Diagnosis of hypoparathyroidism

Diagnosis of manifest forms of hypoparathyroidism is not difficult. It is based on anamnesis data (surgery on the thyroid or parathyroid gland, treatment ¹³¹ 1); the presence of increased neuromuscular excitability with attacks of tonic convulsions or readiness for convulsions; presence of hypocalcemia and hypocalciuria; hyperphosphatemia and hypophosphaturia; decreased serum parathyroid hormone levels; on a decrease in the excretion of cAMP in the urine, which reaches its normal value after the administration of parathyroid hormone preparations; on the presence of an extension of the intervals QT and ST on the ECG; in later stages of the disease - on the presence of cataracts and other manifestations of calcification of tissues; on the changes of ectodermal derivatives - skin, hair, nails, enamel of teeth.

With hypoparathyroidism, the total blood calcium content decreases below 2.25 mmol / l, at a level of less than 4.75 mmol / l, calcium ceases to be detected in the urine (in Sulkovich's sample). Hyperparathyroid crises occur at a serum calcium level of less than 1.9-2 mmol / L, and ionized - less than 1-1.1 mmol / l.

To reveal the latent deficiency of the parathyroid glands, samples characterizing the increase in the mechanical and electrical excitability of the neuromuscular apparatus are used. With their help, the following symptoms are identified.

The symptom of the tail is the contraction of the facial muscles when tapping at the exit of the facial nerve in front of the external auditory canal. Distinguish the symptom of Khvostek I degree, when all the facial muscles contract on the side of tapping; II degree - muscles contract in the region of the wings of the nose and the corner of the mouth; III degree - only in the angle of the mouth. It should be remembered about the nonspecificity of this symptom. It can be positive for neuroses and hysteria.

The Trusso symptom is convulsions in the hand area ("hand of an obstetrician", "writing hand") 2-3 minutes after the shoulder is pulled over by a tourniquet or cuff of a device for measuring blood pressure.

The symptom of Weiss is the contraction of the round muscle of the eyelids and the frontal muscle at the effleurage at the outer edge of the orbit.

The symptom of Hoffmann is the appearance of paresthesia when pressure is applied in the branches of the branching of the nerves.

Symptom Schlesinger - cramps in the extensor muscles of the thigh and foot with a rapid passive flexion of the leg in the hip joint with a straightened knee joint.

The Erb symptom is an increased electroexcitability of the nerves of the extremities when stimulated by a weak galvanic current (less than 0.5 mA).

A test with hyperventilation is the cause of increased convulsive readiness or development of an attack of tetany with deep forced breathing.

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

According to the modified Klotz classification (1958), according to the clinical and etiopathogenetic signs of tetany, it can be divided 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) 2D ₃; hyperphosphataemia);
   • with alkalosis (hyperventilation, gastrogenic - with vomiting, hypokalemic in hyperaldosteronism);
   • with organic lesions of the central nervous system (vascular lesions, encephalopathies, meningitis).
2. Spasmophilia (about 80% of all cases) is a hereditary disease, aggravated in the presence of "tetanogenic" factors ( hypocalcemia, alkalosis).

In addition to the metabolic tetany, referred to in the cited classification, hypoparathyroidism must be differentiated from hypomagnesemia and from convulsive manifestations in hypoglycemia. From convulsive seizures of non-metabolic origin it is necessary to distinguish genuine epilepsy as such, tetanus, rabies, poisoning and intoxication.

In contrast to hypoparathyroidism and pseudohypoparathyroidism, in most types of tetany (with the exception of renal and intestinal forms), there are no violations of phosphorus-calcium metabolism.

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

Pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism are a group of rare hereditary syndromes with clinical and laboratory signs of parathyroid gland failure (tetany, hypocalcaemia, hyperphosphataemia) with increased or normal parathyroid hormone content, with short stature, skeletal development (osteodystrophy, truncation of limb bones, dentition defects) , with metastatic calcification of soft tissues, mental disorders. Pseudohypoparathyroidism was first described in 1942. F. Albright et al. (synonyms: hereditary osteodystrophy F. Albright, Albright-Bantam syndrome). The development of the disease is associated with the refractoriness of tissues (kidneys and bones) to the endogenous and exogenous parathyroid hormone with increased or normal secretion and hyperplasia of the parathyroid glands. In 1980, P. Papapoulos et al. It was found that the tissue insensitivity to parathyroid hormone depends on the decrease in the activity of a specific protein, the so-called guanine nucleotide-binding regulatory protein (GN, G, N), which provides the interaction between the receptor and adenylate cyclase membrane and is involved in the activation and realization of the functions of this enzyme. This breaks down the synthesis of cAMP. Type I pseudohypoparathyroidism is distinguished, in which the activity of the GN protein is reduced by 40-50%. In such patients, the violation of hormonal sensitivity is not limited only to the parathyroid hormone, but extends to other hormones dependent on the adenylate cyclase system, in particular, the thyroid insensitivity to TSH can be observed with an increase in the TSH response to TRH; the resistance of the gonads to LH and FSH with an increase in the reaction of these hormones to LH-RG 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 are no data on the formation of antibodies to parathyroid hormone.

In the pathogenesis of type I pseudohypo- parathyroidism, the endogenous deficiency of 1,25 (OH) ₂ D ₃ plays a role in connection with impaired sensitivity to PTH and cAMP deficiency. When dibutyryl-3 ', 5'-cAMP is administered, the blood content of 1,25 (OH) ₂ D3 is increased , and as a result of treatment with vitamin D ₃ preparations, tissue sensitivity to parathyroid hormone increases, normocalcemia is maintained, tetany is eliminated and bone injury correction is enhanced.

In pseudohypoparathyroidism of type II, the receptor sensitivity to parathyroid hormone is not impaired. The activity of the GN protein is normal, the parathyroid hormone can stimulate the membrane adenylate cyclase, but it is assumed that the ability of the calcium and phosphorus transport systems to react to the normally formed cAMP is impaired. An opinion was expressed on the existence of type II autoantibodies to pseudohypoparathyroid cells in the renal tubules, which block the inducible PTH-phosphaturia, ie, autoimmune genesis of type II pseudohypo- parathyreosis is assumed. With this form of the disease, the violation of hormonal sensitivity is limited by tissues that react to parathyroid hormone. There are no other violations in this regard.

With pseudohypoparathyroidism, there can be different combinations of changes with different degrees of their severity, which is determined genetically. In relatives of patients with pseudohypoparathyroidism, there are often deviations from the norm of general development and defects of the skeleton without disturbing the secretion of parathyroid hormone, without the 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 pathology, the type of inheritance of this disease is not precisely established. The ratio of its frequency in women and men is 1: 1. Assume the dominant inheritance of two interrelated disorders - pseudo and pseudo pseudohypoparathyroidism - associated with the X chromosome, but there are cases of direct transmission of pseudohypoparathyroidism from father to son, which indicates the possibility of autosomal inheritance.

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