A patient with hypogonadism cannot build normal sexual relations with a partner, often deprived of the opportunity to have a family.

Elena Malysheva about male hypogonadism - video

If you notice signs in yourself or your child that may indicate the development of hypogonadism, you should immediately rush to the endocrinologist. Even in cases where the disease cannot be cured, the patient's condition can be fully compensated with the help of adequate therapy and improve his quality of life.