Parathyroid glands

In 1879 the Swedish scientist S. Sandstrom described the parathyroid glands in humans and gave them the name. The parathyroid glands are vital organs. Their function is the production and secretion of parathyroid hormone (PTH) - one of the main regulators of calcium and phosphorus metabolism.

Paired upper parathyroid gland (glandula parathyroidea superior) and inferior parathyroid gland (glandula parathyroidea inferior) are rounded or ovoid bodies located on the posterior surface of each of the thyroid glands: one gland above and the other at the bottom. The length of each gland is 4-8 mm, width - 3-4 mm, thickness - 2-3 mm. The number of these glands is not constant and can vary from 2 to 7-8, on average there are four. The total mass of glands is on the average 1.18 g.

Parathyroid (parathyroid) glands differ from the thyroid gland by a lighter coloration (in children they are pale pink, in adults they are yellowish brown). Often parathyroid glands are located at the site of penetration into the thyroid gland of the lower thyroid arteries or their branches. From the surrounding tissues parathyroid glands are separated by their own fibrous capsule, from which connective tissue layers leave the glands. The latter contain a large number of blood vessels and divide the parathyroid glands into groups of epithelial cells.

Parenchyma glands is formed by the main and acidophilic parathyrocytes, forming strands and clusters, surrounded by thin bundles of connective tissue fibers. Both types of cells are considered as different stages of development of paratyrocytes. The main paratyrocytes have a polyhedral shape, a basophilic cytoplasm with a large number of ribosomes. Among these cells secrete dark (actively secreting) and light (less active). Acidophilic paratyrocytes are large, with clear contours, contain many small mitochondria with glycogen particles.

The parathyroid hormone parathyroid hormone (parathyroid hormone), a proteinaceous hormone, participates in the regulation of phosphorus-calcium metabolism. Parathyroid hormone decreases the release of calcium in the urine, increases its absorption in the intestine in the presence of vitamin D. The antagonist of parathyroid hormone is thyrecalcitonin.

[1], [2], [3], [4], [5], [6]

Embryogenesis of parathyroid glands

Parathyroid glands develop from the epithelium of paired III and IV gill pockets. At the 7th week of development, the epithelial rudiments of the corpuscles separate from the walls of the gill pockets and, in the process of growth, mix in the caudal direction. In the future, the parathyroid glands forming occupy a constant position for them on the posterior surfaces of the right and left lobes of the thyroid gland.

[7], [8], [9], [10], [11], [12],

Vessels and nerves of parathyroid glands

Blood supply of the parathyroid glands is carried out by the branches of the upper and lower thyroid arteries, as well as by the esophageal and tracheal branches. Venous blood flows along the veins of the same name. The innervation of the parathyroid glands is similar to the innervation of the thyroid gland.

Age features of parathyroid glands

The total mass of parathyroid glands in the newborn varies from 6 to 9 mg. During the first year of life, their total mass increases by 3-4 times, by the age of 5 it doubles, and 10 years triples. After 20 years, the total mass of four parathyroid glands reaches 120-140 mg and remains constant until old age. In all age periods, the mass of parathyroid glands in women is somewhat larger than that of men.

Usually, a man has two pairs of parathyroid glands (upper and lower), located on the posterior surface of the thyroid gland, outside the capsule, near the upper and lower poles. However, the number and location of parathyroid glands may vary; sometimes up to 12 parathyroid glands are found. They can be located in the tissues of the thyroid and thymus glands, in the anterior and posterior mediastinum, in the pericardium, behind the esophagus, in the carotid bifurcation area. The upper parathyroid glands have the form of a flattened ovoid, the lower ones globular. Their sizes are approximately from 6x3 to 4x1.5 - 3 mm, the total mass from 0.05 to 0.5 g, the color is reddish or yellowish brown. Blood supply of parathyroid glands is carried out mainly by branches of the lower thyroid artery, venous outflow occurs through the veins of the thyroid gland, esophagus and trachea. The parathyroid glands are sympathetic with sympathetic fibers of the recurrent and upper laryngeal nerves, parasympathetic innervation is performed by vagus nerves. The parathyroid glands are covered with a thin connective tissue capsule; The divergent partitions penetrate into the glands. They contain blood vessels and nerve fibers. Parenchyma of the parathyroid glands consists of parathyreocytes, or major cells, among which the degree of colorability distinguishes hormonal-active light or shiny, as well as resting dark cells. The main cells form clusters, strands and clusters, and in the elderly - and follicles with a colloid in the cavity. In adults, cells appear mainly on the periphery of the parathyroid glands stained with eosin, eosinophilic or oxyphilic cells, which are degenerating main cells. In the parathyroid gland, transitional forms can also be found between the main and oxyphilic cells.

