Dysfunction of the parathyroid glands. Thyroid gland and dysfunction

Primary hyperparathyroidism – pathology of the parathyroid glands themselves. Causes: autonomously functioning adenoma (or several adenomas, observed in 70–80% of cases of primary hyperparathyroidism), primary glandular hyperplasia (10–15% of patients with hyperparathyroidism), parathyroid carcinoma thyroid gland(less than 5% of cases).

Secondary hyperparathyroidism caused by prolonged hypocalcemia, usually in combination with hyperphosphatemia and the secondary development of hyperfunction and hyperplasia of the parathyroid glands.

Kidney pathology leading to hypocalcemia (most common reason). Chronic renal failure is accompanied by a decrease in phosphate excretion and the development of hyperphosphatemia. This leads to a decrease in the level of Ca2+ in the blood and stimulation of the function of the parathyroid glands. Tubulopathies and renal rickets.

Intestinal pathology. Malabsorption syndrome, accompanied by impaired absorption of calcium in the intestine. Steatorrhea - increased excretion of fat, fatty acids, their compounds, and associated calcium salts with feces. Pathology bone tissue. Osteomalacia is the softening of bones and their deformation due to a deficiency of calcium salts and phosphoric acid in them. Deforming osteodystrophy (Paget's disease). It is characterized by bone tissue resorption, calcium deficiency, and bone deformation. Hypovitaminosis D.

Tertiary hyperparathyroidism. Reason: long-term secondary hyperparathyroidism, which leads to the development of an adenoma (or adenomas), acquiring the property of autonomous functioning and hyperproduction of PTH. Under these conditions, the feedback between the level of CA2+ in the blood and the secretion of PTH is destroyed.

The main manifestations of hyperparathyroidism are shown in the diagram (P.F. Litvitsky, 2002).

Hypoparathyroid conditions(hypoparathyroidism, hypoparathyroidism, parathyroid insufficiency) are characterized by a decrease in blood levels and/or the severity of the effects of PTH in the body. There are glandular and extraglandular hypoparathyroidism (pseudohypoparathyroidism).

Primary (glandular) hypoparathyroidism is caused by the absence, damage or removal of the parathyroid glands. Extraglandular (peripheral) hypoparathyroidism is also called pseudohypoparathyroidism. Pseudohypoparathyroidism (eg, Albright's disease) is an inherited disease characterized by target organ resistance to PTH.

The main manifestations of hypoparateriosis are shown in the diagram (P.F. Litvitsky, 2002).

Chapter general pathophysiology of the nervous system

Pathophysiology nervous system studies the general patterns and basic mechanisms of development of pathological processes that underlie various nervous disorders that arise from various damage to the nervous system.

The general principles of the pathophysiology of the nervous system will be briefly discussed according to the concepts and ideas of the leading Russian school of pathophysiologists under the leadership of Academician of the Russian Academy of Medical Sciences, Professor G.N. Kryzhanovsky.

Mechanisms of development of pathological processes in the nervous system. Each pathological process in the nervous system begins with its damage, which is caused by the action of physical and chemical factors of various natures. These damages are expressed in various destructive and disintegrative phenomena, in disturbances of chemical processes.

But these phenomena in themselves are not mechanisms for the development of the pathological process; they represent a necessary condition and reason for the development of the pathological process. The development itself is carried out by other, endogenous mechanisms that arise secondarily after and as a result of damage. These endogenous mechanisms are inherent in the damaged and altered structures of the nervous system themselves. The emergence of endogenous mechanisms represents the stage of endogenization of the pathological process, without which the process cannot develop.

Thus, pathological processes in the nervous system, having arisen as a result of the action of a pathogenic agent, can further develop without additional exogenous pathogenic influences by endogenous mechanisms themselves. For example, degenerative processes in a neuron caused by ischemia or massive exposure to excitatory amino acids (glutamate) can continue and increase in intensity even after the cessation of ischemia, under conditions of reoxygenation, and lead to the death of the neuron (delayed neuron death).

However, one should not think that the continued action of the etiological factor is not important for the further development of the pathological process: on the contrary, it contributes to this development, causing new pathological changes, disrupting the mechanisms of protection and compensation and weakening the sanogenetic activity of antisystems.

Protective mechanisms of the NS and routes of entry of pathogenic agents into the NS. The entire central nervous system, in addition to the superficial membranes, has a specialized blood-neuronal or blood-brain barrier (BBB), which protects the brain and other parts of the central nervous system from the effects of pathogenic substances, toxins, viruses, microorganisms that may be in the blood. The role of the BBB (as you know from the physiology course) is performed by the brain vessels themselves, as well as glial elements (astrocytes). The BBB also does not allow biologically active substances to pass through, which can play the role of neurotransmitters and cause a neuronal response.

In fetuses and newborns, the BBB is not yet mature enough and is permeable to many substances.

Under pathological conditions (under the influence of pathogenic factors), the BBB can become permeable, which leads to the penetration of exogenous and pathogenic substances into the central nervous system. endogenous origin and the emergence in connection with this of new pathological processes and nervous disorders. Pathological permeability of the BBB occurs during convulsive conditions, acute arterial hypertension, ischemia and cerebral edema, under the action of antibodies to brain tissue, encephalitis, etc. Under severe stress, the BBB becomes permeable to the influenza virus.

The pathways for pathogenic agents to enter the central nervous system may primarily be through the nerves. The neural route of entry into the CNS is characteristic of tetanus toxin, polio viruses, rabies, etc. Having entered locally through any neural pathway or through a disrupted BBB, a pathogenic agent (toxin, virus) can further spread throughout the CNS transsynaptically with an axoplasmic current, involving different neurons into the pathological process. Antibodies to brain tissue and neurotransmitters can also spread through the NS with axoplasmic current, causing corresponding pathology.

You know that in addition to damaging ones, there are also various sanogenetic mechanisms that prevent the occurrence of pathological changes in the nervous system or stop these changes. The antisystem usually selectively prevents the development of the corresponding pathological system or suppresses its activity. They are activated by the action of a pathogenic agent or an already emerging pathological system (for example, the antinociceptive system, which secretes beta-endorphins and enkephalins, causing analgesia). Consequently, genetically determined or acquired deficiency of the antisystem is a predisposing factor and condition for the development of the pathological process.

Trace reactions in NS pathology. After each pathological process, structural and functional changes remain in the nervous system, which can remain in the form of traces hidden under normal conditions. These changes do not appear functionally not only due to their weakening, but also due to the mechanisms of compensation and tonic inhibitory control from the various structures The central nervous system and, in particular, from the antisystem side. Under the influence of new pathogenic agents that activate hidden changes and disrupt control mechanisms, these changes can functionally manifest themselves, which will be reflected in the appearance of certain symptoms. Such reactions are called trace reactions.

The more significant the hidden structural and functional changes and the less effective the control mechanisms, the easier the trace reactions are reproduced. Therefore, in the early stages of recovery, trace pathological effects can occur due to the action of many pathogenic agents, but in later stages they are reproduced more weakly.

Loss of NS functions. Damage to one or another formation of the NS entails disruption or loss of its function. Due to the high degree of reliability of the functioning of nerve formations and the activity of compensatory mechanisms, disruption and loss of function occurs, as a rule, not at the beginning of the pathological process, but when significant damage occurs. When a functional defect manifests itself clinically, this means that pathological changes have become so significant that the mechanisms of reliability and compensatory coverage of the defect are no longer sufficient. This means that the pathological process at this stage has already reached significant development, and does not begin, as is commonly thought.

The degree of dysfunction is determined not only by the number of damaged nerve elements. Around the area of damage in the spinal cord or in the brain, an inhibition zone appears, which, on the one hand, has a protective significance, but on the other, increases and intensifies the functional defect. This situation occurs, for example, with traumatic damage to the central nervous system, ischemic cerebral infarction, and with polio. The restoration of function does not occur due to the regeneration of neurons (they do not regenerate), but due to the normalization of reversibly damaged cells and a decrease in the inhibition of other neurons.

Weakening and even loss of function may not be due to organic damage to the nerve formation that performs this function, but to its deep inhibition. Thus, with hyperactivation of some parts of the reticular formation of the medulla oblongata, increased descending inhibition of spinal cord reflexes occurs. These types of pathology, for example, include hysterical paralysis associated with inhibition of locomotor centers, suggestive (suggestible) loss of function.

Disinhibition of neurons. Each neuron is under constant tonic inhibitory control, which prevents it from responding to numerous random impulses coming from various sources.

Inhibition deficiency can be primary due to direct damage to inhibitory mechanisms (due to the action of tetanus toxin, strychnine) or secondary, when excessive neuronal activity caused by depolarizing agents and other factors overcomes inhibitory control. The mechanisms of inhibitory control (remember physiology) are very sensitive to various pathogenic influences and unfavorable conditions for the activity of the nervous system. Therefore, deficiency of inhibition and disinhibition of neurons to one degree or another occur in almost all forms of NS pathology (they are typical pathological processes in the NS).

For example, a number of pathological reflexes that arise in humans under conditions of disturbance of supraspinal influences are the result of disinhibition of spinal centers. These include the Babinski reflex, grasping, sucking and other reflexes that were normal in the early periods of development and then suppressed by developing controlling descending influences.

Denervation syndrome. Denervation syndrome is a complex of changes that occur in postsynaptic neurons, organs and tissues due to the cessation of nervous influences on these structures.

In muscle, denervation syndrome is manifested by the disappearance of the end plate on the muscle fiber, where the entire cholinergic apparatus is concentrated, and the appearance instead of acetylcholine receptors along the entire length of the muscle fiber, and therefore the sensitivity of the fiber to acetylcholine increases. The result is fibrillary twitching of the denervated muscle. This is a reflection of the reaction of muscle fibers to acetylcholine supplied to them from various sources. The absence of the end plate and the presence of multiple receptors on the muscle fiber are phenomena that occur in the early stages of development of the neuromuscular system. In addition, a spectrum of embryonic-type enzymes appears in denervated muscle.

Thus, during denervation there is a kind of return muscle tissue to embryonic stages of development. This effect is the result of the loss of the controlling, trophic influences of the nerve, as a result of which the genetic apparatus of the muscle fibers is disinhibited. When the muscle is reinnervated, nervous control is restored and these phenomena disappear.

A general pattern of denervation syndrome is an increase in the sensitivity of denervated structures not only to mediators, but also to other biologically active substances, as well as to pharmacological agents. Denervation can occur not only after a nerve break, but also in many forms of pathology, under the influence of pharmacological agents that disrupt nerve influences and blockade of neuroreceptors. Therefore, denervation belongs to the category of typical pathological processes in the nervous system.

