Syndrome of inadequate vasopressin production

Excessive production of vasopressin can be adequate, i.e. arise as a result of the physiological reaction of the posterior pituitary gland in response to appropriate stimuli (blood loss, taking diuretics, hypovolemia, hypotension, etc.), and inadequate.

Adequate hypersecretion of vasopressin has no independent clinical significance and is aimed at maintaining water-salt homeostasis in case of its disturbances.

Causes of inadequate vasopressin production syndrome.

Inadequate hypersecretion of vasopressin, independent of physiological regulation factors, as the primary cause of an independent clinical syndrome with a number of specific features was described by W. B. Schwartz and F. Bartter in 1967. However, as early as 1933, Parkhon reported a rare clinical syndrome with symptoms opposite to diabetes insipidus ("antidiabetes insipidus", "hyperhydropexic syndrome") and associated it with a primary excess of antidiuretic hormone (ADH). In Parkhon's description, 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 vasopressin production (SIVP), a frequent (but not absolute) coincidence in two symptoms is revealed: urinary retention and lack of thirst.

The syndrome of inappropriate vasopressin production may be caused by pathology of the neurohypophysis or be ectopic. The cause of vasopressor hyperactivity of the pituitary gland itself is largely unclear. It is observed in pulmonary diseases, including tuberculosis, in various CNS lesions, injuries, in particular head injuries, acute intermittent porphyria, psychoses, the syndrome of inappropriate vasopressin production is caused by a number of medicinal and toxic substances: vincristine, dichlorvos, chlorpropamide, nicotine, tegretol, etc.

The syndrome of inappropriate vasopressin production may complicate the course of myxedema, chronic adrenal insufficiency, panhypopituitarism. Ectopic inappropriate vasopressin production is associated with oncological diseases, mainly with small-cell bronchogenic carcinomas, and much less often with tuberculosis. For practical purposes, it is possible to conditionally distinguish idiopathic inappropriate vasopressin production originating from the pituitary gland, which, obviously, determines the pathological basis of Parhon's syndrome. The disease may be preceded by influenza, neuroinfections, pregnancy, childbirth, abortion, overheating in the sun, various psychotraumatic situations, etc.

Hyperproduction of vasopressin leads to water retention, decreased plasma osmolarity, renal loss of sodium, and hyponatremia. However, low plasma sodium levels and hypervolemia do not cause a compensatory, adequate decrease in vasopressin. Hypervolemia suppresses aldosterone production, thereby aggravating sodium loss. It is possible that natriuresis is also enhanced by activation of the atrial natriuretic factor under conditions of hypervolemia. Thus, the pathophysiological basis of the syndrome of inappropriate vasopressin production is: loss of sodium with urine; hyponatremia, suppressing the thirst center; hypervolemia, leading to water intoxication.

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Pathogenesis

Morphological changes in the hypothalamus and neurohypophysis have been studied very little. In the cases studied, changes are rarely detected, mainly at the level of subcellular structures, indicating an increase in the functional activity of neurons in the supraoptic and paraventricular nuclei. In the pituicytes of the posterior lobe of the pituitary gland, signs of hormone deposition are observed, such as cell hypertrophy.

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Symptoms of inadequate vasopressin production syndrome.

The main complaints of patients are insufficient urination (oliguria) and weight gain. Peripheral edema may not be pronounced due to sodium loss, and a positive water balance causes hypervolemia and water intoxication syndromes: headaches, dizziness, anorexia, nausea, vomiting, sleep disorders. Symptoms of water intoxication appear after the sodium level in the plasma decreases below 120 mmol/l. With severe hyponatremia (100-110 mmol/l), symptoms of CNS damage come to the fore - disorientation, convulsions, arrhythmia and coma.

Idiopathic inadequate production of vasopressin (Parchon syndrome) may occur with constant oliguria or with paroxysmal, periodic oliguria. Periods of fluid retention (urine volume 100-300 ml/day) lasting 5-10 days are replaced by spontaneous diuresis, sometimes up to 10 l/day. During oliguria, diarrhea sometimes occurs, somewhat reducing the accumulation of fluid in the body. During polyuria - severe general weakness, nausea, vomiting, chills, convulsions, hypotension, arrhythmia, i.e. symptoms of dehydration.

Diagnostics of inadequate vasopressin production syndrome.

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

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

Hypothyroidism (which itself can induce inadequate production of vasopressin) is characterized by a decrease in plasma levels of T3, T4 and an increase in TSH, and if they cannot be quickly determined, the lack of effect from thyroid drug therapy may be decisive in differential diagnosis .

The greatest difficulties in differential diagnosis arise in connection with idiopathic edema syndrome - a disease that has many clinically similar symptoms, but a different pathophysiological nature. Idiopathic edema syndrome occurs mainly in women aged 20-50. 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 only small local edema is observed, often of the face.

Quite often, only premenstrual cyclic edema is observed. Many patients have an orthostatic nature, a clear connection with emotional stress ("emotional", "mental edema"). One or another degree of emotional and personal disorders is observed in all patients, in some cases hypochondriacal and asthenic manifestations, schizoid and psychasthenic features are noted. Such hysterical symptoms as "lump in the throat", transient loss of voice and vision are characteristic. A number of vegetative changes: impaired thermoregulation, lability of pulse and blood pressure, numbness of the extremities, migraines, fainting, sometimes increased appetite and a tendency to obesity. Thirst is a common symptom in idiopathic edema. In women, anovulatory disorders of the menstrual cycle are often detected.

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

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Treatment of inadequate vasopressin production syndrome.

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

The idiopathic form of inadequate vasopressin production is difficult to treat, since there are currently no specific agents that block the synthesis of vasopressin in the pituitary gland. There are isolated observations of the beneficial effect of parlodel in both inadequate vasopressin production and idiopathic edema syndrome. The mechanism of the diuretic effect of this drug is presumably associated with increased dopamine activity, which increases renal hemodynamics and/or reduces the potentiating effect of prolactin on ADH. The foreign literature reports on the drug demeclocycline, which blocks the effect of vasopressin on the kidneys and causes nephrogenic diabetes.

Prevention

The polyetiology of the syndrome makes its prevention difficult, but low fluid intake is a common factor that inhibits the appearance of clinical symptoms.

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Forecast

Generally favorable, but depends on the nature of the underlying disease and the cause of the syndrome of inappropriate vasopressin production. Severe forms of idiopathic inappropriate vasopressin production can be fatal due to severe water intoxication.

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