Hypofunction and hyperfunction of the parathyroid glands. Diseases of the parathyroid glands: hyperfunction and hypofunction Treatment of parathyroid gland disorders

The main symptom of hypoparathyroidism caused by insufficiency of the parathyroid glands is hypocalcemia. As a result, neuromuscular excitability increases, which is manifested by attacks of tonic convulsions, spasmophilia (respiratory muscle spasms). Neurological and cardiovascular disorders may occur.

Calcitonin– a polypeptide consisting of 32 amino acid residues. It is synthesized in the parafollicular cells of the thyroid gland or in the cells of the parathyroid glands. Calcitonin secretion increases with increasing Ca 2+ concentration and decreases with decreasing Ca 2+ concentration in the blood.

Calcitonin is a parathyroid hormone antagonist. Target organs: bones, kidneys, intestines. Effects of calcitonin:

inhibits the release of Ca 2+ from bone, reducing osteoclast activity;

promotes the entry of phosphate into bone cells;

stimulates the excretion of Ca 2+ by the kidneys in the urine.

The rate of calcitonin secretion in women depends on the level of estrogen. With a lack of estrogen, the secretion of calcitonin decreases, which leads to the development of osteoporosis.

Calcitriol(1,25-dihydroxycholecalciferol) is a steroid hormone synthesized in the kidneys from the low-active precursor 25-hydroxycholecalciferol. Target organs: intestines, bones, kidneys. Effects of calcitriol:

promotes the absorption of Ca 2+ into intestines, stimulating the synthesis of calcium-binding protein;

V bones stimulates the destruction of old cells by osteoclasts and activates the uptake of Ca 2+ by young bone cells;

increases the reabsorption of Ca 2+ and P in kidneys.

The final effect is increase in Ca levels 2+ in blood.

Adrenal hormones Adrenal medulla hormones

In the adrenal medulla, chromaffin cells synthesize catecholamines- dopamine, adrenaline and norepinephrine. The immediate precursor of catecholamines is tyrosine. Norepinephrine is also formed in the nerve endings of the sympathetic nervous tissue (80% of the total amount). Catecholamines are stored in granules of adrenal medulla cells. Increased secretion of adrenaline occurs during stress and decreased blood glucose concentrations.

Adrenaline is primarily a hormone, norepinephrine and dopamine are mediators of the sympathetic part of the autonomic nervous system.

Biological effect

The biological effects of adrenaline and norepinephrine affect almost all functions of the body and consist in stimulating the processes necessary for the body to withstand emergency situations. Adrenaline is released from adrenal medulla cells in response to signals from the nervous system coming from the brain during extreme situations (such as fight or flight) that require active muscle activity. It should instantly provide the muscles and brain with a source of energy. Target organs are muscles, liver, adipose tissue and the cardiovascular system.

There are two types of receptors in target cells on which the effect of adrenaline depends. The binding of adrenaline to β-adrenergic receptors activates adenylate cyclase and causes changes in metabolism characteristic of cAMP. The binding of the hormone to α-adrenergic receptors stimulates the guanylate cyclase signal transduction pathway.

In the liver adrenaline activates the breakdown of glycogen, resulting in a sharp increase in the concentration of glucose in the blood (hyperglycemic effect). Glucose is used by tissues (mainly the brain and muscles) as an energy source.

In the muscles adrenaline stimulates the mobilization of glycogen with the formation of glucose-6-phosphate and the breakdown of glucose-6-phosphate to lactic acid with the formation of ATP.

In adipose tissue the hormone stimulates the mobilization of TAG. The concentration of free fatty acids, cholesterol and phospholipids increases in the blood. For muscles, heart, kidneys, and liver, fatty acids are an important source of energy.

Thus, adrenaline has catabolic action.

Adrenaline affects cardiovascular system, increasing the strength and frequency of heart contractions, blood pressure, dilating small arterioles.

Parathyroid (parathyroid) glands are endocrine glands, usually presented in two pairs. The dimensions are equal to wheat grains, and the total mass is only a third of a gram. Adjacent to the posterior surface of the thyroid gland.

There is an abnormal location of organs directly in the tissue of the thyroid gland or even near the pericardial sac. The product of the activity of the parathyroid glands is parathyroid hormone.

Together with the thyroid hormone thyrocalcitonin, they both maintain normal calcium levels. These substances have opposite actions: parathyroid hormone increases the level of calcium in the blood, thyrocalcitonin decreases it. The same thing happens with phosphorus.

Parathyroid hormone has a diverse effect on a number of organs:

1. Bones.
2. Kidneys.
3. Small intestine.

The effect of PTH on bones is to stimulate bone resorption (resorption) through the activation of osteoclasts with a further increase in osteolytic effect. The consequence of these processes is the dissolution of crystalline hydroxyapatite, the mineral component of skeletal bones, and the release of Ca and P ions into the peripheral blood.