The first successes in clarifying the synthesis, deciphering the structure, studying the exchange of parathyroid hormone were achieved after 1972. Parathyroid hormone is a single-chain polypeptide consisting of 84 amino acid residues, devoid of cysteine, with a molecular weight of about 9500 daltons, is formed in the parathyroid glands from the bioprecessor - hormone prodrug (proPTG) having 6 additional amino acids at the NH ₂ -kontse. ProPTG is synthesized in the main cells of the parathyroid glands (in their granular endoplasmic reticulum) and in the process of proteolytic cleavage in the Golgi apparatus becomes parathyroid hormone. Its biological activity is substantially lower than that of PTH. Apparently, there is no proPTG in the blood of healthy people, but in pathological conditions (with adenoma of the parathyroid glands) it can secrete into the blood along with PTH. Recently, the precursor proPTG-preproPTG, containing an additional 25 amino acid residues at the NH2 end, was found. Thus, preproPTG contains 115 amino acid residues, proPTG-90 and PTH-84.

Now the structure of bovine and porcine parathyroid hormone has been fully established. Parathyroid hormone from adenomas of the parathyroid glands is isolated, but its structure is only partially deciphered. There are differences in the structure of the parathyroid hormone, however, the parathormone of animals and humans exhibit cross-reactivity. A polypeptide consisting of the first 34 amino acid residues practically preserves the biological activity of the natural hormone. This allows us to assume that the remaining almost% of the molecule at the carboxyl end is not directly related to the main effects of the parathyroid hormone. A certain biological and immunological activity of parathyroid hormone is also shown by its 1-29th fragment. Immunological action is possessed also by biologically inactive fragment 53-84, ie these properties of a parathormone show at least 2 parts of its molecule.

Circulating in the blood of the parathyroid hormone is heterogeneous, it differs from the native hormone secreted by the parathyroid glands. There are at least three different types of parathyroid hormone in the blood: an intact parathyroid hormone with a molecular weight of 9500 daltons; biologically inactive substances from the carboxyl part of the parathyroid hormone molecule with a molecular weight of 7000-7500 daltons; biologically active substances with a molecular weight of about 4000 daltons.

Even smaller fragments were found in the venous blood, which indicates their formation at the periphery. The main organs in which fragments of parathyroid hormone is formed are the liver and kidneys. Fragmentation of parathyroid hormone in these organs is increased with liver pathology and chronic renal failure (CRF). In these conditions fragments of parathyroid hormone persist in the bloodstream much longer than in healthy people. The liver absorbs predominantly intact parathyroid hormone, but does not remove from the blood either carboxyl terminal or aminoterminal fragments of parathyroid hormone. The leading role in the metabolism of parathyroid hormone is played by the kidneys. They account for almost 60% of the metabolic clearance of carboxylterminal immunoreactive hormone and 45% of the aminoterminal fragment of the parathyroid hormone. The main area of metabolism of the active aminoterminal fragment of the parathyroid hormone is the bones.

Pulsed secretion of parathyroid hormone, most intense at night, was detected. After 3-4 hours from the beginning of night sleep, its content in the blood is 2.5-3 times higher than the average daily level.

The main function of parathyroid hormone is the maintenance of calcium homeostasis. At the same time, serum calcium (general and especially ionized) is the main regulator of parathyroid hormone secretion (a decrease in the level of calcium stimulates the secretion of parathyroid hormone, an increase - suppresses), that is, regulation is carried out on the principle of feedback. In hypocalcemia, the conversion of proPTG into parathyroid hormone is enhanced. In the release of parathyroid hormone, an important role is played by the magnesium content in the blood (its elevated level stimulates, and lowered - suppresses the secretion of parathyroid hormone). The main targets of parathyroid hormone are the kidneys and bones of the skeleton, but the effect of parathyroid hormone on the adsorption of calcium in the intestine, tolerance to carbohydrates, serum lipids, its role in the development of impotence, pruritus, etc., are known.

To characterize the effect of parathyroid hormone on the bone, it is necessary to give brief information about the structure of bone tissue, the peculiarities of its physiological resorption and remodeling.