Deafferentation. An impulse entering a neuron from any source is an afferent impulse for the neuron. Turning off this afferentation represents deafferentation of the neuron. Complete deafferentation of the neuron does not occur, since the neurons of the central nervous system have a huge number of inputs through which impulses come from various sources. However, even with partial deafferentation, an increase in neuron excitability and a disruption of inhibitory mechanisms occur. Partial deafferentation of neurons can occur in various diseases of the nervous system and is another typical pathological process.

The phenomenon of deafferentation often refers to syndromes associated with loss of sensitivity due to lack of stimulation from the periphery. Under these conditions, changes in movements may also be observed in the form of a violation of their accuracy.

Spinal shock. Spinal shock occurs as a result of a rupture of the spinal cord and represents a deep but reversible inhibition (loss) of motor and autonomic reflexes occurring below the break. Suppression of reflexes is associated with the lack of activating influences from the brain. In humans, spinal shock lasts several months (in frogs it lasts several minutes). When function is restored in a person after complete paraplegia, flexion reflexes first appear, having a pathological (Babinsky) character, then generalized reflexes and movements such as spinal automatisms; in the chronic stage, extensor reflexes arise, which sometimes turn into extensor spasms. All these phenomena arise due to disinhibition of the spinal locomotor (motor) apparatus.

Similar stages - depression and hyperactivation - are also characteristic of changes in autonomic reflexes that occur below the spinal cord break.

Disorders of nervous trophism of tissues and organs. Nerve trophism refers to the trophic influences of a neuron, which ensure the normal functioning of the structures it innervates - other neurons and tissues.

The neuron and the structure innervated by it form a regional trophic circuit in which there is a constant mutual exchange of trophic factors called trophogens, or trophins. Damage to this trophic circuit in the form of disruption or blockade of the axoplasmic current flowing in both directions, transporting trophic factors, leads to the emergence of a dystrophic process not only in the innervated structure (muscle, skin, other neurons), but also in the innervating neuron. Magendie was the first to show (1824) that cutting a branch of the trigeminal nerve in a rabbit causes ulcerative keratitis.

Dystrophic disorders (ulcers) arise due to a deficiency in denervated tissues of trophic factors that control the genetic apparatus. This means that the activity of the genome of denervated structures is disrupted, as a result of which protein synthesis is disrupted and collapsing intracellular structures are not replenished. Along with this, normally suppressed genes are disinhibited, and new proteins appear.

Trophic factors include various kinds of proteins that promote the growth, differentiation and survival of neurons (nerve growth factor, fibroblast growth factor, etc.). Axon growth occurs with the obligatory participation of trophic factors, their synthesis increases with injuries of nervous tissue.

In many diseases of the nervous system, especially in the so-called diseases of old age, there is a decrease in the content of trophic factors.

Along with the deficiency of normalizing trophic factors, pathogenic trophic factors (pathotrophogens) that arise in pathologically altered cells and induce pathological conditions can play an important role in the pathogenesis of NS lesions. For example, substances may appear in epileptic neurons that, entering with an axoplasmic current into other neurons, induce epileptic properties in them. Pathological proteins - degenerins - take part in the mechanisms of apoptosis (programmed death) of neurons. The role of a pathotrophogen is apparently played by beta-amyloid, which is found in large quantities in the brain tissue of Alzheimer's disease.

In addition to the local dystrophic process caused by changes in the regional trophic circuit, a generalized dystrophic process may occur. It manifests itself in the form of gum damage, hemorrhages in the lungs, ulcerations and hemorrhages in the stomach and intestines. Such similar changes can occur in various chronic nerve injuries, which is why they are called the standard form of nervous dystrophy.

Trophic factors spread from neuron to neuron transsynaptically.

Thyroid dysfunction, the symptoms of which cannot always be recognized correctly, is very dangerous for the human body. The thyroid gland, shaped like the wings of a butterfly, as if enveloping the larynx, is a small internal secretion organ weighing only 20 g. It bears a huge load, being fully responsible for the mental, mental, physical development and health of a person. Any, even the most minor, malfunction of this organ can lead to serious illnesses.

Thyroid hormones and their functions

The thyroid gland is one of many organs endocrine system the human body is responsible for the biological processes occurring in it.

Its function is the production of two types of hormones:

T-4 (thyroxine) and T-3 (triiodothyronine) are hormones responsible for the content and production of iodine;
calcitonin, thyrocalcitonin - hormones on which the calcium content in the body and how it is absorbed depend.

Increased productivity or increased production of iodine-containing hormones - hyperthyroidism, decreased functional activity - hypothyroidism.

Causes of thyroid dysfunction

The human body is constantly exposed to various external factors, influencing the activity of the endocrine glands, including the thyroid gland:

disturbed ecology;
increased levels of radiation;
deficiency or excess of vitamins;
chronic inflammatory and infectious diseases;
disease of the thyroid gland itself;
brain disease and injury;
congenital malformation or complete absence glands;
laryngeal injury;
hereditary genetic disorders;
stressful situations;
mental stress;
eating disorders;
improper use of medications;
taking hormonal medications without medical supervision;
iodine deficiency in the body.

All these factors can lead to malfunction of the thyroid gland and cause hormonal disorders and, as a result, serious diseases caused by metabolic disorders in the human body. Women are more susceptible to diseases associated with dysfunction of the thyroid gland. They are more susceptible to stressful situations, pay less attention to themselves when any inflammatory diseases, but experience great physical and mental stress.

Pregnancy is a special period in a woman’s life when all the functions of her body are weakened. This time is associated with restructuring throughout the body, so anemia, iodine and calcium deficiency may occur. The thyroid gland bears during this period increased load and does not always cope with it.

The period of formation and growing up is no less dangerous from the point of view of thyroid dysfunction. Hormonal changes, puberty - this is the time when you should reverse Special attention on the work of all endocrine glands, especially on the work of the thyroid gland. As girls get older and grow up, they are faced with the problem of contraception and sometimes start taking it without prescriptions or recommendations from a doctor. contraception, many of which are hormonal drugs. This can cause a malfunction of the thyroid gland and lead to irreparable consequences.

Of course, older people are also at risk.

IN mature age Disturbances in the activity of the endocrine glands are not immediately noticed.

All diseases bad feeling attributed to the age factor. Often, due to such inattention to oneself and one’s health, time is lost when one can still help and cure the patient. And in this situation, women are at greater risk of the disease. Menopause is also a hormonal change and stress for the whole body. At such times, you need to pay as much attention as possible to your body.

Symptoms of thyroid dysfunction

What should you pay attention to first?

All disturbances in the functioning of the thyroid gland are associated with changes in the amount of hormones it produces.

The condition caused by decreased production is called hypothyroidism.

Associated with him serious violations activity of the heart and blood vessels, sexual activity, mental health. Some external and internal signs will tell you when to see a doctor:

Hypothermia. A condition in which a person is constantly cold. The patient feels uncomfortable and chilly even in the summer heat. Constantly cold extremities begin to bother the patient at the very beginning of the disease, then the overall body temperature decreases, and this condition becomes habitual.
A pronounced apathy appears - indifference and indifference to everything that happens around. The patient doesn't want anything. The state of depression is sometimes replaced by causeless tears. Can lead to nervous disorder or even a nervous breakdown. A person may fall into depression, from which it is very difficult to get out without the help of a doctor.
Another manifestation of the disease is increased excitability, irritability and even anger, which is dangerous because it can result not only in a nervous breakdown, but also in a general disorder of mental health. In women, PMS is pronounced, sometimes turning into a state of hysteria.
Constant desire to sleep. The patient complains of a feeling of lack of sleep, despite the fact that the time allotted for sleep is at least 7 hours.
Fast fatiguability. Rest, regardless of the type of activity, is required approximately every 2-3 hours.
Weakness, tremors of the limbs, feelings of anxiety and inexplicable, unjustified fear. Changes in the patient’s behavior become noticeable to others. Something worries him all the time.
Swelling of the extremities, especially the hands, appears. At the slightest load, the hands begin to tremble, then go numb. Usually, the cause of such sensations is considered to be cervical osteochondrosis and there is no rush to see an endocrinologist.
In women, they manifest themselves with particular force periodic pain, accompanying menstruation. Often, patients consult a gynecologist with suspected inflammation of the appendages. An experienced doctor will definitely refer the patient to a gynecologist-endocrinologist.
Changes in the condition of the skin become visible. The skin is dry, flaky and itchy.
Dizziness, nausea, weakness, increased sweating. Sweat acquires a sharp, unpleasant odor.
Disturbances in the functioning of the heart are manifested by the occurrence of tachycardia or bradycardia. Shortness of breath appears. Similar condition often attributed to diseases such as angina pectoris and cardiovascular failure. They turn to a cardiologist for help, but even here the specialist will immediately understand what the reasons are and refer the patient to an appointment with an endocrinologist.
Hyper- or hypotension occurs. Changes blood pressure will lead to severe headaches, nausea and dizziness.
Pain in the joints and muscles may occur not only during exercise, walking, or any movement, but also at rest. This is due to vascular changes.
Violated general exchange substances in the body. The color of the skin changes, the activity of the gastrointestinal tract is disrupted, and quite long-term constipation is possible.
Sometimes the patient is worried not just about a lack of appetite in the morning, but about a complete aversion to food in the morning. But in the evening, before bed, and sometimes even in the middle of the night, an irresistible feeling of hunger arises.
Allergic reactions to food or medications may occur.
Sometimes metabolic disorders cause alopecia in patients. Hair becomes fragile, brittle, and falls out.
Disturbance in the activity of the sebaceous glands leads to the fact that the skin on the elbows and heels becomes rough, cracks and deep, poorly healing wounds appear, which prevent the patient from moving. On the contrary, pimples or acne appear on the skin of the face and back.
Nails peel, become thin, break, crack.
Body weight changes, shortness of breath appears.
Swelling, puffiness of the face, impaired functioning of facial muscles, slow speech.
An increase in cholesterol levels in the blood causes an increase in the size of the liver, the appearance of jaundice, and bitterness in the tongue.
In men, hypothyroidism leads to impotence, and in women, menopause occurs much earlier than expected.

Despite the variety of manifestations of disorders of the endocrine system, dysfunction of the endocrine glands develops in only four ways:

1. Direct damage to endocrine gland tissue by a pathogenic agent.

The most common factor that directly damages the endocrine glands is vascular disorders. For example, a change in the intensity of hormone secretion by the anterior pituitary gland often occurs with prolonged spasm of the vessels supplying this gland. Diabetes mellitus often develops as a result of atherosclerotic changes in the pancreas arteries. Thrombosis of the adrenal arteries or hemorrhages into their tissue lead to manifestations of varying degrees of severity of their insufficiency, etc.