It is this biological mechanism that mainly provides the ability to increase calcium levels in the blood if necessary. However, his work poses a threat to humans.

Important! Excessive production of PTH leads to a negative bone balance, when resorption begins to prevail over bone formation.

As for the effect of this biologically active substance on the kidneys, it is twofold:

1. Proximal renal tubules reduce phosphate reabsorption.
2. The distal renal tubules enhance the reabsorption of calcium ions.

The intestine is also involved in the process of increasing the Ca 2+ content in the peripheral blood. PTH stimulates the synthesis of 1,25-dihydroxycholecalciferol, which is an active product of vitamin D3 metabolism. This substance promotes the growth of calcium absorption from the lumen of the small intestine, increasing the production of a special protein in its walls that can bind these ions.

The role of calcium in human metabolism

Ions of this element are involved in a large number of intracellular processes in each of the tissues of the human body. Therefore, disruption of the functions of the parathyroid glands, which control its metabolism, can lead to very serious disruptions in the functioning of the entire organism, even leading to death for it.

After all, Ca 2+ ions are needed for the following processes:

1. Muscle contractions.
2. Gives strength to bone tissue.
3. Normal functioning of the blood coagulation system.
4. Transmission of control impulses from nerves to muscle tissue.

The average adult human body contains about 1 kg of calcium. Its distribution in the body and bone tissue is shown in the diagrams below:

The calcium compounds shown in the bottom diagram differ from each other not only in composition, but also in their role in human life. Hydroxyapatite is a sparingly soluble salt that forms the basis of bone.

And phosphorus salts, on the contrary, easily dissolve in water and act as a depot of Ca 2+ ions, from which they can enter the peripheral blood in the event of a sudden deficiency.

There is always calcium in the blood and it is divided there in equal proportion between two forms:

1. Related(composed of salts and proteins).
2. Free(as a free ionized element).

There is a mutual transition between these forms, but balance is always maintained.

A person constantly loses small amounts of calcium along with nails, hair, cells of the upper layer of the epidermis, through the digestive and excretory systems, and also during blood loss. And all this must be compensated.

Another component of the system for regulating calcium levels in the blood is the hormone of parafollicular cells of the thyroid gland, calcitonin, which is a partial antagonist of PTH.

It comes into operation if the concentration of Ca 2+ ions exceeds the threshold of 2.50 mmol/l and begins to reduce it, triggering several processes:

1. Preventing the resorption of bone tissue and the removal of calcium from its composition.
2. Strengthening the removal of Na + and Ca 2+ ions, as well as phosphates and chlorides from the body by the excretory system.

Calcium metabolism is also influenced by several hormones of the gonads and adrenal glands. Most often, disorders of the parathyroid glands are manifested by hypoparathyroidism or hyperparathyroidism.

Manifestations of cancerous lesions of parathyroid tissue

Malignant neoplasms are manifested by the following symptoms:

• formation of a seal in the larynx area;
• enlargement of regional lymph nodes;
• impaired respiratory function due to partial blockage of the tracheal lumen;
• decreased esophageal patency;
• gradual deterioration in general health and rapid fatigue;
• loss of appetite and, as a result, a sharp drop in body weight;
• cancer intoxication of the body, which occurs in the later stages of cancer growth;
• low-grade body temperature.

Oncological damage to parathyroid tissue has a favorable prognosis only in the initial stages. Among stage 3-4 patients there is a very high postoperative mortality rate.

Hyperparathyroidism: aggression against the body

Hyperparathyroidism is increased activity of one or more parathyroid glands with the release of large amounts of their hormone (see). The incidence is 20 per 100 thousand population.

More often in women 50-55 years old. It occurs 3 times less often in men. The urgency of the problem is high: primary hyperparathyroidism is in 3rd place among all endocrine diseases.

This is interesting! The disease was first described by the German scientist Recklinghausen back in 1891, which is why it received the author’s name of the same name. And in 1924, Rusakov proved the relationship of a parathyroid tumor to the development of hyperparathyroidism.

Classification of hyperparathyroidism

Recklinghausen's disease can be primary, secondary and tertiary. Below is more detail about each of their forms.

Primary hyperthyroidism

The following pathologies may underlie its development:

1. Primary organ hyperplasia.
2. Hormone-secreting carcinoma.
3. Hyperfunctioning adenoma, one or more.
4. Hereditary polyendocrinopathy, which is inherited in an autosomal dominant manner (Wermer and Sipple syndromes).

In every tenth case, primary hyperparathyroidism is combined with other tumors of the endocrine glands, such as pheochromocytoma, thyroid cancer, and pituitary tumors.

Secondary hyperparathyroidism

This form of pathology is a compensatory increase in the work of the glandulae parathyroideae, developing in response to a long-term decrease in the content of calcium ions in the blood against the background of an increase in the concentration of phosphates.