It is known that the bulk of the calcium present in the body (up to 99%) is contained in bone tissue. Since it is in the bone in the form of phosphorus-calcium compounds,% of the total phosphorus content is also found in the bones. Their tissue, despite the seeming static, is constantly remodeled, actively vascularized and has high mechanical properties. Bone is a dynamic "depot" of phosphorus, magnesium and other compounds necessary to maintain homeostasis in mineral metabolism. Its structure includes dense mineral components, which are in close connection with the organic matrix, which consists of 90-95% of collagen, small amounts of mucopolysaccharides and non-collagen proteins. The mineral part of the bone consists of hydroxyapatite - its empirical formula is Ca10 (PO4) 6 (OH) 2 - and amorphous calcium phosphate.

The bone is formed by osteoblasts originating from undifferentiated mesenchymal cells. These are mononuclear cells involved in the synthesis of components of the organic matrix of bone. They are located in a monolayer on the bone surface and are in close contact with the osteoid. Osteoblasts are responsible for the deposition of the osteoid and its subsequent mineralization. The product of their life is alkaline phosphatase, the content of which in the blood is an indirect indicator of their activity. Surrounded by a mineralized osteid, some osteoblasts turn into osteocytes - mononuclear cells, the cytoplasm of which forms tubules associated with the tubules of neighboring osteocytes. They do not participate in bone remodeling, but are involved in the process of perilacuneral destruction, which is important for the rapid regulation of serum calcium levels. Bone resorption is carried out by osteoclasts - giant polynuclears, which are apparently formed by the fusion of mononuclear macrophages. It is also assumed that the precursors of osteoclasts can be hematopoietic stem cells of the bone marrow. They are mobile, form a layer in contact with the bone, located in the areas of its greatest resorption. Due to the isolation of proteolytic enzymes and acid phosphatase, osteoclasts cause degradation of collagen, destruction of hydroxyapatite and elimination of minerals from the matrix. The newly formed slightly mineralized bone tissue (osteoid) is resistant to osteoclastic resorption. The functions of osteoblasts and osteoclasts are independent, but consistent with each other, which leads to normal remodeling of the skeleton. The growth of the bone in length depends on the enchondral ossification, the growth in width and the thickness of it - from periosteal ossification. Clinical studies with ⁴⁷ Ca showed that each year up to 18% of the total calcium content in the skeleton is updated. If the bones are damaged (fractures, infectious processes), the resected bone is resorbed and a new bone is formed.

Complexes of cells involved in the local process of bone resorption and bone formation are called the basic multicellular units of remodeling (BMI - Basic multicellular unit). They regulate the local concentration of calcium, phosphorus and other ions, the synthesis of organic components of bone, in particular collagen, its organization and mineralization.

The main effect of parathyroid hormone in the bones of the skeleton is the intensification of the processes of resorption, affecting both the mineral and organic components of the bone structure. Parathyroid hormone promotes the growth of osteoclasts and their activity, which is accompanied by increased osteolytic action, and an increase in bone resorption. This dissolves the crystals of hydroxyapatite with the release of calcium and phosphorus into the blood. This process is the main mechanism for increasing the level of calcium in the blood. It consists of three components: mobilization of calcium from perilacunar bone (deep osteocytes); proliferation of osteo-progenitor cells in osteoclasts; maintaining a constant level of calcium in the blood by regulating its release from the bone (superficial osteocytes).

Thus, parathyroid hormone initially increases the activity of osteocytes and osteoclasts, strengthening osteolysis, causing an increase in the level of calcium in the blood and increasing excretion in urine and hydroxyproline. This is the first, qualitative, rapid effect of parathyroid hormone. The second effect of the action of parathyroid hormone on the bone is quantitative. It is associated with an increase in the pool of osteoclasts. With active osteolysis, there is a stimulus to increased reproduction of osteoblasts, and resorption and shaping of bone with a predominance of resorption is activated. With an excess of parathyroid hormone, a negative bone balance occurs. This is accompanied by an excessive release of hydroxyproline, a product of the degradation of collagen and sialic acids, which are part of the structure of mucopolysaccharides. Parathyroid hormone activates cyclic adenosine monophosphate (cAMP). Increased excretion of cAMP in urine after the administration of parathyroid hormone can serve as an indicator of tissue sensitivity to it.