Functional disorders endocrine glands may be caused infectious agent(For example, thyroiditis- inflammation of the thyroid gland of an infectious nature; diabetes as a result of infection of the body Coxsackie virus and etc.).

An important factor damaging these glands is tumors. Some tumors have a destructive effect on the tissue of the glands, which leads to their hypofunction. Others, having a glandular structure characteristic of a given gland (adenomas), are hormone-producing and have high, often uncontrolled, endocrine activity and thereby sharply increase the content of this hormone in the blood. Such tumors include, for example, insulinoma, which produces insulin and causes the patient to periodically experience a state of hypoglycemic coma. A hormone-producing tumor is pheochromocytoma- a neoplasm of chromaffin tissue that periodically releases into the bloodstream huge quantities adrenaline, causing hypertensive crises with the highest levels of blood pressure.

Inflammatory processes that affect the endocrine glands inhibit their function and can cause serious hormonal dysfunctions, as happens, for example, when inflammation of the ovaries.

Factors of direct damage to the tissue of the endocrine glands include their mechanical injuries.

2. A very common factor in the development of endocrine disorders is violation normal influence endocrine glands on top of each other, which can be both direct and indirect - through the inclusion of intermediate mechanisms.

The first type of such disorders includes endocrine dysfunction caused by changes in regulatory influence hypothalamic-pituitary system. As is known, the pituitary gland secretes a number of hormones that stimulate the activity of other endocrine glands, in particular the thyroid gland, adrenal glands, and gonads. At the same time, the activity of the pituitary gland is closely dependent on the production of releasing factors, causing increased production of these hormones by the pituitary gland. Thus, the hypothalamic-pituitary system is a regulator of the activity of the entire endocrine system, and a violation of this regulation will inevitably entail a change in the activity of other endocrine glands.

The second type of disorders that arise along this path is that, for example, strengthening the function of one of the endocrine glands causes changes in the body that initiate a restructuring of the activity of another endocrine gland, which can further lead to a disorder of its function. A typical example in this regard is the emergence diabetes mellitus with overproduction of the anterior pituitary gland somatotropin. The latter is an inhibitor hexokinase- a key enzyme in the carbohydrate metabolism process, under the influence of which glucose phosphorylation occurs. This enzyme is activated insulin. When hexokinase activity is suppressed by somatotropin, compensatory hyperfunction of β-cells occurs. Langerhans islets of the pancreas, during which the pancreas insular apparatus is depleted, which leads to the development of absolute secondary diabetes mellitus.

3. Third way - neurogenic. The activity of the endocrine glands, as well as other organs, is under the control of the regulatory centers of the nervous system. Violations of this regulation, as well as the occurrence of pathological conditions in various parts of the central nervous system, can also cause a disorder in the activity of the endocrine glands. For example, it is believed that approximately 80% of patients Graves' disease the cause of the disease is mental trauma or long-term neurotic state. Chronic nervous tension plays an extremely important role in the development diabetes mellitus etc. These neurogenic influences are mainly realized through changes in the intensity of secretion releasing factors hypothalamus.

4. The fourth way of disorders of the endocrine glands is associated with hereditary factor.

As already indicated in the chapter on etiology and pathogenesis diabetes mellitus, In the occurrence of this disease, the hereditary factor plays an extremely important role. At chromosomal diseases (Klinefelter, Shereshevsky-Turner syndromes, associated with pathology of sex chromosomes) hypofunction of the adrenal glands and gonads, development of the body according to the intersex type, etc. are noted.

These are the general ways of developing disorders of the endocrine system.

1. Tumors are a common cause of gland damage and hormone production disorders. If the tumor originates from secretory cells, excess amounts of hormones are usually produced, resulting in a picture of hyperfunction of the gland. If the tumor does not secrete the hormone, but only compresses and causes atrophy or destroys the tissue of the gland, its progressive hypofunction develops. Tumors of the glands can also produce hormones that are unusual for a given endocrine gland.

2. Endocrinopathies can be caused by congenital defects in the development of glands or their atrophy. The latter can be caused by a sclerotic process, chronic inflammation, age-related involution, long-term treatment with exogenous hormones, or a hormonally active tumor of the paired gland. Damage and atrophy of the gland may be based on autoimmune processes (diseases of the adrenal glands, thyroid gland, etc.). At the same time, autoimmune processes can also cause overproduction of hormones (by the thyroid gland).

3. Another common cause of damage to the peripheral endocrine glands is infection. Some of them (tuberculosis, syphilis) can be localized in various glands, causing their gradual destruction. In other cases, there is some selectivity of the lesion (viral mumps often causes orchitis and testicular atrophy).

4. The formation of hormones may be impaired due to hereditary defects in the enzymes necessary for their synthesis, or inactivation (blockade) of these enzymes. In this way, some forms of corticogenital syndrome, endemic cretinism, etc. arise. The formation of abnormal forms of hormones in the gland (with altered conformation, changes in the active center) is also possible. Such hormones have inferior activity or lack it altogether. In some cases, the intraglandular conversion of prohormone into hormone is disrupted (hence, its inactive forms are released into the blood). The cause of disturbances in the biosynthesis of hormones can be a deficiency of specific substrates included in their composition (for example, iodine). And finally, the cause of endocrinopathy may be depletion of hormone biosynthesis as a result of prolonged stimulation of the glands and its hyperfunction. In this way, some forms of insufficiency of beta cells of the islet apparatus of the pancreas arise, stimulated by long-term hyperglycemia.

Extraglandular forms of endocrine disorders. Even with completely normal function of the peripheral glands, endocrinopathies can occur. Let's consider the reasons for their occurrence.

1. When the ability of plasma proteins to bind hormones is weakened or excessively increased, the fractions of free, active hormone, and therefore the effects in “target cells,” may change (inadequately to the needs). Such phenomena have been established in relation to insulin, cortisol, and thyroid hormones. The cause of insufficient binding of hormones may be pathology of the liver, where the synthesis of the main plasma proteins occurs, including those that interact with hormones.

2. Inactivation of circulating hormones. This is usually due to the formation of antibodies to hormones. This possibility has been established in relation to exo- and endogenous hormones (insulin, ACTH, growth hormone).

3. Violations of hormone reception in target cells (on their surface or inside the cell). Such phenomena may be a consequence of the genetically determined absence or small number of receptors, defects in their structure, various cell damage, competitive blockade of receptors by “antihormones”, etc. Great importance is currently attached to antireceptor antibodies. Antibodies can be directed to various parts receptor and can cause various kinds of disorders: block the mechanism of “recognition” of the hormone and create a picture of hormonal insufficiency; bind to the active center of the receptor and imitate the hyperfunction of the gland, while inhibiting the formation of the natural hormone; lead to the formation of receptor-antibody complexes that activate factors of the complement system and lead to damage to the receptor. The formation of antibodies may be caused by a viral infection; it is believed that the virus can bind to a hormonal receptor on the cell surface and provoke the formation of antireceptor antibodies.

4. One form of insufficiency of hormonal effects may be associated with a violation of the permissive “mediating” action of hormones. Thus, the lack of cortisol, which has a powerful and versatile permissive effect on catecholamines, sharply weakens the glycogenolytic and lipolytic effects of adrenaline, the pressor effect and other effects of catecholamines. Another example - in the absence required quantities thyroid hormones cannot act normally growth hormone.

Endocrinopathies can be caused by disturbances in hormone metabolism. A significant part of hormones is destroyed in the liver, and with its lesions (hepatitis, cirrhosis), signs of endocrine disorders are often observed. Thus, a slowdown in cortisol metabolism, along with some manifestations of hypercortisolism, can inhibit the production of ACTH and lead to adrenal atrophy. Insufficient inactivation of estradiol inhibits the secretion of gonadotropins and causes sexual disorders in men. It is believed that excessive activation of enzymes involved in hormone metabolism is also possible. For example, if insulinase activity is excessive, relative insulin deficiency may occur.

Summarizing all that has been said, we can note the following. The causes and mechanisms of endocrine disorders are very diverse. Moreover, these disorders are not always based on insufficient or excessive production of the corresponding hormones, but always on the inadequacy of their peripheral effects in target cells, leading to a complex interweaving of metabolic, structural and physiological disorders.

We will outline in general outline causes and mechanisms of disorders of the so-called “classical” endocrine system.

APUD system in normal and pathological conditions

In 1968, the English pathologist and histochemist E. Pierce substantiated the theory of the existence in the body of a specialized highly organized neuroendocrine system. cellular system, the main specific property of which is the ability of its constituent cells to produce biogenic amines and polypeptide hormones (APUD system). The cells included in the APUD system are called apudocytes. The name of the system is an abbreviation of English words (amin - amines; precursor - predecessor; uptake - accumulation; decarboxilation - decarboxylation), indicating one of the main properties of apudocytes: the ability to form biogenic amines by decarboxylation of their accumulated precursors. Based on the nature of their functions, the biologically active substances of the system are divided into two groups: 1) compounds that perform strictly defined specific functions (insulin, glucagon, ACTH, growth hormone, melatonin, etc.) and 2) compounds with diverse functions (serotonin, catecholamines, etc.) . These substances are produced in almost all organs. Apudocytes act at the tissue level as regulators of homeostasis and control metabolic processes. Consequently, with pathology (the appearance of apudoms in certain organs), symptoms develop endocrine disease, corresponding to the profile of secreted hormones.

The activity of the APUD system, localized in the tissues of the lungs and gastrointestinal tract (stomach, intestines and pancreas), has now been most fully studied.

Apudocytes in the lungs are represented by Feyter and Kulchitsky cells. They are more developed in the lungs of fetuses and newborns than in the lungs of adults. These cells are located singly or in groups in the epithelium of the bronchi and bronchioles and have abundant innervation. Many specific endocrine cells of the lungs are similar to those in the pituitary gland, duodenum, pancreas and thyroid glands. Among the neuropeptides synthesized by the lungs, the following were found: leu-enkephalin, calcitonin, vasointestinal polypeptide, substance P, etc. The most numerous and well-organized group of apudocytes in the gastrointestinal tract are also Kulchitsky cells (Ec-cells). Their function is considered to be the synthesis and accumulation of biogenic amines - serotonin and melatonin, as well as peptide hormones - motilin, substance P and catecholamines. In addition, more than 20 types of cells (A, D, G, K, etc.) that synthesize polypeptide hormones have been found in the gastrointestinal tract. Among them are insulin, glucagon, somatostatin, gastrin, substance P, cholecystokinin, motilin, etc.

Types of apudopathies. Disorders of the structure and functions of apudocytes, expressed clinical syndromes, are called apudopathies. Based on their origin, apudopathies are distinguished between primary (hereditarily determined) and secondary (acquired) apudopathies.