This condition can be caused by the following conditions and diseases:

1. Renal form of rickets.
2. Various tubulopathies.
3. Malabsorption syndrome.
4. Various forms of osteomalacia.
5. Chronic renal failure.

Also, secondary hyperthyroidism is provoked by vitamin D deficiency of various origins, as well as problems with the absorption of Ca 2+ in the gastrointestinal tract.

Tertiary hyperparathyroidism

The reason for the development of this form of the disease is prolonged secondary hyperplasia and the autonomously functioning adenoma(s) of the parathyroid gland that has developed against its background, in which the feedback between the concentration of calcium ions in the blood and increased release of PTH is disrupted. Also, tertiary hyperparathyroidism can be provoked by various extraparathyroid neoplasms capable of ectopic release of parathyroid hormone.

What causes hyperparathyroidism?

The reasons for the development of this disease of the parathyroid gland:

• chronic kidney pathology, kidney transplantation;
• benign () or malignant neoplasm;
• hyperplasia of the parathyroid gland.

This is interesting! A tumor of the parathyroid gland leads to the development of primary hyperparathyroidism in 85% of cases, and autonomously functioning parathyroid glands - in 15%.

The mechanism of pathology development

Increased parathyroid hormone in the blood → increased release of calcium and phosphorus from bone and muscle tissue in the urine → increased porosity of bone tissue and accumulation of calcium salts in internal organs, muscle weakness. High levels of serum calcium lead to a reciprocal inhibition of the effect of pituitary antidiuretic hormone on renal structures → increased urine loss and thirst.

Inspection is a necessary stage of diagnosis

So:

1. The skin is dry, pale with an earthy tint, scratching as a result of itching, sometimes the elasticity is somewhat reduced due to loss of fluid, the hair is brittle and dull.
2. The limbs are curved, the vertebral bodies are deformed, due to this the growth is low.
3. The gait is as if the patient is rocking in a boat - “duck-like.”
4. The chest is barrel-shaped.
5. Fingers shaped like drumsticks.

General signs are nonspecific and, as a rule, do not always suggest a disease:

• weakness and drowsiness;
• rapid and dramatic weight loss up to anorexia;
• chronic fatigue and fatigue;
• fever for no apparent reason.

Overactivity of the parathyroid glands is fraught with the development of diseases from various organs:

1. Genitourinary system: urolithiasis with possible infection and further damage to the kidneys and lower urinary tract (cystitis, urethritis, prostatitis).
2. The cardiovascular system: arrhythmias and oxygen starvation of the heart muscle.
3. Gastrointestinal tract: peptic ulcer of the stomach and duodenum with complications such as bleeding or perforation.

This is interesting! Urolithiasis in 6-15% is the result of hyperparathyroidism. Untreated kidney stones lead to degeneration of the kidney tissue, which is reflected in the urine as increased levels of uric acid and nitrogen.

Clinical picture

Table 1: Symptoms of increased activity of the parathyroid glands:

Organ system	Patient's complaints
Cardiovascular	Increased heart rate and blood pressure.
Digestive	decreased appetite; nausea; vomit; diarrhea, less often - constipation; stomach ache; thirst.
Urinary	Frequent urination, incl. night
Musculoskeletal	Pain in the limbs and stiffness in the morning. Muscle weakness due to decreased muscle excitability. Aching or nagging pain in muscles, bones and joints. Fractures even with minor impacts. Loss of healthy-looking teeth.
Psychic sphere	Impaired mental abilities: memory, attention, orientation. Suppressed mood (depression). Hallucinations. Obsessive ideas of persecution.
Nervous system	Reduced skin sensitivity; feeling of numbness in the limbs; dysfunction of the pelvic organs as a result of compression of the nerve roots by curved vertebrae of the sacral spine.

It is important to know! Calcium accumulates in the walls of the arteries, causing them to become hard and inelastic. Persistent arterial hypertension develops, which leads to rupture of blood vessels with complications such as heart attack or stroke.

Diagnostics: from primitive methods to the latest technologies

As already stated, a careful examination and questioning of the patient is the first and important step of the practitioner who intends to determine the disease. It is necessary to find out the time of onset of symptoms, the course of their development, the presence of chronic diseases of the internal secretion organs and others.

It is important to know! Spasmodic pain in the abdomen can simulate acute appendicitis. A competent examination and adequate prescription of additional methods help to distinguish an acute surgical condition from the visceral form of hyperparathyroidism.

Laboratory research:

1. Biochemical blood test: increased levels of calcium, potassium, alkaline phosphatase, parathyroid hormone, creatinine clearance; decrease in phosphorus and sodium.
2. Urinalysis: increased excretion of calcium in the urine. The norm is 2.5-7.5 mmol/day.
3. Cytology - determination of the malignancy of cells under a microscope obtained after a biopsy - intravital sampling of material from the organ under study.

