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Etiology, diagnosis, and treatment of hypoaldosteronism (type 4 RTA)

William F Young, Jr, MD, MSc
Section Editors
Richard H Sterns, MD
André Lacroix, MD
Deputy Editor
John P Forman, MD, MSc


Hypoaldosteronism should be considered in any patient with persistent hyperkalemia in whom there is no obvious cause such as renal failure or the use of potassium supplements or a potassium-sparing diuretic [1-3]. The rise in the plasma potassium in this disorder reflects the major role played by aldosterone in urinary potassium excretion. In addition to hyperkalemia, hypoaldosteronism is usually associated with a mild metabolic acidosis with a normal anion gap (ie, a hyperchloremic acidosis) which has been called type 4 renal tubular acidosis.

The pathophysiology, clinical manifestations, etiology, diagnosis, and treatment of hypoaldosteronism will be presented here. The evaluation of patients with hyperkalemia in general is discussed separately. (See "Causes and evaluation of hyperkalemia in adults".)


The major clinical manifestations in patients with hypoaldosteronism are hyperkalemia and a mild hyperchloremic metabolic acidosis. Hypoaldosteronism should be considered in any patient with persistent hyperkalemia in whom there is no obvious cause such as renal failure or the use of potassium supplements or a potassium-sparing diuretic [1-3].

Although aldosterone also promotes sodium retention, hypoaldosteronism is not typically associated with prominent sodium wasting (except in young children) because of the compensatory action of other sodium-retaining factors (such as angiotensin II and norepinephrine) [1]. Hyponatremia is also uncommon in patients with isolated aldosterone deficiency since there is no hypovolemia-induced stimulation of ADH release and because plasma cortisol, a tonic inhibitor of ADH release, is normal [1]. When hyponatremia is present, primary adrenal insufficiency should be suspected. In this disorder, the concurrent lack of cortisol is a potent stimulus to ADH secretion, leading to water retention and a fall in the plasma sodium concentration. (See "Hyponatremia and hyperkalemia in adrenal insufficiency".)

Hyperkalemia — Aldosterone acts by increasing the number of open sodium channels in the luminal membrane of the principal cells in the cortical collecting tubule, leading to increased sodium reabsorption. The ensuing removal of sodium from the tubular fluid makes the lumen electronegative, thereby creating an electrical gradient that favors the secretion of cellular potassium into the lumen through potassium channels in the luminal membrane (figure 1).


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Literature review current through: Sep 2016. | This topic last updated: Oct 28, 2015.
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