Primary apudopathies include, in particular, multiple endocrine tumor syndrome (METS) various types(see table according to N.T. Starkova). This is an autosomal dominant disease characterized by multiple benign or malignant tumors arising from apudocytes of various locations. Thus, the group of diseases belonging to type I SMES includes patients primarily with the familial form of hyperparathyroidism. In this syndrome, hyperplasia of all parathyroid glands is detected in combination with a tumor of the pancreas and (or) pituitary gland, which can secrete excess gastrin, insulin, glucagon, VIP, PRL, STH, ACTH, causing the development of corresponding clinical manifestations. Multiple lipomas and carcinomas can be combined with type I SMES. Hyperparathyroidism is the most expressed endocrinopathy in type I SMES, and it is observed in more than 95% of patients. Gastrinomas (37%) and VIPomas (5%) are less common.

Type IIa SMEO is characterized by the presence in patients of medullary thyroid cancer, pheochromocytoma and hyperplasia or tumor of the parathyroid gland. The combination of medullary thyroid cancer with pheochromocytoma was first described in detail by Sipple (1961), therefore this variant of SMES is called Sipple's syndrome.

Secondary apudopathies can occur with diseases of the cardiovascular or nervous system, infectious diseases, intoxications, tumors localized outside the APUD system.

Based on their prevalence, a distinction is made between multiple apudopathies (characterized by the involvement of different types of apudocytes in the pathological process) and solitary apudopathies (the function of any one type of apudocyte is impaired). An example of one of the forms of multiple apudopathies can be the MEO syndrome described above. Among the solitary ones, the most common are apudom tumors, which originate from the cells of the APUD system and have hormonal activity. Although such tumors can sometimes produce several hormones originating from different types of cells, the clinical manifestations of solitary apudopathies are usually determined by the action of one hormone. Apudopathies are also distinguished according to their functional characteristics. There are hyper-, hypo- and dysfunctional forms of disorders. The basis of the first two forms is usually hyper- or hypoplasia of apudocytes, respectively; dysfunctional disorders are characteristic of multiple apudopathies. Below will be given a brief description of only some peptide hormones of the APUD system and their role in pathology.

Gastrin. This peptide is produced by G cells primarily in the pylorus of the stomach. Another representative of the APUD system has also been identified - bombesin, produced by P cells, which is a stimulator of gastrin release. Therefore, bombesin is called gastrin releasing hormone. Gastrin is a strong stimulator of hydrochloric acid secretion, and the latter inhibits its formation via negative feedback. In addition, gastrin stimulates the production of pancreatic enzymes and enhances the secretion of pancreatic juice and increases bile secretion; slows down in small intestine absorption of glucose, sodium and water, along with increased excretion of potassium; stimulates motor activity of the gastrointestinal tract.

In 1955, Zollinger and Ellison first described patients with recurrent peptic ulcers, severe hypersecretion of hydrochloric acid and an islet cell tumor - gastrinoma, producing an increased amount of gastrin. This triad of symptoms is called Zollinger-Ellison syndrome. Gastrinoma is most often localized in the pancreas, as well as in the submucosa of the duodenum. Up to 75% of pancreatic and up to 50% of duodenal gastrinomas give metastases. Clinically, the syndrome is manifested by rapidly developing ulcerative lesions (usually in the duodenal bulb), epigastric pain, frequent ulcerative bleeding, nausea, vomiting, and diarrhea.

Glucagon. A peptide hormone produced by the alpha cells of the pancreatic islets. Glucagon with a slightly higher molecular weight is secreted by the cells of the duodenal mucosa. Pancreatic glucagon has a pronounced hyperglycemic effect due to a sharp increase in glycogenolysis in the liver under its influence. Enteral hormone has a stimulating effect on insulin secretion. Thus, glucagon takes part in stabilizing blood glucose levels. When the blood glucose level decreases, glucagon is released. In addition, it is a lipolytic hormone that mobilizes fatty acids from adipose tissue.

More than 100 glucagenomas have been described - malignant hormonally active tumors localized mainly in the tail of the pancreas. Glucagenoma leads to the development of diabetic dermatitis syndrome. It is characterized by signs of moderate diabetes mellitus (due to hyperglucagonemia) and skin changes in the form of migratory necrolytic erythema. Glossitis, stomatitis, anemia, and weight loss also develop. Children often have convulsions, periods of apnea, and sometimes a coma.

Another hormone of the APUD system is somatostatin(or somatotropin-releasing). This inhibitory hormone is produced not only in the central nervous system (in the hypothalamus), but also in the D-cells of the stomach, intestines and pancreas, as well as in small quantities in all tissues of the body. In addition to the main physiological role- inhibition of the release of somatotropic hormone, somatostatin inhibits the release of insulin, thyroxine, corticosterone, testosterone, prolactin, glucagon, as well as gastrin, cholecystokinin, pepsin, etc. Along with the listed effects, somatostatin inhibits the motor activity of the gastrointestinal tract, has sedative effect, has the ability to bind to opiate receptors in the brain, affecting involuntary movements. From the above it follows that this hormone plays a very important role in the life of the body.

Clinical manifestations of hypersomatostatinemia (with pancreatic tumors that secrete this hormone - somatostatinomas) are very polymorphic. These are various combinations of diabetes mellitus, cholelithiasis, exocrine pancreatic insufficiency, gastric hypo- and achlorhydria, iron deficiency anemia, etc.

Vasoactive intestinal polypeptide(VIP). This peptide was first isolated from the small intestine, then found in the nerve formations of the entire gastrointestinal tract, as well as in the central nervous system, lungs and other organs. VIP inhibits gastric secretion, activates the secretion of intestinal juice, as well as the secretion of water and bicarbonate by the pancreas, causes relaxation of the lower esophageal sphincter and colon. In addition, VIP is capable of causing vasodilation, expansion of bronchioles, and stimulating the release of hormones from the pancreas and anterior pituitary gland; activate glucogenesis and glycogenolysis. An increase in the formation of VIP is most often observed with VIPoma - an endocrine tumor of the islet apparatus of the pancreas. This tumor leads to the development of Wermer-Morrison syndrome, manifested by diarrhea, steatorrhea, dehydration, weight loss, hypo- and achlorhydria. Hypokalemia, hypercalcemia, acidosis, and hyperglycemia develop. Convulsions and arterial hypotension may occur. Excessive formation of VIP is the main cause of profuse diarrhea in Werner-Morrison syndrome (endocrine cholera).

And finally, we will characterize another peptide of the APUD system. This substance-R. It is widely distributed in the central nervous system, especially in the hypothalamus, spinal cord, and lungs. In the gastrointestinal tract, substance P is found in the Meissner and Auerbach plexuses, in the circulatory and longitudinal muscles of the intestine. In the central nervous system, this peptide plays the role of a typical neurotransmitter; it is able to accelerate the metabolism of biogenic amines in the brain and modulate the pain response. At the gastrointestinal tract level, it has been established that substance P enhances secretion, but inhibits the absorption of electrolytes and water in the small intestine and causes contraction of the smooth muscles of internal organs.

To conclude the discussion of the topic, I would like to emphasize the following: 1) the presented material indicates that a very complex structural organization of neuroendocrine regulation of life activity has developed in the body during phylogenesis and a very wide range of possible causes and mechanisms for the development of endocrine disorders; 2) it can be noted that for last years Our understanding of the etiopathogenesis of endocrinopathies has expanded and deepened significantly. The subject of study was not only the “classical” pathology of the endocrine system, but also its “non-classical” types.

Chapter 31
ENDOCRINOPATHIES CAUSED BY DISTRIBUTION OF THE FUNCTIONS OF THE PITUITARY AND ADRENAL GLANDS

Pituitary gland dysfunction

Pituitary(cerebral appendage, pituitary gland) - an endocrine gland located at the base of the brain in the pituitary fossa of the sella turcica of the sphenoid bone of the skull and associated with the hypothalamic infundibulum diencephalon. The pituitary gland consists of two lobes. The anterior lobe, or adenohypophysis, is epithelial in nature. The posterior lobe of the pituitary gland, or neurohypophysis, is like an outgrowth of the brain and consists of modified neuroglial cells.

Hormones of the adenohypophysis:

1. Follitropin(follicle stimulating hormone, FSH). Activates the growth of ovarian follicles in women and the process of spermatogenesis in men.

2. Lutropin(luteinizing hormone, LH). In women, it helps complete the maturation of eggs, the process of ovulation and the formation of the corpus luteum in the ovaries, and in men it promotes cell differentiation interstitial tissue testicles and stimulates the production of androgens (testosterone).

3. Prolactin(luteomammotropic hormone, PRL). Activates the function of the corpus luteum, stimulates milk formation and promotes lactation (provided higher level estrogen).

4. Corticotropin(adrenocorticotropic hormone, ACTH). Stimulates the proliferation of cells of the adrenal cortex, is the main stimulator of the biosynthesis of glucocorticoids and androgenic corticosteroids. To some extent regulates the secretion of the mineralocorticoid aldosterone. ACTH mobilizes fats from fat depots and promotes the accumulation of glycogen in muscles.

5. Thyrotropin(thyroid-stimulating hormone, TG). Activates the function of the thyroid gland, stimulates the synthesis of thyroid hormones and hyperplasia of glandular tissue. It is thought to stimulate LH.

6. Somatotropin(somatotropic hormone, STH). This is a hormone with a direct effect on target cells of peripheral tissues. It has a pronounced protein-anabolic and growth effect. Determines the rate of development of the organism and its final size.

7. Melanotropin(melanocyte-stimulating hormone, MSH). Formed in the intermediate part of the anterior pituitary gland. Causes dispersion of pigment granules (melanosomes) in melanocytes, which is manifested by darkening of the skin. Participates in the synthesis of melanin. In addition, it affects protein and fat metabolism.

Let me remind you that the activity of the adenohypophysis is controlled by a number of hypothalamic factors (peptide hormones). They stimulate (liberins, releasing factors) or inhibit (statins) their secretory activity.

There are several groups standard forms endocrinopathies of the adenohypophysis: 1) by origin: primary (pituitary) or secondary (hypothalamic); 2) according to the level of hormone production and (or) the severity of its effects: hypofunctional (hypopituitarism) or hyperfunctional (hyperpituitarism); 3) according to the time of occurrence in ontogenesis: early (develop before puberty) or late (occur in adults); 4) according to the scale of the lesion and dysfunction: disruption of the production (effects) of one hormone (partial endocrinopathies), several (subtotal) or all (total panhypo- or panhyperpituitarism).

Total hypopituitarism

1. Simmonds disease(hypothalamic-pituitary cachexia). The disease is based on diffuse damage (infection, tumor, trauma, hemorrhage) of the hypothalamic-pituitary region with loss of function of the adenohypophysis and failure of the peripheral endocrine glands. Characterized by severe exhaustion (cachexia), premature aging, metabolic and trophic disorders. Women aged 30-40 years are most often affected.

