Hypoaldosteronism

Hypoaldosteronism is defined as a deficiency of aldosterone. Renal secretion of potassium is decreased, causing hyperkalaemia. The treatment is replacement of a mineralocorticoid, e.g. fludrocortisone. 

Hyperkaiemia Hyperkalemia may develop, probably due to induced hypoaldosteronism. Use with caution in patients with diabetes or renal insufficiency. Monitor patient closely. 

The naturally occurring mineralocorticosteroid is aldosterone. Its release is not ACTH dependent but is stimulated under control of the renin-angiotensin system. Aldosteron is not in clinical use because of its short halflife (20 min). Fludrocortisone is a synthetic analogue with considerably more potent mineralocorticoid than glucocorticoid activity. It is used as substitution therapy in adrenocorticoid insufficiency and in low-renin hypoaldosteronism. It is well absorbed orally and its effects last 1-2 days. 

Hauffa BP, Solyom J, Glaz E, Shackleton CH, Wambach G, Vecsei P, Stolecke H, Homoki J (1991) Severe hypoaldosteronism due to corticosterone methyl oxidase type II deficiency in two boys metabolic and gas chromatography-mass spectrometry studies. Eur J Pediatr 150 149-153... 

Hypoaldosteronism with metabolic acidosis has been reported in a child taking benazepril (176). 

The authors pointed out that there is evidence of ACE inhibitor-induced hypoaldosteronism in adults. This condition should be considered in children and adults taking ACE inhibitors who present with metabolic acidosis. 

Heparin-induced hypoaldosteronism is well documented, both in patients treated with standard heparin, even at low doses, and in patients treated with low molecular weight heparin (477,478). The most important mechanism of aldosterone inhibition appears to be a reduction in both the number and affinity of angiotensin II receptors in the zona glomerulosa (477). A direct effect of heparin on aldosterone synthesis, with inhibition of conversion of corticosterone to 18-hydroxycorticosterone, has also been suggested. This effect is believed to be responsible for the hyperkalemia that can occur in heparin-treated patients with impaired renal function and particularly in patients on chronic hemodialysis (479), or with diabetes mellitus, or who are taking other potentially hyperkalemic drugs. 

Levesque H, Cailleux N, Noblet C, Gancel A, Moore N, Courtois H. Hypoaldosteronisme induit par les heparines de bas poids moleculaire. [Hypoaldosteronism induced by low molecular weight heparins.] Presse Med 1991 20(1) 35. 

Treatment with angiotensin-converting enzyme inhibitors is also more likely to be associated with hyperkalemia in older individuals (69). Impaired angiotensin II formation limits this potent stimulus for aldosterone secretion, and this is superimposed on the already age-related decrease in activity of the renin-angiotensin-aldosterone axis. The same drug-induced hyporeninemic hypoaldosteronism is predicted for the angiotensin receptor blockers. However, to date this has not been documented clincally. 

ACE inhibitors can cause hyperkalemia because they inhibit the release of aldosterone. The effect is usually not significant in patients with normal renal function. However, in patients with impaired kidney function and/or in patients taking potassium supplements (including salt substitutes) or potassium-sparing diuretics, and especially aldosterone antagonists, hyperkalemia can occur. In two cases, hypoaldosteronism with diabetes was implicated (53,54). 

Uchida K, Azukizawa S, Nakano S, Kaneko M, Kigoshi T, Morimoto S, Matsui A. Reversible hyperkalemia during antihypertensive therapy in a hypertensive diabetic patient tvith latent hypoaldosteronism and mild renal failure. South Med J 1994 87(ll) 1153-5. 

Bonnet F, Thivolet CH. Reversible hyperkalemia at the initiation of ACE inhibitors in a young diabetic patient tvith latent hyporeninemic hypoaldosteronism. Diabetes Care 1996 19(7) 781. 

Heparin-induced hypoaldosteronism is well documented, both in patients treated with standard heparin, even at... 

Hyperkalemia is an occasional complication of heparin therapy. It has been attributed to hypoaldosteronism, and fludrocortisone has been used to treat it (12). It has been suggested that marked hyperkalemia is only likely to occur in the presence of other factors that alter potassium balance (13). 

Kalin ME, Poretsky E, Seres DS, Zumoff B. Hyporeninemic hypoaldosteronism associated with acquired immune deficiency syndrome. The American journal of medicine. 1987 May 82(5) 1035-8. 

Tan SY, Shapiro R, Franco R et al. Indomethacin-induced prostaglandin inhibition with hyperkalemia. A reversible cause of hy-poreninemic hypoaldosteronism. Annals of Internal Medicine 1979 90 783-785. 

ACE inhibitors and ARBs slow the progression of diabetic kidney disease. A trial that was reported in 2000 confirmed that even nonmicroalbuminuric type 2 diabetic patients should be managed with ACE inhibitors or ARBs to prevent cardiovascular events.In addition to lowering systemic blood pressure, such patients also have lowered glomerular capillary blood pressure and protein filtration,ACE inhibitors and ARBs also reduce All-medi-ated effects on glomerular permeability and cell proliferation and fibrosis and should be incorporated into the treatment schedules of all patients with type 2 diabetes and those with type 1 diabetes and microalbuminuria, ACE inhibitors may exacerbate hyperkalemia in patients with advanced CKD and/or hyporeninemic hypoaldosteronism. In older patients with renal artery stenosis, they may cause a rapid decline in kidney function. Pooled data from large clinical trials indicated above show that only 1.5% of patients treated with ACE inhibitors or ARBs were withdrawn from trials because of hyperkalemia, and no deaths were reported as a consequence of hyperkalemia. ... 

Selective Aldosterone Deficiency (Type IV RTA). In type IV RTA, there is failure of distal potassium and hydrogen ion secretion because of aldosterone deficiency or resistance. This may occur because of a range of steroid or steroid receptor synthetic defects or because of hyporeninemic hypoaldosteronism (e.g., due to diabetic nephropathy, tubulointerstitial disease, urinary obstruction, renal transplantation, or SLE). Hyperkalemia, although mild, is a usual manifestation. 

Interpretation Responses must be defined for the assay technique used. Patients with renin-dependent forms of hypertension (e.g., renovascular hypertension) show values that are approximately five times normal. Stimulated responses are also seen in patients with high-renin essential hypertension, pheochromocytoma, and Barttei s syndrome. Patients with hypertension firom mineralocorticoid excess (e.g., primary aldosteronism) usually have PRA below the concentration of assay sensitivity. Patients with hyporeninemic hypoaldosteronism usually have low concentrations of plasma renin and low aldosterone concentrations. Figure 51-17 shows typical responses. 

Other unusual conditions that suggest aldosterone excess or deficiency but are not connected to the renin-angiotensin-aldosterone system include Liddle s syndrome (pseudo hyper aldosteronism),which resembles primary aldosteronism clinically, but aldosterone production is low and hypertension is absent and Barttefs syndrome,which involves a prostaglandin-mediated renal potassium wasting and renal chloride handling defect, in which both aldosterone concentrations and renin activities are elevated. In renal tubular acidosis and pseudohypoaldosteronism, the clinical picture of hypoaldosteronism is seen concurrent with greater-than-normal concentrations of aldosterone. 

Melby JC, Azar ST. Hypoaldosteronism and mineralo-corticoid resistance. In Besser M, Burger HG, Jameson JL, eds. Endocrinology, 3rd ed. Philadelphia WB Saunders Co, 1995 1804-12. 

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