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Apparent mineralocorticoid excess syndromes (including chronic licorice ingestion)

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


The syndrome of apparent mineralocorticoid excess (AME), a genetic disorder, and chronic ingestion of licorice (the root of glycyrrhiza glabra) or licorice-like compounds (such as carbenoxolone) can result in findings similar to those in primary aldosteronism: hypertension, hypokalemia, metabolic alkalosis, and low plasma renin activity. However, plasma aldosterone levels are low in these disorders, rather than elevated, as in primary aldosteronism. (See "Diagnosis of primary aldosteronism" and "Pathophysiology and clinical features of primary aldosteronism".)

The pathogenesis of these disorders has been elucidated. Summarized briefly, renal mineralocorticoid receptors bind aldosterone and cortisol with similar affinity. Although the plasma concentration of cortisol is approximately 100-fold higher than aldosterone, activation of mineralocorticoid receptors by cortisol is normally limited due to its conversion to inactive cortisone at the sites of aldosterone action by the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2) [1]. This conversion is impaired in AME because of a mutation in the 11-beta-HSD2 gene and with licorice ingestion because of a compound in licorice (glycyrrhetinic acid) that inhibits the enzyme [2]. (See 'Pathogenesis' below.)

By somewhat different mechanisms, hypersecretion of cortisol can also induce an excess mineralocorticoid state in patients with ectopic ACTH syndrome [3]. (See 'Ectopic ACTH syndrome' below.)

Other hypermineralocorticoid states and a review of cortisol metabolism are provided separately. (See "Diagnosis of primary aldosteronism" and "Metabolism of adrenal steroids".)


Clinical manifestations — The syndrome of apparent mineralocorticoid excess (AME) is a rare form of severe juvenile hypertension that is usually transmitted as an autosomal recessive trait [4,5]. AME is characterized by low birth weight, failure to thrive, onset of severe hypertension in early childhood with extensive target organ damage, hypercalciuria and nephrocalcinosis from an unknown mechanism, and renal failure [6]. These manifestations are accompanied by all of the findings of primary aldosteronism (hypertension, hypokalemia, metabolic alkalosis, and low plasma renin activity) except for the low plasma aldosterone concentration. Affected patients may also have polyuria due to nephrogenic diabetes insipidus that is presumably induced by the chronic hypokalemia [4,7]. (See "Pathophysiology and clinical features of primary aldosteronism" and "Clinical manifestations and causes of nephrogenic diabetes insipidus", section on 'Hypokalemia'.)

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Literature review current through: Nov 2017. | This topic last updated: Dec 12, 2017.
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