Diagnosis of hypoparathyroidism

Diagnosis of overt forms of hypoparathyroidism is not difficult. It is based on the anamnesis data (surgery on the thyroid or parathyroid glands, treatment with ¹³¹ 1); the presence of increased neuromuscular excitability with attacks of tonic convulsions or readiness for convulsions; the presence of hypocalcemia and hypocalciuria; hyperphosphatemia and hypophosphatemia; a decrease in the level of serum parathyroid hormone; a decrease in the excretion of cAMP in the urine, reaching normal values after the administration of parathyroid hormone preparations; the presence of prolongation of the QT and ST intervals on the ECG; in later stages of the disease - the presence of cataracts and other manifestations of tissue calcification; changes in ectodermal derivatives - skin, hair, nails, tooth enamel.

In hypoparathyroidism, the total calcium content in the blood drops below 2.25 mmol/l; at a level of less than 4.75 mmol/l, calcium ceases to be detected in the urine (in the Sulkovich test). Hyperparathyroid crises occur when the calcium level in the blood serum is less than 1.9-2 mmol/l, and ionized calcium is less than 1-1.1 mmol/l.

To detect latent parathyroid gland insufficiency, tests are used that characterize the increase in mechanical and electrical excitability of the neuromuscular apparatus. With their help, the following symptoms are detected.

Chvostek's symptom is a contraction of the facial muscles when tapping at the site of the facial nerve exit in front of the external auditory canal. There are Chvostek's symptom of the first degree, when all the facial muscles on the side of the tapping contract; of the second degree - the muscles in the area of the wings of the nose and the corner of the mouth contract; of the third degree - only in the area of the corner of the mouth. It should be remembered that this symptom is non-specific. It can be positive in neuroses and hysteria.

Trousseau's symptom - cramps in the area of the hand ("obstetrician's hand", "writing hand") 2-3 minutes after tightening the shoulder with a tourniquet or cuff of a blood pressure measuring device.

Weiss's sign - contraction of the round muscle of the eyelids and the frontal muscle when tapping at the outer edge of the orbit.

Hoffman's symptom is the appearance of paresthesia when pressing in the areas of nerve branching.

Schlesinger's symptom - cramps in the extensor muscles of the thigh and foot during rapid passive flexion of the leg at the hip joint with the knee joint straightened.

Erb's symptom is increased electrical excitability of the nerves of the extremities when stimulated by a weak galvanic current (less than 0.5 mA).

The hyperventilation test causes an increase in convulsive readiness or the development of an attack of tetany with deep forced breathing.

It should be remembered that all these tests are non-specific and do not reveal hypoparathyroidism as such, but increased convulsive readiness. In the presence of a convulsive symptom complex, differential diagnostics with diseases accompanied by convulsions and hypocalcemia is required.

According to the modified classification of Klotz (1958), tetany can be divided according to clinical and etiopathogenetic features as follows.

1. Symptomatic (about 20% of all cases):
   • hypocalcemic, with insufficient mobilization of calcium (hypoparathyroidism, pseudohypoparathyroidism); with incomplete absorption (malabsorption syndrome, diarrhea) or loss of calcium (rickets, hypovitaminosis D, osteomalacia, lactation); with increased need for calcium (pregnancy); chronic renal failure (insufficient synthesis of l,25(OH)2D3 _; hyperphosphatemia);
   • in alkalosis (hyperventilation, gastrogenic - in case of vomiting, hypokalemic in case of hyperaldosteronism);
   • in case of organic lesions of the central nervous system (vascular lesions, encephalopathy, meningitis).
2. Spasmophilia (about 80% of all cases) is a hereditary disease that worsens in the presence of “tetanogenic” factors ( hypocalcemia, alkalosis).

In addition to the metabolic tetany discussed in the classification given, hypoparathyroidism must be differentiated from hypomagnesemia and from convulsive manifestations in hypoglycemia. Convulsions of non-metabolic origin must be differentiated from genuine epilepsy as such, tetanus, rabies, poisonings and intoxications.

Unlike hypoparathyroidism and pseudohypoparathyroidism, in most types of tetany (except for renal and intestinal forms) there are no disturbances in phosphorus-calcium metabolism.

