Syndrome of inadequate production of vasopressin

Excessive production of vasopressin may be adequate, ie, it occurs as a result of the physiological response of the posterior lobe of the pituitary gland in response to appropriate stimuli (blood loss, diuretics, hypovolemia, hypotension, etc.), and inadequate.

Adequate hypersecretion of vasopressin has no independent clinical significance and is aimed at preserving water-salt homeostasis when it is disturbed.

Causes of the the syndrome of inadequate production is repressed

Inadequate, independent of the factors of physiological regulation, hypersecretion of vasopressin as the root cause of an independent clinical syndrome with a number of specific features, was described by W. V. Schwartz and F. Bartter in 1967. However, as early as 1933, Parkhon reported a rare clinical syndrome, according to the symptoms opposite to diabetes insipidus ("insipid antidiabet", "hyperhydropsy syndrome"), and linked it to the primary excess of antidiuretic hormone (ADH). In the description of Parhon, the disease was characterized by oliguria, lack of thirst and the appearance of edema. As a result of comparing the clinical symptoms of Parkhon's syndrome and the syndrome of inappropriate production of vasopressin (SNPV), a frequent (but not absolute) coincidence in two symptoms: delay in urination and absence of thirst.

The syndrome of inadequate production of vasopressin may be due to the pathology of the neurohypophysis or to be ectopic. The cause of the vasopressor hyperactivity of the pituitary itself is largely unclear. It is observed in pulmonary diseases, including tuberculosis, with various lesions of the central nervous system, traumas, in particular the head, acute intermittent porphyria, psychosis, the syndrome of inappropriate production of vasopressin causes a number of medicinal and toxic substances: vincristine, dichlorvos, chlorpropamide, nicotine, tegretol and other

The syndrome of inadequate production of vasopressin can complicate the course of myxedema, chronic adrenal insufficiency, panhypopituitarism. Ectopic inappropriate production of vasopressin is associated with cancer, mainly with small-cell bronchogenic carcinomas, and is much less common with tuberculosis. For practical purposes, it can be conditionally identified and idiopathic inadequate production of vasopressin, emanating from the pituitary gland, which, apparently, determines the pathological basis of Parkhon syndrome. The disease can be preceded by influenza, neuroinfections, pregnancy, childbirth, abortion, overheating in the sun, various psychotrauma situations, etc.

Hyperproduction of vasopressin leads to water retention, decreased plasma osmolality, renal sodium loss, and hyponatremia. However, low sodium in the plasma and hypervolemia do not cause compensatory, adequate reduction of vasopressin. Hypervolaemia suppresses the production of aldosterone, thereby aggravating the loss of sodium. It is possible that natriuresis is also intensified by activation in the conditions of hypervolemia of the atrial natriuretic factor. Thus, the pathophysiological basis of the syndrome of inadequate production of vasopressin is: loss of sodium in the urine; hyponatremia, the overwhelming center of thirst; hypervolemia leading to water intoxication.

[1], [2], [3], [4]

Pathogenesis

Morphological changes in the hypothalamus and neurohypophysis have been studied extremely little. In the cases studied, changes are rarely detected, mainly at the level of subcellular structures, which indicate an increase in the functional activity of neurons of supraoptic and paraventricular nuclei. In the pituitary cells of the posterior lobe of the pituitary gland, there are signs of hormone deposition, for example, cell hypertrophy.

[5], [6], [7], [8], [9], [10], [11]

Symptoms of the the syndrome of inadequate production is repressed

The main complaints of patients - on insufficient urination (oliguria) and weight gain. Peripheral edema may not be expressed due to loss of sodium, and a positive water balance causes hypervolemia and syndromes of water intoxication: headaches, dizziness, anorexia, nausea, vomiting, sleep disturbances. Symptoms of water intoxication appear after lowering the sodium level in the plasma below 120 mmol / l. With severe hyponatremia (100-110 mmol / l), the symptoms of central nervous system lesions come to the forefront - disorientation, convulsions, arrhythmia and coma.

Idiopathic inadequate production of vasopressin (Parkhon syndrome) can occur with a permanent oliguria or with paroxysmal, periodic. The periods of fluid retention (the amount of urine 100-300 ml / day) lasting 5-10 days are followed by spontaneous diuresis, sometimes up to 10 liters / day. During oliguria, diarrhea sometimes occurs, which somewhat reduces the accumulation of fluid in the body. In the period of polyuria - a sharp general weakness, nausea, vomiting, chills, convulsions, hypotension,  arrhythmia, ie, symptoms of dehydration.