Pathogenesis. Lack of pituitary tropic hormones leads to sharp decline functions of peripheral endocrine glands. A decrease in somatotropin production causes exhaustion. Loss of gonadotropic function leads to ovarian failure, amenorrhea, atrophy of the uterus and vagina. Deficiency of thyrotropin, as a result - pituitary myxedema. A decrease in corticotropin production leads to the development of adrenal insufficiency up to Addisonian crises. Typically, this is the sequence of progression of pituitary insufficiency (loss of gonadotropic, somatotropic, thyrotropic and corticotropic functions). It is important to emphasize that the adenohypophysis has large functional reserves. Therefore, obvious symptoms of pituitary insufficiency develop only when 75–90% of the glandular tissue is destroyed. Clinically detectable general weakness, adynamia, emaciation, muscle atrophy, lack of appetite, drowsiness, amenorrhea, apathy. In the internal organs, changes in the form of hypofunction and atrophy are also sharply expressed (bradycardia, decreased blood pressure, suppression of secretion in the gastrointestinal tract, splanchnoptosis, etc.).

2. Sheehan's disease- postpartum hypopituitarism. The disease is usually based on significant and not timely compensated blood loss during childbirth (in combination with postpartum sepsis), accompanied by vasospasm of the anterior pituitary gland (APG). PDH hyperplasia during pregnancy is important. With prolonged vascular spasm, ischemic necrosis of the pituitary gland and a picture of pituitary cachexia develop. Unlike Simmonds' disease, it is not characterized by severe exhaustion and disorders of the gonads are relatively less pronounced.

Partial hypopituitarism

Strictly monohormonal forms of pathology are almost never found. Let us consider only the most common diseases, which are based on partial adenohypophyseal insufficiency.

Pituitary dwarfism. The main manifestation of this disease is a sharp retardation of growth associated with an absolute or relative deficiency of somatotropin. Frequency from 1:30005000 to 1:30000. In a broader sense, dwarfism is a disorder of growth and development, the occurrence of which can be caused not only by a deficiency of GH in connection with the pathology of the pituitary gland itself, but also by a violation of the hypothalamic regulation of its functions, and disturbances in tissue sensitivity to this hormone.

Most forms of pituitary dwarfism are related to genetic diseases. The most common is panhypopituitary dwarfism, which is inherited predominantly in a recessive manner. Genetic dwarfism with isolated growth hormone deficiency occurs occasionally (more common in Africa and the Middle East).

In the development of secondary dwarfism, as a symptom of any disease, chronic infections, intoxications, and poor nutrition are important.

A large group of patients with dwarfism consists of patients with various types of organic pathology of the central nervous system that arose in utero or in early childhood (underdevelopment of the pituitary gland, its cystic degeneration, atrophy due to compression by a tumor). Dwarfism can be caused by traumatic damage to the hypothalamic-pituitary region (intrauterine, birth or postnatal), which often occurs during multiple pregnancies, as well as during childbirth in the breech, leg presentation or in the transverse position with rotation on the leg (this is the mechanism of childbirth in 1/3 patients with dwarfism). Infectious and toxic damage is important (intrauterine viral infections, tuberculosis, toxoplasmosis; diseases in early age, neonatal sepsis, meningo- and arachnoencephalitis).

Clinic. A sharp lag in growth and physical development are the main manifestations of pituitary dwarfism. Patients are born with normal weight and body length and begin to lag in growth from 2–4 years of age. Height below 130 cm for men and 120 cm for women is considered to be dwarfism. For pituitary dwarfism, in addition to small absolute sizes The body is characterized by low annual dynamics of growth and physical development. The physique is proportional, but the proportions of the patients’ bodies are characteristic of childhood. The skin is pale, often with a yellowish tint, dry (due to thyroid insufficiency). The most important feature The disease is a delay in the timing of differentiation and ossification of the skeleton. In this regard, the dental system also suffers: there is a late change of milk teeth. The genital organs in most patients are severely underdeveloped, but malformations are rare. Sexual insufficiency is accompanied by underdevelopment of secondary sexual characteristics and decreased sexual feelings, absence of menstruation.

Thyroid insufficiency is a fairly common sign of dwarfism. Intellect in most cases is not impaired, although some infantilism in behavior is often noted. The EEG in patients is characterized by features of immaturity, long-term preservation of a high “childish” voltage; unevenness of the alpha rhythm in amplitude and frequency; a sharp increase in the content of slow (theta and delta) rhythms.

Treatment. This is a long process. To obtain the effect, two basic principles must be observed:

1) maximum approximation of treatment-induced development to physiological conditions; 2) sparing the epiphyseal growth zones. The main type of pathogenetic therapy for pituitary dwarfism is the use of human growth hormone (human and primate somatotropin is used). For treatment with somatotropin, patients are selected with proven deficiency of endogenous growth hormone, with skeletal differentiation not exceeding the level characteristic of 13–14 years. In addition, the most important means of treating dwarfism is the use of anabolic steroids (nerabol, nerobolil), which stimulate growth by enhancing protein synthesis and increasing the level of endogenous growth hormone. In the presence of hypothyroidism, thyroid drugs are prescribed in parallel. When treating boys, the next step is the administration of human chorionic gonadotropin. Girls over 16 years of age are usually prescribed estrogens. The final stage of treatment (after closure of the growth zones) is the constant administration of therapeutic doses of sex hormones corresponding to the patient’s gender, with the aim of the full development of the genital organs.

Neuroendocrine obesity. This form of pathology includes numerous variants that differ in their pathogenetic mechanisms. Many of them are now believed to be based on insufficient biosynthesis in the adenohypophysis of the fat-mobilizing polypeptide lipotropin as a result of damage to the pituitary gland itself or the hypothalamic centers with secondary involvement of the pituitary gland. Pituitary obesity is characterized by excessive fat deposition on the abdomen, back and proximal extremities with relative “thinness” in the distal parts - forearms and legs.

Other endocrine glands are also involved in the progression of various forms of the disease. Hyperinsulinism is characteristic. The level of somatotropin decreases and the level of corticotropin increases. The gonadotropic function of the pituitary gland also decreases, resulting in hypogonadism.

Adiposogenital dystrophy. It develops more often in boys. This disease manifests itself in two main syndromes - obesity and hypogonadism. Such a pathology can be considered an independent disease only if its symptoms appeared in childhood and the cause of the disease could not be established. When establishing the nature of the process that damages the pituitary gland (inflammation, tumor, etc.), obesity and hypogonadism are considered as symptoms of the underlying disease.

The disease is based on dysfunction of the hypothalamus, which leads to a decrease in the gonadotropic function of the pituitary gland, and as a result, secondary hypogonadism. Adiposogenital dystrophy is detected more often in prepubertal age (10–12 years). The syndrome is characterized general obesity according to the “female type”: in the abdomen, pelvis, torso, face. Body proportions are eunuchoid (tall, narrow shoulders, poor muscle development, etc.). The penis and testicles are reduced in size, and cryptorchidism is often detected.

Hyperpituitarism

Overproduction of adenopituitary hormones, as a rule, is partial in nature and is expressed in the following most common forms.

Gigantism- a disease that occurs in children and adolescents with unfinished physiological growth. Pituitary gigantism is based on excessive secretion of somatotropin in the early stages of development of the body. Height above 200 cm in men and 190 in women is considered pathological. Gross disproportions of physique are usually not observed. However, the forearms and lower legs are characterized by excessive relative length, the head is relatively small, with an elongated face.

At the beginning of the disease, the muscular system is well developed, but later muscle weakness and fatigue are revealed. In most cases, hyperglycemia is observed, and diabetes mellitus may develop. From the genital area - hypogenitalism to varying degrees. The disease is based on tumor processes (eosinophilic adenoma) and hyperplasia of eosinophilic cells of the PDG, associated with excessive stimulating influence of the hypothalamus.

After ossification of the epiphyseal cartilages, gigantism, as a rule, turns into acromegaly. The leading sign of acromegaly is accelerated growth of the body, but not in length, but in width, which is manifested in a disproportionate periosteal increase in the bones of the skeleton and internal organs, which is combined with characteristic violation metabolism. A characteristic feature acromegaly, of course, is also increased secretion of growth hormone. However, in 8% of cases the disease develops with normal levels of growth hormone. This is explained by a relative increase in the content of a special form of the hormone, which has a greater biological activity.

Partial acromegaly, manifested by enlargement of individual parts of the skeleton or organs, is usually not associated with excess secretion of growth hormone, but is caused by congenital local hypersensitivity of tissues.

Persistent galactorrhea-amenorrhea syndrome
(SPGA, persistent lactation syndrome)

SPHA syndrome is characteristic clinical symptom complex, developing in women due to a long-term increase in the secretion of prolactin. In rare cases, a similar symptom complex develops with normal serum levels of prolactin, which has excessively high biological activity. In men, chronic hypersecretion of prolactin occurs much less frequently than in women, and is accompanied by the development of impotence, gynecomastia, and sometimes with lactorrhea.

In the last 20 years, it has become clear (thanks to methods of radioimmune determination of prolactin, tomography of the sella turcica) that chronic hyperproduction of pituitary prolactin accompanies every third case female infertility and can be either the underlying disease or a consequence of a number of endocrine and non-endocrine diseases with secondary involvement of the hypothalamus and pituitary gland. SPGA is a disease of young women, extremely rare in childhood and old age (the average age of patients is 25–40 years). The disease is diagnosed much less frequently in men.

The genesis of the disease is heterogeneous. It is assumed that the basis of SPGA, caused by primary lesion hypothalamic-pituitary system, lies a violation of the tonic dopaminergic inhibitory control of prolactin secretion. The concept of primary hypothalamic genesis suggests that a decrease or absence of the inhibitory effect of the hypothalamus on the secretion of prolactin leads first to hyperplasia of prolactophores, and then to the formation of pituitary prolactinomas. The possibility of persistence of hyperplasia or microprolactinoma that does not transform into the subsequent stage of the disease (i.e., macroprolactinoma - tumor) is allowed. Neuroinfection and skull trauma, including in the perinatal period, are also not excluded as etiological factors.

The main symptom is a violation menstrual cycle and/or infertility. The first varies from opso-, oligomenorrhea to amenorrhea. Menstrual cycle disorders are especially clearly detected during chronic periods. stressful situations (conflict situations, chronic diseases). Galactorrhea is rarely the first symptom of SPGA (no more than 20% of patients). Its degree varies from abundant, spontaneous, to single drops with strong pressure. Various nonspecific complaints are often detected: increased fatigue, weakness, nagging pain in the region of the heart without clear localization.