The most important impact of parathyroid hormone on the kidney is its ability to reduce the reabsorption of phosphorus, increasing phosphaturia. The mechanism of diminution in different parts of the nephron is different: in the proximal part this parathyroid hormone effect is due to an increase in permeability and occurs with the participation of cAMP, in the distal part it does not depend on cAMP. The phosphaturic effect of parathyroid hormone changes with vitamin D deficiency, metabolic acidosis and a decrease in phosphorus content. Parathyroid hormones slightly increase the total tubular reabsorption of calcium. At the same time, it reduces it in the proximal and increases it in the distal parts. The latter has a dominant role - parathyroid hormone decreases calcium clearance. Parathyroid hormone decreases the tubular reabsorption of sodium and its bicarbonate, which explains the development of acidosis in hyperparathyroidism. It increases the formation of 1,25-dihydroxycholecalciferol 1,25 (OH ₂ ) D ₃ - the active form of vitamin D ₃ in the kidneys . This compound increases the reabsorption of calcium in the small intestine by stimulating the activity of a specific calcium binding protein (Ca-binding protein, CaBP) in its wall.

The normal level of parathyroid hormone averages 0.15-0.6 ng / ml. It varies depending on age and sex. The average content of parathyroid hormone in the blood of people aged 20-29 years (0.245 ± 0.017) ng / ml, 80-89 years - (0.545 ± 0.048) ng / ml; the level of parathyroid hormone in 70-year-old women - (0.728 ± 0.051) ng / ml, in men of the same age - (0.466 ± 0.40) ng / ml. Thus, the content of parathyroid hormone increases with age, but more so in women.

As a rule, several different tests should be used for the differential diagnosis of hypercalcemia.

We present the clinico-pathogenetic classification developed by us, based on the classification of OV Nikolaev and VN Tarkaeva (1974).

Clinico-pathogenetic classification of diseases associated with impaired secretion of parathyroid hormone and its sensitivity

Primary hyperparathyroidism

1. By pathogenesis:
   • hyperfunctioning adenoma (adenomas);
   • hyperplasia of OGRFA;
   • hyperfunctioning carcinoma of the parathyroid glands;
   • multiple endocrine neoplasia of type I with hyperparathyroidism (Vermeer's syndrome);
   • multiple endocrine neoplasia of type II with hyperparathyroidism (Sipple syndrome).
2. By clinical features:
   • Bone form:
     • osteoporotic,
     • fibro-cystic osteitis,
     • "Pagetoid";
   • visceropathic form:
     • with a primary lesion of the kidneys, the gastrointestinal tract, the neuropsychic sphere;
   • mixed form.
3. With the flow:
   • acute;
   • chronic.

Hyperparathyroidism secondary (secondary hyperfunction and hyperplasia of the parathyroid glands with prolonged hypocalcemia and hyperphosphataemia)

1.   Kidney pathology:
   • chronic renal failure;
   • tubulopathy (such as Albright-Fanconi);
   • renal rickets.
2.   Intestinal pathology:
   • syndrome of impaired intestinal absorption.
3. Bone pathology:
   • osteomalacia senile;
   • puerperal;
   • idiopathic;
   • Paget's disease.
4. Insufficiency of vitamin D:
   • kidney disease;
   • liver;
   • hereditary enzymopathies.
5. Malignant diseases: myeloma.

Hyperparathyroidism tertiary

1. Autonomously functioning adenoma (adenomas) of the parathyroid glands, developing against the background of a long-term secondary hyperparathyroidism.

Pseudohyperparathyroidism

1. Production of parathyroid hormone by tumors of nonparathyroid origin.

Hormonal-inactive cystic and tumor formations of the parathyroid glands

1. Cyst.
2. Hormonal-inactive tumors or carcinoma.

Hypoparathyroidism

1. Congenital maldevelopment or absence of parathyroid glands.
2. Idiopathic, autoimmune genesis.
3. Postoperative, developed in connection with the removal of parathyroid glands.
4. Postoperative due to impaired blood supply and innervation.
5. Radiation injuries, exogenous and endogenous (remote radiation therapy, treatment of the thyroid gland with radioactive iodine).
6. Damage to the parathyroid glands with hemorrhage, infarction.
7. Infectious damage.

Pseudohypoparathyroidism

• I type - insensitivity of target organs to parathyroid hormone, dependent on adenylate cyclase;
• Type II is the insensitivity of target organs to parathyroid hormone, independent of adenylate cyclase, possibly of autoimmune genesis.

Pseudo pseudohypyparatyreosis

The presence of somatic signs of pseudohypoparathyroidism in healthy relatives in families of patients with pseudohypoparathyroidism without characteristic biochemical disorders and without tetany.

[13], [14], [15], [16], [17], [18], [19], [20], [21]