Diagnostics of the the syndrome of inadequate production is repressed

The diagnosis is not complicated if there is a specific cause-inadequate production of vasopressin and is based on history, clinical symptoms and laboratory examination-hyponatremia, natriuria, hypervolemia, hypoaldosteronemia.

Primary differentiation is based on the exclusion of pathology of the liver, kidneys, heart, adrenal insufficiency, hypothyroidism. The difficulty of differential diagnostics lies in the fact that such basic cardinal signs as hyponatremia and low aldosterone levels may not be expressed due to uncontrolled admission of patients with diuretics causing secondary aldosteronism, leveling sodium loss and eliminating hypovolemia. The same mechanism leads to the development of thirst.

For  hypothyroidism  (which itself can induce inadequate production of vasopressin), a decrease in the blood levels of T3, T4 and an increase in TSH is characteristic, and if it is impossible to determine them quickly, the absence of the effect of thyroid therapy can be decisive in differential diagnosis.

The greatest difficulties of differential diagnosis arise in connection with the syndrome of idiopathic edema - a disease that has many clinically similar symptoms, but a different pathophysiological nature. Syndrome of idiopathic edema occurs mainly in women 20-50 years old. Its pathogenesis is associated with a number of neurogenic, hemodynamic and hormonal disorders leading to dysregulation of water-salt homeostasis. This syndrome is characterized by the development of peripheral and ubiquitous edema, in mild cases there are only small local edema, often the face.

Often observed only premenstrual cyclic edema. Many patients noted their orthostatic character, a clear connection with emotional stress ("emotional", "mental edema"). This or that degree of emotional and personality disorders is observed in all patients, in some cases hypochondriacal and asthenic manifestations, schizoid and psychasthenic traits are noted. Characteristic of such hysterical symptoms as "lump in the throat", transient loss of voice and vision. A number of vegetative changes: violation of thermoregulation, lability of pulse and arterial pressure, numbness of limbs, migraines, fainting, sometimes increased appetite and a tendency to obesity. Thirst is a common symptom in idiopathic edema. Women often have anovulatory disorders of the menstrual cycle.

Vasopressin is elevated in all patients with the syndrome of inappropriate vasopressin production, including Parkhon syndrome, but not always with idiopathic edema. Aldosterone is reduced in the syndrome of inadequate production of vasopressin and is elevated in a significant majority of patients with idiopathic edema. That is why such edemas are often considered as a variant of secondary, often orthostatic, aldosteronism and vasopressinism. Hyponatremia and hypervolemia, characteristic of inadequate production of vasopressin, are never observed with idiopathic edema.

[12], [13], [14]

Treatment of the the syndrome of inadequate production is repressed

Induced inadequate production of vasopressin is corrected by treatment of the underlying disease. By analogy with the fact that compensation of water losses is the first link in the treatment of diabetes insipidus, with the syndrome of inadequate production of vasopressin, regardless of its etiology, treatment begins with a decrease in fluid intake within 800-1000 ml / day. Restricted drinking regimen leads to the elimination of hypervolemia, a reduction in sodium naresis and an increase in the concentration of sodium in the blood. In case of inadequate production of vasopressin, in contrast to idiopathic edema syndrome, salt intake should not be limited.

The idiopathic form of inadequate production of vasopressin is difficult for therapy, since there are currently no specific drugs blocking the synthesis of vasopressin in the pituitary gland. There are single observations on the beneficial effects of the parlodel and in the inadequate production of vasopressin, and in the syndrome of idiopathic edema. The mechanism of the diuretic effect of this drug is presumably associated with an increase in the activity of dopamine, which increases renal hemodynamics and / or reduces the potentiating effect of prolactin on ADH. In foreign literature, a preparation of demeclocicline that blocks the effect of vasopressin on the kidneys and causes nephrogenic diabetes is reported.

Prevention

The polyethiologic nature of the syndrome makes it difficult to prevent, but low fluid intake is a common factor that inhibits the emergence of clinical symptoms.

[15], [16]

Forecast

In general, it is favorable, but depends on the nature of the underlying disease and the cause that caused the syndrome of inadequate production of vasopressin. Severe forms of idiopathic inadequate production of vasopressin can lead to death as a result of severe water intoxication.

[17], [18], [19], [20]