Mineralocorticoid‑Related and Genetic Causes of Metabolic Alkalosis

Hormonal Excess Syndromes

Cushing’s syndrome can produce metabolic alkalosis because excess cortisol has mineralocorticoid activity; aldosterone is usually suppressed unless cortisol and aldosterone are co‑secreted. 1
Primary aldosteronism (autonomous aldosterone secretion from adrenal adenoma or hyperplasia) leads to chloride‑responsive metabolic alkalosis by enhancing distal sodium reabsorption coupled with hydrogen secretion. 2

Apparent mineralocorticoid excess (11β‑hydroxysteroid dehydrogenase type 2 deficiency) permits cortisol to activate mineralocorticoid receptors, causing hypertension, hypokalemia, and metabolic alkalosis. 1
Licorice ingestion produces an acquired form of apparent mineralocorticoid excess by inhibiting 11β‑hydroxysteroid dehydrogenase type 2, leading to similar electrolyte disturbances. 1

Liddle syndrome results from activating mutations in epithelial sodium channel subunits; patients develop early‑onset hypertension with low renin and low aldosterone, accompanied by hypokalemia and metabolic alkalosis. 2
Bartter syndrome is a congenital salt‑losing tubulopathy that presents with hypokalemia, metabolic alkalosis, hypercalciuria, and hyperreninemic hyperaldosteronism, typically with normal or low blood pressure. 2
Gitelman syndrome is a milder, adult‑onset tubulopathy characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria, usually with normal blood pressure. 2

Pseudohypoaldosteronism type II (Gordon syndrome) is a familial hyperkalemic hypertension disorder; although aldosterone levels may vary, it commonly presents with hyperkalemia rather than the hypokalemia seen in most other alkalosis‑causing conditions. 2

Blood pressure assessment helps differentiate etiologies: salt‑wasting tubulopathies (e.g., Bartter, Gitelman) typically have normal or low blood pressure, whereas mineralocorticoid‑excess states (e.g., primary aldosteronism, Liddle syndrome) present with hypertension. 1