Hypoaldosteronism

Hypoaldosteronism is one of the least studied questions of clinical endocrinology. Information about this disease is not available in the manuals and in the textbooks of endocrinology, in spite of the fact that isolated hypoaldosteronism as an independent clinical syndrome is described more than 30 years ago.

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

Pathogenesis

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

Primary isolated hypoaldosteronism is most likely caused by a deficiency of two enzyme systems controlling the synthesis of aldosterone in the last stages: 18-hydroxylase (blocking the conversion of corticosterone to 18-hydroxycorticosterone, type I) and / or 18-dehydrogenase (block of transition of 18-oxycorticosterone to aldosterone, type II ). This violation of biosynthesis is more often congenital, manifested in infants or in early childhood. Symptoms are characterized by varying degrees of loss of salt, sometimes a violation of growth, the absence of sexual dysfunction. Loss of salt and vascular hypotension increase aldosterone-renin production (hypereneninemic hypoaldosteronism). Stimulant factors (orthostasis, diuretics, etc.) slightly increase the production of aldosterone. With age, this form tends to spontaneous remission.

A similar clinical syndrome with generalized or partial enzyme deficiency can be acquired and observed in adolescence and in adults. There are observations in which the acquired insufficiency of 18-dehydrogenase with the clinic of isolated hypoaldosteronism is combined with polyendocrine autoimmune insufficiency, including Hashimoto's goitre, 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 effect of the latter directly on the glomerular zone as a result of increased sodium excretion may overlap its stimulating renin-angiotensin effect. Pharmacological adrenalectomy of a wide spectrum is caused by eleptene, chloride, methopyron.

In addition to primary isolated hypoaldosteronism, secondary, associated with inadequate production of renin by the kidneys or the release of inactive renin (giporeninemic hypoaldosteronism) is observed. With this form, ARP and aldosterone production are poorly 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, giporeninemic hypoaldosteronism often accompanies and complicates the course of diseases such as diabetes mellitus, chronic nephritis with renal tubular acidosis and moderate impairment of renal function, in particular, a decrease in creatinine clearance. Universal vascular lesions, including kidneys, as well as ketoacidosis in diabetic patients create a number of prerequisites for the development of hypoaldosteronism. The most important of them: production of inactive renin, a deficiency of insulin, indirectly affecting the synthesis of aldosterone; decrease in adrenergic activity and prostaglandins E1 and E2, stimulating ARP. Disturbance of vegetative regulation with low adrenergic activity underlies giporeninemicheskogo gipologdosteronizma in Parkinson's disease and in the syndrome of orthostatic hypotension.

Hypoaldosteronism induced by a prolonged previous decrease in ARP may develop after removal of the aldosterome of one of the adrenals as a result of atrophy of the glomerular zone of the other. Having arisen soon after the operation, the characteristic periodic attacks of hypoaldosteronism gradually weaken and disappear as the ARP increases and the glomerular zone recovers.

Hypoaldosteronism in combination with insufficiency of cortisol production is observed in Addison's disease, after bilateral adrenalectomy, with a congenital disruption of the biosynthesis of corticosteroids in patients with adrenogenital syndrome.

Insufficiency of aldosterone promotes an increase in reabsorption, a decrease in secretion and excretion of potassium in the renal tubules. His delay, usually prevailing over the loss of sodium, leads to universal hyperkalemia. Hyperkaliemic hyperchloremic renal tubular acidosis reduces production and excretion of ammonium and enhances the tendency to azotemia, especially with primary renal involvement in diabetic patients. The severity of metabolic disorders determines the clinical symptomatology of primary hyperaldosteronism and its severity.

[4], [5], [6], [7]

Symptoms of the hypoaldosteronism

Isolated gipereninemic hypoaldosteronism as an independent clinical syndrome was first described by RV Hudson et al. This is a rare disease, observed mainly in men. It is characterized by general and muscular weakness, hypotension, dizziness, a tendency to fainting, a  bradycardia, at times reaching the degree of atrioventricular blockade, disturbances in the rhythm of breathing, down to Adams-Stokes fits with confusion and convulsions. The course of the disease is chronic and undulating. The periods of exacerbation with circulatory collapse alternate with spontaneous remissions. It is assumed that the possibility of unexpected improvements and a long "erased" course differing only in the tendency to orthostatic hypotension is determined by the compensatory increase in the production of glucocorticoids and catecholamines partially and temporarily replenishing the aldosterone deficiency.

In those cases when electrocution (hyperkaliemia, convulsions, paresthesia, reduction of renal filtration) is more pronounced in chronic adrenal insufficiency ( Addison's disease, state after bilateral adrenalectomy), one should think about the prevalence of mineralocorticoid insufficiency over the glucocorticoid.

[8], [9], [10], [11]

Forms

Insufficiency of aldosterone in the body can be:

• isolated;
• Combine with 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 violated (pseudohyperdosteronism).

[12], [13], [14], [15]

Diagnostics of the hypoaldosteronism

Laboratory diagnosis is based on a low level of aldosterone, hyperkalemia (6-8 meq / L), sometimes hyponatremia, increased sodium / potassium in urine and saliva, normal or elevated cortisol levels, 17-oxycorticosteroids and catecholamines in blood and urine. ARP depends on the form of the disease, with pseudohyperdosteronism there is a high level of both aldosterone and ARP. On the ECG, signs of hyperkalemia are recorded: lengthening of the PQ interval, bradycardia, this or that degree of transverse blockage, high acute pincer in the thoracic leads. It should be emphasized that hyperkalemic syndrome with a complex of cardiovascular disorders and orthostatic hypotonia of an unclear genesis require close attention of both therapists and endocrinologists.

[16]

Differential diagnosis

Differential diagnosis 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 11-hydroxylase defect; with the syndrome of orthostatic hypotension based on the defeat of the autonomic nervous system; with hypoaldosteronism in withdrawal syndrome after prolonged intake of mineralocorticoids; with hyperkalemia due to hemolysis.

Treatment of the hypoaldosteronism

Increased injection of sodium chloride and liquid, preparations of mineralocorticoid series (0.5% DOXA injections per 1 ml 2-3 times a day, trimethyl acetate 1 ml every 2 weeks, florinephs 0.5-2 mg / day, cortineph 0.1 mg, taking Doxas in tablets 0.005 - 1 -3 times a day). Glucocorticoids even in very high dosages are ineffective, especially during periods of exacerbation.

Treatment of pseudohyperdosteronism includes only the administration of sodium chloride, since the kidneys "escape" from the mineralocorticoid effect of the corresponding drugs.