Men with hyperprolactinemia consult a doctor, usually due to impotence and decreased libido. Gynecomastia and galactorrhea are rare.

Neurohypophysis hormones and their main effects

The neurohypophysis secretes two hormones: antidiuretic hormone (ADH, vasopressin) and oxytocin. Both hormones enter the pituitary gland from the anterior hypothalamus.

ADH enhances the reabsorption of water from urine in the distal parts of the renal tubules and is the most important regulator of the body’s water balance. Under the influence of ADH, the wall of the distal tubule becomes water-permeable (due to the activation of cAMP in the cells of the tubular epithelium), water is absorbed along the osmotic gradient, concentration of urine occurs and its final volume decreases. The pronounced vasopressor effect of ADH is realized only at its concentrations many times higher than antidiuretic concentrations. Under physiological conditions, the vasopressor effect is not manifested. The main regulating factor of ADH secretion is blood osmotic pressure. When increasing osmotic pressure blood, ADH secretion increases, water reabsorption in the renal tubules is stimulated and blood hyperosmia is eliminated.

Oxytocin causes contraction of the muscles of the uterus and myoepithelial cells of the mammary glands. Its effect on the uterus is manifested mainly in initiating the process of childbirth. During pregnancy, the uterus is protected from the effects of oxytocin by progesterone. The secretion of oxytocin is stimulated by impulses during stretching of the birth canal, irritation of the external genitalia and nipples during breastfeeding.

Hyposecretion of ADH. A manifestation of ADH deficiency is diabetes insipidus. Its causes and mechanisms are varied, but in primary forms, disorders always occur in the hypothalamus, and not in the neurohypophysis.

Based on etiology, there are three forms of diabetes insipidus: 1) the primary form, associated with tumors of the hypothalamus, exposure to various damaging factors or degeneration of the hypothalamic nuclei; 2) familial (hereditary form), found in two variants: a) hereditary enzyme defect and inability to synthesize ADH; b) hereditary defect of renal ADH receptors (sensitivity to the hormone is blocked); 3) nephrogenic form associated with acquired pathology of the renal tubules.

The main manifestation of diabetes insipidus is constant polyuria, reaching 20 liters of urine per day or more. It is accompanied by a secondary, pronounced thirst (polydipsia), sometimes acquiring a dominant behavioral character (drinking dirty water, urine).

Hypersecretion of ADH. With this pathology, “hyperhydropexic syndrome” (Parhon syndrome) or “dilute hyponatremia syndrome” (Schwartz syndrome) occurs. Their genesis is associated with brain damage due to increased intracranial pressure, after infectious diseases, and also as a result of ectopic production of ADH. The disease is manifested by oliguria, overhydration and hyponatremia associated with hemodilution.

Adrenal dysfunction

The adrenal cortex produces several steroid hormones—corticosteroids; The medulla produces biogenic monoamines - catecholamines.

The adrenal cortex consists of three zones: glomerular, fascicular and reticular.

Zona glomerulosa synthesizes mineralocorticoids, the main of which is aldosterone. The main point of application of its action is the kidneys; it also acts on the salivary glands, gastrointestinal tract, and cardiovascular system. In the kidneys, aldosterone stimulates tubular reabsorption of sodium and excretion of potassium, hydrogen, ammonium and magnesium ions.

Beam zone produces glucocorticoids (GC) - hydrocortisone (cortisol) and corticosterone. GCs promote the absorption of carbohydrates in the intestine, inhibit their conversion into fats in the liver, promote the accumulation of glycogen in the liver, and weaken the utilization of glucose in the muscles. GCs activate protein synthesis in the liver and at the same time have a pronounced inhibitory synthesis and catabolic effect on muscle proteins, connective tissue, lymphoid and other tissues. GCs have a complex effect on fat metabolism. In addition to inhibiting lipogenesis and enhancing the mobilization of fat from the depot and ketogenesis, they have a permissive effect on the fat-mobilizing effect of catecholamines, and with prolonged excess they contribute to increased fat deposition with its characteristic topography (in the torso, face). HAs also affect water-electrolyte metabolism. Having a weak mineralocorticoid effect, they increase sodium reabsorption and potassium excretion by the kidneys, inhibit the release of ADH, and therefore increase diuresis; lower the renal threshold for glucose and lead to glucosuria in normoglycemia. Under pathological conditions and with prolonged exposure to significant doses of exogenous hormones, GCs exhibit a number of other properties: 1) anti-inflammatory, 2) antiallergic and immunosuppressive, 3) suppress the reproduction and activity of fibroblasts, 4) increase the secretion of hydrochloric acid and pepsin.

Mesh zone The adrenal glands synthesize male sex hormones (androgens) - dihydroepiandrosterone, dihydroepiandrosterone sulfate, etc., as well as trace amounts of female sex hormones - estrogens. These adrenal steroids are capable of being converted into testosterone. The adrenal glands themselves produce little of this substance, as well as estrogens (estradiol, estrone). However, adrenal androgens can serve as a source of estrogens produced in subcutaneous fat, hair follicles, and mammary glands. It is important to note that androgen secretion is under the control of ACTH. However, unlike cortisol, in the system of regulation of their synthesis, feedback is not realized to a noticeable extent and, with an increase in their level, inhibition of ACTH synthesis does not occur.

Hypofunction of the adrenal cortex

I will dwell only on some diseases associated with hypofunction of the NP cortex.

Acute cortex failure NP(Waterhouse-Fridriksen syndrome). Develops in newborns, children and young people. In newborns, the disease can be caused by hemorrhage into the adrenal cortex during difficult childbirth, accompanied by asphyxia or forceps, or eclampsia. Hemorrhage into the adrenal cortex is possible with infectious diseases (influenza, measles, scarlet fever, diphtheria), sepsis, hemorrhagic diathesis, thrombosis of the adrenal veins, etc. It also develops when a hormonally active tumor of the NP cortex is removed (in the case of a functionally defective remaining adrenal gland).

Pathogenesis. As a result sudden occurrence deficiency of gluco- and mineralocorticoids, severe metabolic disorders characteristic of Addison's disease catastrophically quickly arise, a condition resembling rapidly develops severe form Addisonian crisis, which often leads to death.

Manifestations. Depending on the predominance of symptoms of damage to a particular system, they distinguish: 1) gastrointestinal form (nausea, vomiting, diarrhea, dehydration, decreased blood pressure); 2) cardiovascular form (tachycardia, decreased blood pressure, collapse); 3) meningoencephalitic form (delirium, convulsions, coma); 4) mixed form (most common).

Principles of therapy for acute cortical deficiency with NP: 1) replacement of corticosteroid deficiency; 2) correction of water-electrolyte metabolism (elimination of tissue dehydration, Na-K balance); 3) increased blood pressure; 4) fight against infection.

Chronic failure NP cortex(Addison's disease). The disease was described by Addison in 1885. It may be associated with a bilateral tuberculosis process, tumor metastases, toxic lesions, and amyloidosis. Atrophy of autoimmune origin is common. Many patients have antibodies against steroidogenic cells, and hypocortisolism is combined with hypogonadism. Chronic insufficiency of the NP cortex can occur with long-term corticosteroid therapy for various diseases. Secondary (central) forms of NP deficiency can be caused by ACTH deficiency due to damage to the adenopituitary gland or hypothalamus (rarely). Pituitary hypocortisolism may be a component of panhypopituitarism in severe pituitary lesions. Cases of cortisol resistance associated with abnormalities of glucocorticoid receptors have also been reported. Chronic hypocortisolism is manifested by asthenia, apathy, decreased performance, muscle weakness, arterial hypotension, anorexia, weight loss. Polyuria is often observed in combination with renal failure.

Hyperpigmentation of the skin and mucous membranes is a hallmark of chronic primary (peripheral) adrenal insufficiency. Increased deposition of melanin is observed on open and closed parts of the body, especially in places of friction of clothing, on the palmar lines, in postoperative scars, on the mucous membranes of the oral cavity, in the area of the areolas of the nipples, anus, external genitalia, on the back surfaces of the elbow and knee joints. The skin usually takes on a bronze coloration, but can be golden brown or have an earthy tint. Hyperpigmentation is never found in secondary adrenal insufficiency. Darkening skin- this is almost always one of the first manifestations of the disease. The reason is a sharp increase in ACTH secretion in response to a decrease in hormone secretion by the NP cortex. ACTH, acting on melanophores, causes increased pigmentation.

The manifestation of total hypocortisolism is based on the insufficiency of the effects of all NP hormones. Muscle weakness is associated with electrolyte imbalance (aldosterone deficiency) and hypoglycemia (BG deficiency), as well as a decrease muscle mass(due to androgen deficiency). Arterial hypotension is associated with hyponatremia and loss of the permissive effect of glucocorticosteroids. As a consequence of this, there is a decrease in the reactive properties of the vascular wall to pressor influences (catecholamines). Hypotension may be aggravated by weakening of the contractile function of the heart.

Loss of sodium is accompanied by polyuria, hypohydration, and blood thickening. Along with arterial hypotension, deterioration of the rheological properties of blood leads to a decrease in glomerular blood flow and effective filtration pressure. Hence, along with polyuria, insufficiency of the excretory function of the kidneys may occur.

On the part of the gastrointestinal tract, profuse diarrhea is often observed, which is a consequence of insufficient secretion of digestive juices and intense release of sodium ions in the intestines (lack of aldosterone).

Hyperfunctional states of the NP cortex

There are two forms of excess aldosterone secretion: primary and secondary hyperaldosteronism.

Reason primary hyperaldosteronism(Conn's syndrome) is usually a hormonally active tumor originating from the zona glomerulosa. Manifestations of primary hyperaldosteronism are reduced to three main groups of symptoms: cardiovascular, renal, and neuromuscular. The main manifestations of these disorders are renal sodium retention and potassium loss. To replenish the deficiency of potassium in the blood and extracellular fluid, the latter leaves the cells. Instead of potassium, sodium, chlorine, and hydrogen protons enter the cells. The accumulation of sodium in the cells of the vascular walls leads to their hyperhydration, narrowing of the lumen, increased peripheral resistance and, consequently, increased blood pressure. Arterial hypertension is also promoted by an increase in the sensitivity of the contractile elements of the vascular walls to the action of pressor amines. As a result of hypertension, especially often in children, changes in the fundus of the eye occur, leading to visual impairment including blindness. Heart rhythm disturbances are observed. The ECG shows changes characteristic of hypokalemia (decreased T wave, high U). In the initial stage of the disease daily diuresis downgraded Then oliguria is replaced by persistent polyuria, which is caused by degeneration of the epithelium of the renal tubules and a decrease in their sensitivity to ADH. Edema with Conn's syndrome, as a rule, does not occur. This is explained by polyuria and the fact that the osmolarity of the intercellular fluid changes little, while the intracellular fluid increases.

