Causes and pathogenesis of hypoparathyroidism

The following main etiological forms of hypoparathyroidism can be distinguished (in descending order of frequency): postoperative; associated with radiation, vascular, infectious damage to the parathyroid glands; idiopathic (with congenital underdevelopment, absence of parathyroid glands or autoimmune genesis).

The most common cause of hypoparathyroidism is the removal or damage of the parathyroid glands (one or more) during imperfect thyroid surgery, which is associated with their anatomical proximity, and in some cases - with the unusual location of the glands. Their injury during surgery, disruption of the innervation and blood supply to the parathyroid glands are important. The incidence of the disease after thyroid surgery varies, according to different authors, from 0.2 to 5.8%. Postoperative hypoparathyroidism is more often observed in patients who have undergone thyroid extirpation for malignant tumors. The development of the disease is typical after surgery on the parathyroid glands for hyperparathyroidism. In these cases, hypoparathyroidism is associated with the removal of the most active tissue with insufficient (suppressed) activity of the remaining parathyroid glands, with a sharp drop in hormonal activity and serum calcium levels, and with a decrease in the overall calcium resources in the body due to bone pathology.

Hypoparathyroidism can be caused by radiation damage to the parathyroid glands during external beam irradiation of the head and neck organs, as well as by endogenous irradiation during treatment of diffuse toxic goiter or thyroid cancer with radioactive iodine ( ¹³¹ 1).

The parathyroid glands can be damaged by infectious factors, inflammatory diseases of the thyroid gland and surrounding organs and tissues ( thyroiditis, abscesses, phlegmon of the neck and oral cavity), amyloidosis, candidiasis, hormonally inactive tumors of the parathyroid gland, and hemorrhages into a tumor of the parathyroid glands.

Latent hypoparathyroidism is detected against the background of provoking factors such as intercurrent infections, pregnancy, lactation, calcium and vitamin D deficiency in the diet, a shift in the acid-base balance towards alkalosis (with vomiting, diarrhea, hyperventilation), poisoning (chloroform, morphine; ergot, carbon monoxide).

Hypoparathyroidism of unclear genesis, called idiopathic, is also encountered. This group includes patients with developmental disorders of the 3rd-4th branchial arch (Di George syndrome), congenital dysplasia of the parathyroid glands, as well as autoimmune disorders causing isolated gland deficiency or multiple hormonal deficiency, including this disease. In the genesis of idiopathic hypoparathyroidism, the importance of genetic family factors, as well as some congenital metabolic disorders, is undoubtedly important. Relative parathyroid hormone deficiency may be associated with the secretion of parathyroid hormone with reduced biological activity or insensitivity of target tissues to its action. Hypoparathyroidism may be observed in children whose mothers suffer from hypomagnesemia and hypoparathyroidism.

In the pathogenesis of the disease, the main role is played by absolute or relative deficiency of parathyroid hormone with hyperphosphatemia and hypocalcemia, the development of which is associated with impaired calcium absorption in the intestine, decreased mobilization from bones and a relative decrease in its tubular reabsorption in the kidneys. Deficiency of parathyroid hormone leads to a decrease in the level of calcium in the blood both independently and indirectly, due to a decrease in the synthesis of the active form of vitamin D ₃ - l,25 (OH ₂ ) D ₃ (cholecalciferol) in the kidneys.

Negative calcium and positive phosphorus balance disrupt the electrolyte balance, changing the calcium/phosphorus and sodium/potassium ratios. This leads to a universal disruption of the permeability of cell membranes, in particular in nerve cells, to a change in the polarization processes in the synapse area. The resulting increase in neuromuscular excitability and general autonomic reactivity leads to an increase in convulsive readiness and tetanic crises. In the genesis of tetany, a significant role belongs to the disruption of magnesium metabolism and the development of hypomagnesemia. This promotes the penetration of sodium ions into the cell and the exit of potassium ions from the cell, which also promotes an increase in neuromuscular excitability. The resulting shift in the acid-base state towards alkalosis has the same effect.

Pathological anatomy

The anatomical substrate of hypoparathyroidism is the absence of parathyroid glands (congenital or due to surgical removal), underdevelopment and atrophic processes due to autoimmune damage, impaired blood supply or innervation, radiation or toxic effects. In the internal organs and walls of large vessels, calcium salts may be deposited with hypoparathyroidism.