Instrumental diagnostic methods:

1. Scintigraphy of the parathyroid glands is an assessment of the condition of internal organs, which is based on the uniform distribution of a substance that can glow under the influence of X-rays. The image is transferred to the screen or printed on special paper. Individual parts of the organ are painted over with appropriate colors. This diagnostic method is quite sensitive - 60-90%. Disadvantage: when identifying multiple adenomas, its accuracy drops by 30-40%.

The most common cause of hyperparathyroidism is a tumor of the parathyroid gland. Main manifestations:

– hypercalcemia;
– polyuria and thirst associated with the nephrotoxic effect of high calcium concentrations, which reduce water reabsorption;

– frequent formation of kidney stones;

– calcification of the kidney tissue itself (nephrocalcinosis);

– demineralization of bones, the occurrence of pathological fractures, the formation of cysts in the bones due to high activity of osteoclasts.

Hypofunction of the parathyroid glands (hypoparathyroidism)

The causes of hypoparathyroidism are erroneous removal of the parathyroid glands during thyroid surgery or autoimmune processes. Main symptoms:
– hypocalcemia;

– increased neuromuscular excitability, leading to the development of attacks of tetany, which is manifested by convulsive contractions of skeletal and smooth muscles. Particularly dangerous for patients is spasm of the laryngeal muscles, leading to asphyxia.

TICKET

Synthesis and secretion

A necessary component of the thyroid hormone molecule is iodine. It comes from food and water in the form of iodides. The daily requirement for iodine is 150 mcg.
The synthesis of thyroid hormones occurs in the follicles of the thyroid gland. Synthesis stages:
1. Iodide is taken up by the thyroid gland from the blood using a membrane iodide pump .
2. With the participation of thyroid peroxidase, iodide is oxidized into iodine ion (J +).
3. Iodinium ion attacks tyrosine amino acid residues in the thyroglobulin protein, which makes up the bulk of the follicle colloid. Mono- and diiodotyrosyls are formed. This reaction is called organization of iodine .
4. Mono- and diiodotyrosyls condense to form tri- and tetraiodotyronyls.
5. Iodinated thyroglobulin molecules from the colloid enter the thyrocytes by pinocytosis. There, T 3 and T 4 are split off from them in lysosomes, which are secreted into the bloodstream.
The thyroid gland (TG) synthesizes and secretes mainly thyroxine (T 4) into the blood.

Regulation of secretion

Regulation by thyroid-stimulating hormone (TSH), stimulates all 5 stages of thyroid hormone synthesis, enhances the synthesis of thyroglobulin and the growth of thyroid follicles.

Transport

In plasma, 80% of T4 is associated with thyroxine-binding globulin(synthesized in the liver); 15% with thyroxine-binding prealbumin. The rest is with albumin and 0.03% remains free. T 3 has less affinity for transport proteins and its free content is 0.3%. The half-life of T 3 and T 4 is 1.5 and 7 days.

Peripheral metabolism (conversion) of thyroxine

About 80% of T 3 is formed as a result of peripheral conversion of T 4 (deiodinase) and only 20% of circulating T 3 is secreted by thyrocytes.

Mechanism of action

According to the mechanism of action, they are hormones that penetrate the cell and act through intracellular receptors. Receptors are found in almost all tissues and organs of mammals. Only the gonads and lymphatic tissue have few receptors. Thyroid hormone receptors belong to the superfamily of steroid-thyroid hormone receptors, that is, their general structure and mechanism of action are similar. However, TH receptors are different in that they are always associated with DNA. In the absence of THs, they inhibit the expression of the genes to which they are associated. Binding to the hormone converts the receptor into a transcription activator. Nuclear receptors bind predominantly to T3. This fact, as well as the existence of a mechanism for the cellular conversion of T4 to T3, allows us to consider T4 as a prohormone, and T3 as a true hormone. However, thyroxine itself is capable of producing a number of effects, apparently having its own receptors on some target cells.
Biological effects

1) Height.
a) achieving age-appropriate height;
b) act synergistically with growth hormone and somatomedins, promoting the formation of bone tissue.

2) Central nervous system (CNS).
a) the maturation of the central nervous system during the perinatal period absolutely depends on thyroid hormones;
b) with a deficiency in children, the processes of myelination, synaptogenesis and differentiation of nerve cells are disrupted, causing a pronounced slowdown in mental development. Mental changes are irreversible.

3) Basal metabolic rate (BM)
a) increase OO and O2 consumption by all tissues, excl. brain, lymph nodes and gonads;
b) increase in heat production;
c) increase the activity and synthesis of Na + /K + -ATPase, the operation of which requires a significant amount of cellular ATP. IncreaseOO.