Disturbances in the neuromuscular system are usually manifested by muscle weakness, paresthesia, and convulsions.

Secondary hyperaldosteronism . Under physiological conditions, it occurs under severe stress, pregnancy, menstruation, hyperthermia, etc. Pathological hyperaldosteronism occurs in three groups of diseases: those accompanied by hypovolemia, renal ischemia, and impaired liver function (cirrhosis). The accumulation of aldosterone in liver diseases is due to the fact that it is metabolized there. In addition, with liver pathology, the amount of glucuronic compounds of the hormone decreases, and consequently, the content of its active form (free) increases.

In particular, the first group includes acute blood loss, various forms of heart failure, nephrosis with severe proteinuria and hypoproteinemia. In these cases, increased aldosterone production is associated with activation of the renin-angiotensin system in response to hypovolemia. Secondary hyperaldosteronism also manifests itself as sodium retention, hypertension, overhydration and other similar symptoms. However, with it, unlike Conn's syndrome, there is a high level of renin and angiotensin in the blood and edema develops.

Overproduction of glucocorticoids. Itsenko–Cushing's disease. This pathology is caused by central hypercortisolism. One of the causes of this disease is a hormone-producing tumor of the anterior pituitary gland - basophilic adenoma. In some cases, the disease is associated not with a pituitary tumor, but with excessive production of corticoliberin by the corresponding nuclei of the hypothalamus. An excess of this factor leads to increased formation of ACTH by basophilic cells of the anterior pituitary gland, excessive stimulation of the zona fasciculata and reticularis of the NP and bilateral hyperplasia of these glands.

Manifestations of the disease are associated with hyperproduction of glucocorticoids. Excessive formation of androgens and mineralocorticoids is also of some importance. IK disease is more common in young women.

From nonspecific symptoms patients are concerned about general malaise, weakness, increased fatigue, headache, pain in the legs, back, and drowsiness. The patient’s appearance is characteristic: a round “moon-shaped” purplish-red face, moderate hypertrichosis (in women), obesity (predominant fat deposition in the face, neck, upper half of the body). Atrophic, receding purplish-red or purple “stretch stripes” (striae) on the skin of the abdomen, shoulders, mammary glands, and inner thighs are also characteristic. Osteoporosis is often detected - damage to the protein matrix of bones with secondary demineralization. "Striae" and bone changes associated with the protein-catabolic and antianabolic effects of excess glucocorticoids. As a rule, the cardiovascular system suffers. Persistent high arterial hypertension develops with secondary disorders: cerebrovascular accident, retinopathy, wrinkled kidney, overload form of heart failure. In the genesis of cardiac disorders, the so-called electrolyte-steroid cardiopathy is of significant importance. It is associated with local electrolyte changes in various parts of the myocardium - an increase in intracellular sodium and a decrease in potassium. Consequently, with this pathology, the overload form of heart failure is combined with myocardial failure. The main role in cardiovascular disorders in I-C disease belongs to electrolyte imbalances, in particular sodium retention. The ECG shows changes characteristic of hypokalemia: decreased T wave, ST depression, prolongation of the QT interval, as well as signs of left ventricular hypertrophy. The immunosuppressive effect of excess GC is due to a decrease in resistance to infectious diseases with I–C disease. In addition, there is decreased glucose tolerance, hyperglycemia, and often (in 15–25% of cases) diabetes mellitus (the reason is the “contrinsular” properties of GC).

There are also disorders of the blood coagulation system: bleeding, thromboembolism. Lymphopenia, eosinopenia, and erythrocytosis are detected in the peripheral blood. In most cases, kidney function is impaired. Urine examination often reveals proteinuria, an increase in the amount shaped elements, cylindruria. A kidney biopsy reveals changes like glomerulonephritis. Very often the function of the gonads suffers. In women it is disrupted menstrual cycle according to the type of oligomenorrhea. Virilization is observed in 75% of cases. In men, phenomena of demasculinization are observed: a decrease in the size of the testicles and penis, a decrease in libido and potency, loss of body hair (pituitary gonadotropins are inhibited, as a result - a lack of testosterone in the testicles, impaired spermatogenesis).

Primary glandular (peripheral) form of hypercortisolism. This form of pathology is, as a rule, a consequence of the formation of corticosteroma - a hormonally active tumor of the adrenal cortex, emanating from the zona fasciculata and producing cortisol, or a malignant tumor. I would like to emphasize that during the development of a tumor, all zones of the NP cortex are involved (primary, total hypercortisolism). The peripheral, primary glandular form of hypercortisolism is clinically referred to as “Itsenko–Cushing syndrome.”

External manifestations I–C syndrome is similar to the symptomatology of I–C disease. The fundamental differences between them are that for disease I–It is characterized by a combination of hypercortisolism with high levels of ACTH and bilateral NP hyperplasia. With syndrome I–By a feedback mechanism, ACTH production is suppressed by the primary excess of GC and the level of ACTH in the blood is reduced.

In order to clarify the mechanism of development of the pathology, the clinic uses a test with dexamethasone (Liddle suppression test), an active analogue of glucocorticoids. In case of I-C disease, the administration of small doses (8 mg per day) suppresses the activity of the NP cortex (the release of ACTH is inhibited); with I–C syndrome, this effect is absent. Another difference between I–C syndrome: in it, unlike I–C disease, an increase in one NP with atrophy of the other is detected.

Hyperproduction of hormones in the reticular zone of the NP cortex ( adrenogenital syndrome, AGS). This type of disorder of the NP cortex occurs in two main forms: 1) congenital virilizing (virilis - male; androgenizing) hyperplasia of the NP and 2) hormonally active tumor - androsteroma (androblastoma).

Congenital form AGS. This form of pathology is associated with genetic damage to the enzyme systems involved in the synthesis of glucocorticoids, and, as a consequence, excessive formation of androgens with impaired sexual development. The disease was first described by De Crechio (1865), who discovered internal female genitalia during an autopsy of a male patient.

Congenital AGS is based on deficiencies of the enzymes 21-hydroxylase, 11-hydroxylase and 3-dehydrogenase, which are involved in the multistage synthesis of corticosteroids. As a result of the action of a recessive gene, one of the enzymes may be affected, which leads to a disruption in the formation of cortisol, the deficiency of which in the blood indirectly through the hypothalamus, as well as directly through the pituitary gland, causes excessive (compensatory) formation of corticotropin, hyperfunction and hypertrophy of the NP cortex. The formation of androgens increases sharply, in the synthesis of which the above enzymes do not participate.

There are four clinical forms diseases: 1) simple virilizing form (most common); 2) virilism with hypotonic syndrome (“salt-wasting” form, hypomineralocorticism); 3) virilism with hypertensive syndrome (rare); 4) mixed. Let me emphasize once again that in all cases the synthesis of cortisol, corticosterone and aldosterone is disrupted. Also, in all cases, the synthesis of androgens increases, which affects the development of the genital organs.

Manifestations AGS are most pronounced in girls and in most cases are detected immediately after birth (although they can appear much later). As a rule, children with this disease are born large as a result of the anabolic effect of androgens. If hyperproduction of androgens occurs during early stage fetal development, changes in the external genitalia are expressed so sharply that it can be difficult to determine the sex of the child.

If excess androgens appear only after birth, the external genitalia have a normal appearance and their change occurs gradually as NP dysfunction increases. An early sign Virilization in girls is caused by abnormal, excessive hair growth that appears at the age of 2–5 years (or earlier) - hypertrichosis (or hirsutism). In more late dates Excess androgens also affect the body structure of girls. Due to increased anabolism, rapid growth is initially observed, but as a result of premature ossification of the epiphyses of the tubular bones, growth soon stops and ultimately short stature occurs. Excessive development of muscles (shoulder girdle) is also characteristic. The mammary glands do not develop, menstruation does not occur. The voice becomes rougher, acne appears. Adult women also experience amenorrhea, atrophy of the uterus and mammary glands, and baldness in the forehead often appears.

Boys with congenital NP hyperplasia are usually born with normal differentiation of the external genitalia. Subsequently, early false puberty occurs according to the isosexual type: secondary sexual characteristics and external genitalia (macrogenitosomia) clearly develop prematurely. At the same time, due to the inhibition of the formation of pituitary gonadotropins by excess androgens, the gonads remain underdeveloped and spermatogenesis may be completely absent. Characteristic appearance: short stature, short legs, developed muscles (“Hercules child”).

In the hypotensive (salt-wasting) form of AGS, due to a sharp decrease in aldosterone production, along with the already indicated signs of AGS, serious disturbances in electrolyte balance are observed: loss of sodium, hyperkalemia, hypohydration and, as a consequence, arterial hypotension. Crises often develop with convulsions and hemodynamic disorders up to collapse.

AGS with hypertensive syndrome is characterized by a significant excess of deoxycorticosterone, which has a mineralocorticoid effect, which leads to sodium retention, potassium loss and, consequently, persistent arterial hypertension. Along with this, there are also clear signs of virilization (pseudohermaphroditism in girls, macrogenitosomy in boys). Sometimes there are also erased forms of the disease, manifested by mildly expressed symptoms: moderate hypertrichosis, menstrual irregularities.

Diagnosis of AGS is based on clinical manifestations and results of laboratory research methods. Currently, the most informative for diagnosing erased AGS forms It is necessary to determine the initial level of hormones in the blood plasma and their dynamics against the background of hormonal tests. For example, in order to clarify the source and nature of androgen hypersecretion if AGS is suspected, tests with dexamethasone and ACTH are used. In AHS, administration of dexamethasone suppresses ACTH secretion via a feedback mechanism. Decreased adrenal stimulation leads to decreased adrenal steroidogenesis and decreased synthesis of adrenal androgens. Dexamethasone is usually prescribed at a dose of 40 mg/kg body weight per day for three days. To evaluate the sample, the initial level of androgens (usually dehydroepiandrosterone and testosterone) and 17-hydroxyprogesterone in the blood (or total 17-CS, DHEA in the urine) and on the last day of the sample are determined. The test is considered positive if, while taking dexamethasone, the level of androgens and 17-hydroxyprogesterone decreases by 50% or more.

Acquired form of reticular hyperfunction is caused, as already noted, by a hormonally active tumor originating from the reticular zone of the NP and producing a large amount of androgens.

Manifestations of the disease in women coincide with congenital AGS. Unlike congenital AGS, with androsteroma there is usually no significant increase in plasma ACTH levels, but the urinary excretion of 17-ketosteroids is sharply increased (sometimes up to 1000 mg per day).