Hypoparathyroidism can be a component of multiple endocrine deficiency syndrome of autoimmune genesis in combination with candidiasis, the so-called MEDAC syndrome (Multiple Endocrine Deficiency Autoimmune Candidiasis) - a genetic autosomal recessive syndrome with a picture of insufficiency of the parathyroid glands, adrenal cortex and fungal lesions of the skin and mucous membranes, with frequent (50% of cases) development of keratoconjunctivitis.

Pseudohypoparathyroidism and pseudopseudohypoparathyroidism are a group of rare hereditary syndromes with clinical and laboratory signs of parathyroid gland insufficiency (tetany, hypocalcemia, hyperphosphatemia) with elevated or normal levels of parathyroid hormone in the blood, short stature, skeletal developmental features (osteodystrophy, shortening of tubular bones of the extremities, defects of the dental system), metastatic calcification of soft tissues, and mental disorders. Pseudohypoparathyroidism was first described in 1942 by F. Albright et al. (synonyms: F. Albright's hereditary osteodystrophy, Albright-Bantam syndrome). The development of the disease is associated with tissue refractoriness (kidneys and bones) to endogenous and exogenous parathyroid hormone with its elevated or normal secretion and hyperplasia of the parathyroid glands. In 1980, P. Papapoulos et al. established that tissue insensitivity to parathyroid hormone depends on a decrease in the activity of a special protein, the so-called guanine-nucleotide-binding regulatory protein (GN, G, N), which ensures interaction between the receptor and the membrane of adenylate cyclase and participates in the activation and implementation of the functions of this enzyme. In this case, the synthesis of cAMP is disrupted. Pseudohypoparathyroidism type I was identified, in which the activity of GN protein is reduced by 40-50%. In such patients, the violation of hormonal sensitivity is not limited to parathyroid hormone alone, but also extends to other hormones dependent on the adenylate cyclase system, in particular, insensitivity of the thyroid gland to TSH with an increase in the reaction of TSH to TRH; resistance of the sex glands to LH and FSH with an increase in the reaction of these hormones to LH-RH in the absence of clinical signs of primary hypothyroidism and hypogonadism. In pseudohypoparathyroidism, apparently, part of the immunoreactive parathyroid hormone does not have biological activity. There is no data on the formation of antibodies to parathyroid hormone.

_{In the pathogenesis of pseudohypoparathyroidism type I,} a certain role is played by the deficiency of endogenous 1,25(OH) _2D3 due to impaired sensitivity to PTH and cAMP deficiency. With the introduction of dibutyryl-3',5'-cAMP, the content of 1,25(OH) _2D3 in the blood increases, and as a result of treatment with vitamin D3 preparations _, tissue sensitivity to parathyroid hormone increases, normocalcemia is maintained, tetany is eliminated, and correction of bone disorders is enhanced.

In pseudohypoparathyroidism type II, receptor sensitivity to parathyroid hormone is not impaired. GN protein activity is normal, parathyroid hormone can stimulate membrane adenylate cyclase, but it is assumed that the ability of calcium and phosphorus transport systems to respond to normally formed cAMP is impaired. It has been suggested that in pseudohypoparathyroidism type II, autoantibodies to the plasma membranes of renal tubular cells exist that block induced PTH-phosphaturia, i.e., autoimmune genesis of pseudohypoparathyroidism type II is assumed. In this form of the disease, the impairment of hormonal sensitivity is limited to tissues that respond to parathyroid hormone. No other impairments in this regard are observed.

With pseudohypoparathyroidism, various combinations of changes with varying degrees of their severity may occur, which is determined genetically. Relatives of patients with pseudohypoparathyroidism often have deviations from the norm of general development and skeletal defects without a violation of parathyroid hormone secretion, without pathology of phosphorus-calcium metabolism and seizures. This is the so-called pseudo-pseudohypoparathyroidism - a metabolically normal variant of pseudohypoparathyroidism. Due to the rarity of the pathology, the type of inheritance of this disease has not been precisely established. The ratio of its frequency in women and men is 1:1. They assume an X-linked dominant inheritance of two interrelated disorders - pseudo- and pseudopseudohypoparathyroidism, but there are cases of direct transmission of pseudohypoparathyroidism from father to son, which indicates the possibility of autosomal inheritance.

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