Hypoaldosteronism

Hypoaldosteronism is one of the least studied issues of clinical endocrinology. Information about this disease is absent in both manuals and textbooks of endocrinology, despite the fact that isolated hypoaldosteronism as an independent clinical syndrome was described more than 30 years ago.

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Pathogenesis

There are a number of hypotheses about the nature of isolated hypoaldosteronism, the pathogenesis of which may be associated with a defect in the biosynthesis of aldosterone (primary isolated hypoaldosteronism) or with a violation of individual links in its regulation (secondary isolated hypoaldosteronism).

Primary isolated hypoaldosteronism is most likely caused by a deficiency of two enzyme systems that control aldosterone synthesis at the last stages: 18-hydroxylase (blocks the conversion of corticosterone to 18-hydroxycorticosterone, type I) and/or 18-dehydrogenase (blocks the conversion of 18-hydroxycorticosterone to aldosterone, type II). This biosynthesis disorder is often congenital, manifesting itself in infants or early childhood. Symptoms are characterized by varying degrees of salt loss, sometimes growth disturbances, and the absence of sexual dysfunction. Salt loss and vascular hypotension increase aldosterone-renin production (hyperreninemic hypoaldosteronism). Stimulating factors (orthostasis, diuretics, etc.) slightly increase aldosterone production. With age, this form tends to spontaneous remission.

A similar clinical syndrome with generalized or partial enzyme deficiency may be acquired and observed in adolescence and adults. There are observations in which acquired 18-dehydrogenase deficiency with clinical manifestations of isolated hypoaldosteronism is combined with polyendocrine autoimmune deficiency, including Hashimoto's goiter, idiopathic hypoparathyroidism.

The defect of aldosterone biosynthesis can be induced by a number of pharmacological agents with their long-term use: heparin, indomethacin, licorice preparations containing DOC-like substances, beta-blockers, veroshpiron. In this case, the action of the latter directly on the glomerular zone as a result of increased sodium excretion can overlap its stimulating renin-angiotensin effect. Pharmacological adrenalectomy of a wide spectrum is caused by elepten, chloditan, metopirone.

In addition to primary isolated hypoaldosteronism, secondary hypoaldosteronism is observed, associated with insufficient renin production by the kidneys or the release of inactive renin (hyporeninemic hypoaldosteronism). In this form, ARP and aldosterone production are weakly stimulated by orthostatic load, sodium restriction in the diet, diuretics, and even ACTH.

This group is also heterogeneous in pathogenesis and, along with independent clinical variants, hyporeninemic hypoaldosteronism often accompanies and complicates the course of such diseases as diabetes mellitus, chronic nephritis with renal tubular acidosis and moderate renal dysfunction, in particular, decreased creatinine clearance. Universal vascular lesions, including those of the kidneys, as well as ketoacidosis in patients with diabetes mellitus create a number of prerequisites for the development of hypoaldosteronism. The most important of them are: production of inactive renin, insulin deficiency, which indirectly affects the synthesis of aldosterone; decreased adrenergic activity and prostaglandins E1 and E2, which stimulate ARP. Impaired autonomic regulation with low adrenergic activity underlies hyporeninemic hypoaldosteronism in Parkinson's disease and orthostatic hypotension syndrome.

Hypoaldosteronism induced by a long-standing decrease in ARP may develop after removal of an aldosteronoma from one of the adrenal glands as a result of atrophy of the zona glomerulosa of the other. Having arisen soon after the operation, characteristic periodic attacks of hypoaldosteronism gradually weaken and disappear as ARP increases and the zona glomerulosa is restored.

Hypoaldosteronism in combination with insufficient cortisol production is observed in Addison's disease, after bilateral adrenalectomy, and in congenital disorders of corticosteroid biosynthesis in patients with adrenogenital syndrome.

Aldosterone deficiency promotes increased reabsorption, decreased secretion and excretion of potassium in the renal tubules. Its retention, usually prevailing over the loss of sodium, leads to universal hyperkalemia. Hyperkalemic hyperchloremic renal tubular acidosis reduces the production and excretion of ammonium and increases the tendency to azotemia, especially in primary kidney damage in patients with diabetes mellitus. The severity of metabolic disorders determines the clinical symptoms of primary hyperaldosteronism and its severity.

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Symptoms hypoaldosteronism

Isolated hyporeninemic hypoaldosteronism as an independent clinical syndrome was first described by R. V. Hudson et al. This is a rare disease observed mainly in men. It is characterized by general and muscle weakness, hypotension, dizziness, a tendency to faint, bradycardia, sometimes reaching the degree of atrioventricular block, respiratory rhythm disturbances, up to Adams-Stokes attacks with clouding of consciousness and convulsions. The course of the disease is chronic and wave-like. Periods of exacerbation with circulatory collapse alternate with spontaneous remissions. It is assumed that the possibility of unexpected improvements and a long-term "erased" course, distinguished only by a tendency to orthostatic hypotension, is determined by a compensatory increase in the production of glucocorticoids and catecholamines, partially and temporarily replenishing the aldosterone deficiency.

In cases where, in chronic adrenal insufficiency ( Addison's disease, condition after bilateral adrenalectomy), electrolyte disturbances are more pronounced (hyperkalemia, convulsions, paresthesia, decreased renal filtration), one should think about the predominance of mineralocorticoid deficiency over glucocorticoid deficiency.

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Forms

Aldosterone deficiency in the body can be:

• isolated;
• be combined with a deficiency of other corticosteroids;
• caused by a decrease in the receptor sensitivity of effector organs to the action of aldosterone, the synthesis of which is not impaired (pseudohypoaldosteronism).

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Diagnostics hypoaldosteronism

Laboratory diagnostics are based on low aldosterone levels, hyperkalemia (6-8 mEq/L), sometimes hyponatremia, increased sodium/potassium ratio in urine and saliva, normal or elevated levels of cortisol, 17-hydroxycorticosteroids and catecholamines in blood and urine. ARP depends on the form of the disease; pseudohypoaldosteronism is characterized by high levels of both aldosterone and ARP. ECG shows signs of hyperkalemia: prolongation of the PQ interval, bradycardia, varying degrees of transverse block, and a high peaked wave in the chest leads. It should be emphasized that hyperkalemic syndrome with a complex of cardiovascular disorders and orthostatic hypotension of unknown genesis require close attention from both therapists and endocrinologists.

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Differential diagnosis

Differential diagnostics of isolated hypoaldosteronism as an independent clinical syndrome is carried out with hypoaldosteronism developed against the background of diabetes mellitus and chronic nephritis, congenital hyperplasia of the adrenal cortex with a defect of 11-hydroxylase; with orthostatic hypotension syndrome based on damage to the autonomic nervous system; with hypoaldosteronism in withdrawal syndrome after long-term use of mineralocorticoids; with hyperkalemia due to hemolysis.

Treatment hypoaldosteronism

Increased sodium chloride and fluid intake, mineralocorticoid drugs (0.5% DOXA injections of 1 ml 2-3 times a day, trimethyl acetate 1 ml once every 2 weeks, florinef 0.5-2 mg/day, cortinef 0.1 mg, DOXA tablets 0.005 - 1-3 times a day). Glucocorticoids are ineffective even in very high doses, especially during periods of exacerbation.

Treatment of pseudohypoaldosteronism involves only the administration of sodium chloride, since the kidneys “escape” the mineralocorticoid influence of the corresponding drugs.