Adrenal medulla. The adrenal medulla synthesizes and secretes two hormones: adrenaline and norepinephrine. Under normal conditions, the adrenal glands secrete significantly more adrenaline (about 80%). The metabolic and physiological effects of catecholamines are diverse. They have a pronounced pressor hypertensive effect, stimulate the heart, affect smooth muscles, regulation of carbohydrate metabolism, protein catabolism, etc. Insufficiency of hormone production in the medulla of NP as an independent form of endocrinopathies practically does not occur. This is due to the fact that in the body, in addition to the medulla, the NP contains sufficient quantity chromaffin tissue capable of producing adrenaline. Excessive secretion of catecholamines occurs with a tumor arising from the medulla of the NP - pheochromocytoma and some other (rare) tumors of chromaffin tissue. Increased release of hormones can be provoked by mental or physical stress, painful stimulation and other stress factors. This disease is characterized primarily by cardiovascular disorders: tachycardia, peripheral vascular spasm and a sharp increase in blood pressure. At paroxysmal form patients feel anxiety, fear, sharp throbbing headaches; profuse sweating, muscle tremors occur, nausea, vomiting, and breathing problems are possible. Hyperglycemia is observed in the blood (glycogenolysis increases). In cases with persistently elevated blood pressure vascular changes and other disorders characteristic of severe progressive arterial hypertension occur.

Chapter 32
ETIOPATHOGENESIS OF THYROID FUNCTION DISORDERS
and parathyroid glands

General issues of the structure and function of the thyroid gland are well known from the course of physiology, histology, and experimental pathophysiology. Therefore, we will not dwell on this in detail. Let me remind you that the main hormones of the thyroid gland (TG) are iodine derivatives of the amino acid tyrosine - thyroxine (tetraiodothyronine, T4) and triiodothyronine (T3). These hormones are produced by thyrocytes (follicular cells, or A-cells of the gland).

A specific regulator of the formation and secretion of T3 and T4 is the pituitary thyroid-stimulating hormone (TSH), which in turn is under the control of hypothalamic thyrotropin-releasing hormone. In addition to TSH, the secretion of thyroid hormones is activated directly by sympathetic impulses (although not as intensely as thyrotropin). Thus, the regulating influence of the hypothalamus on the thyroid gland can be carried out both through the pituitary gland and parapituitary. Almost all T4 entering the blood is reversibly bound to serum proteins. A dynamic equilibrium is established between bound and free T4; in this case, hormonal activity is manifested only in the free fraction. T3 binds to blood proteins less readily than T4. Reception of hormones occurs inside the cell. Having penetrated into it, a significant part of T4 loses one iodine atom, passing into T3. Nowadays the dominant point of view is that the main hormone acting in the cell nucleus is T3. In almost all indicators of thyroid hormone activity, T3 is significantly (3–10 times) superior to T4.

However, both in the gland itself and in the “target cells,” along with the synthesis of the active form of T3, a certain amount of so-called “reversible” (reversible) triiodothyronine rT3 is formed, which is practically devoid of specific hormonal activity, but is capable of occupying nuclear receptors. Thus, thyroxine entering the cell can partially exert its specific effect on it; it partially becomes more active, turning into T3, and is partially inactivated, turning into rT3 (the normal concentration of the latter in the blood is about 0.95 nmol/l).

Metabolic effects of thyroid hormones:

1. The influence of thyroid hormones on oxidative processes is very pronounced. They are noticeably intensified in the heart, liver, kidneys, and skeletal muscles. There is no or insignificant activating effect in the uterus and brain.

2. Heat production naturally increases (calorigenic effect of thyroid hormones). The main importance in the calorigenic effect is given to general increase the intensity of processes associated with the formation and release of energy, increased cardiac activity, activation of the synthesis of Na-K-dependent ATPase and ion transport through biomembranes.

3. Thyroid hormones also influence protein metabolism. In general, under physiological conditions they have a pronounced proteanabolic effect. The stimulating effect on the secretion and effects of growth hormone is also essential. On the contrary, high concentrations of T3 and T4 have a protein-catabolic effect: activation of proteases, protein breakdown, gluconeogenesis from amino acids, and an increase in the level of residual nitrogen.

4. The effect on fat metabolism is characterized by increased mobilization of fat from the depot, activation, activation of lipolysis and fat oxidation, as well as inhibition of lipogenesis.

5. Lipid metabolism is characterized, along with the activation of cholesterol synthesis, by increasing its use and secretion by the liver (hence, the level of cholesterol in the blood decreases).

6. Thyroid hormones have an effect on carbohydrate metabolism similar to adrenaline: they increase the breakdown of glycogen, inhibit its synthesis from glucose and resynthesis from lactic acid. They stimulate the absorption of carbohydrates in the intestine, having a generally hyperglycemic effect.

Physiological effects. Of the physiological effects of T3 and T4, the most pronounced are the activation of sympathoadrenal and cardiovascular systems. It is the strengthening of sympathoadrenal influences that mainly determines the hyperdynamic state of the circulatory system. These hormones also affect the hematopoietic system, stimulating hematopoiesis, the digestive system, increasing juice secretion and appetite, skeletal muscles, the liver, and gonads.

Hypothyroidism

An insufficient level of thyroid hormones in organs and tissues leads to the development of hypothyroidism - a disease first described by V. Gall in 1873. The term “myxedema”, owned by V. Ord (1878), refers only to mucous swelling of the skin. There are primary (peripheral), secondary (central pituitary) and tertiary (central hypothalamic) hypothyroidism.

The causes of peripheral hypothyroidism are very diverse: 1) congenital hypo- or aplasia of the gland; 2) damage to gland tissue by a pathogenic agent; 3) absence or block of enzymes necessary for the synthesis of hormones; 4) lack of the necessary specific substrate (iodine); 5) extraglandular causes (transport communication, hormone inactivation, etc.).

Central hypothyroidism can be caused by tumors and other lesions of the hypothalamus. More often, secondary hypothyroidism occurs as part of a general pituitary pathology (mainly the anterior lobe) and is combined with hypogonadism and hypocortisolism. Currently, primary hypothyroidism, which occurs on the basis of chronic autoimmune thyroiditis, is the most common in adults. In chronic thyroiditis, the thyroid tissue, having passed the stage lymphoid infiltration, gradually atrophies and is replaced by fibrous. At the same time, iron can and mind

Hypofunction of the parathyroid glands. The lack of function of the parathyroid glands, i.e. severe hypoparathyroidism, causes the development of parathyroid tetany. In the experiment, it is recreated by removing the glands in dogs and cats. In 1-2 days. After the operation, the animals become lethargic, refuse food, they experience thirst, decreased body temperature, and shortness of breath. Due to a decrease in calcium concentration in the blood, the ratio of monovalent (Na+, K+) and divalent (Ca2+, Mg2+) ions changes. The result of this is a sharp increase in neuromuscular excitability. Muscle rigidity occurs and gait is disturbed. In this case, multiple fibrillary contractions of the muscles of the whole body are observed, which are then joined by seizures. The latter turn into tonic convulsions, and opisthotonus develops (sharp arching of the body with the head thrown back). Convulsive contractions can also spread to internal organs (pylorospasm, laryngospasm). During one of these attacks, animals die, usually as a result of a spasm of the respiratory muscles.

Against the background of hypocalcemia, the content of inorganic phosphorus in the blood increases. Disorders of mineral metabolism are caused by inhibition of bone resorption, calcium absorption in the intestine and increased reabsorption of phosphates in the nephron tubules.

In the pathogenesis of parathyroid tetany, disturbances in the detoxification function of the liver are of particular importance. Feeding meat to dogs whose parathyroid glands have been removed increases tetany due to insufficient neutralization of nitrogen metabolism products, in particular inhibition of the liver’s ability to convert ammonium into urea.

If there are additional parathyroid glands (in rabbits, rats) or if a lobule of the parathyroid gland is preserved during surgery, animals develop chronic hypoparathyroidism, clinical picture which is known as parathyroid cachexia. It is characterized by loss of body weight, refusal to eat (anorexia), increased neuromuscular excitability, diarrhea and various trophic disorders.

Hypoparathyroidism in humans most often develops as a result of accidental damage or removal of the parathyroid glands during surgical intervention on the thyroid gland. Relative hypofunction of the glands is observed in cases of intensive growth, during pregnancy, lactation and in other conditions characterized by an increased need for calcium salts in the body.

The pathogenesis and clinical picture of hypoparathyroidism in humans are similar to those observed in the experiment. An increase in neuromuscular excitability is determined by the appearance of muscle contractions during irritation motor nerves galvanic current of a certain strength, squeezing the hand above the elbow or lightly tapping the skin at the exit of the facial nerve in front of the external auditory canal.

Hyperfunction of the parathyroid glands. In hyperparathyroidism, due to increased secretion of parathyroid hormone, the formation and activity of osteoclasts, which carry out bone resorption, are enhanced, and the formation of osteoblasts, which take part in the formation of new bone tissue, is inhibited. At the same time, the absorption of calcium in the intestine increases, the reabsorption of phosphates in the nephron tubules decreases, the content of soluble calcium salts in bone tissue and insoluble calcium phosphate in various organs, including the kidneys, increases.

Hyperparathyroidism in experimental animals is recreated by administering an extract of the parathyroid glands or purified parathyroid hormone. Influenced high doses hormone level of calcium in the blood reaches 5 mmol/l, i.e. it becomes 2 times higher than normal; the concentration of inorganic phosphorus decreases; the excretion of phosphorus in the urine increases. Although parathyroid hormone slightly activates the tubular reabsorption of calcium ions, their excretion in the urine is enhanced due to significant hypercalcemia. Dehydration, vomiting, fever, and acute renal failure occur, as a result of which the animals die.

Experimental chronic hyperparathyroidism differs from acute intoxication parathyroid hormone. In this case, progressive thinning of bone tissue (osteoporosis), deposition of calcium salts in the kidneys, lungs, heart and other internal organs are observed, up to their complete calcification. The walls of blood vessels become hard and brittle, and blood pressure increases. Animals die, as a rule, from kidney damage.

The occurrence of hyperparathyroidism in humans is associated with adenoma or hyperplasia of the parathyroid glands. For generalized fibrous osteodystrophy, which develops in this case, is characterized by pain in the muscles, bones and joints, softening of the bones, and severe deformation of the skeleton. Mineral components are washed out of bone tissue and deposited in muscles and internal organs (this phenomenon is figuratively called the movement of the skeleton into soft fabrics). Nephrocalcinosis develops, narrowing of the lumen of the nephron tubules and their blockage with stones (nephrolithiasis), and as a result, severe renal failure. Due to the deposition of calcium salts in the walls of the great vessels, hemodynamics and blood supply to tissues are disrupted.