When hypokalemia occurs in conjunction with hypertension, plasma renin and aldosterone measurements help to determine underlying causes. Primary aldosteronism (PAL), a condition in which autonomous aldosterone overproduction leads to salt retention (causing hypertension and renin suppression) and potassium excretion, accounts for 5%–10% of hypertension, and if prolonged and severe enough, can lead to hypokalemia. Measurement of the aldosterone/renin ratio (increased in PAL) among hypertensive populations has shown that PAL is common, with most (>70%) of PAL patients being normokalemic. In these cases PAL masquerades as “essential” hypertension (1).
Renin and aldosterone are characteristically increased (but are sometimes normal), and the aldosterone/renin ratio is normal or low, in cases of secondary hyperaldosteronism that may occur in hypertensive patients who have been treated with thiazide diuretics and patients with renovascular hypertension or the rare reninoma. Conditions mimicking mineralocorticoid excess (with low-renin hypertension due to sodium retention, and hypokalemia) but with low aldosterone concentrations (unlike in PAL) include licorice overuse, which results in inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2); congenital 11β-HSD2 deficiency; Liddle syndrome (constitutive activation of the epithelial sodium channel); and conditions associated with adrenocorticotropic hormone excess (causing high deoxycorticosterone concentrations), including ectopic adrenocorticotropic hormone syndrome, congenital adrenal hyperplasia due to 11β-hydroxylase or 17α-hydroxylase deficiency, and glucocorticoid resistance syndrome (2). Hypokalemia due to gastroenterological potassium losses, such as in Bartter or Gitelmann syndromes, is generally accompanied by low blood pressure due to loss of sodium/plasma volume, resulting in typically increased (but sometimes normal) plasma renin and aldosterone.
Unless properly controlled, variables such as medications, posture, dietary sodium, time of day, and hypokalemia itself can affect and confound interpretation of plasma aldosterone and renin, and their ratio (3). When possible, avoidance of confounding variables involves withdrawing diuretics for at least 4 weeks and withdrawing other interfering drugs (e.g., β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium antagonists, and nonsteroidal antiinflammatory agents) for at least 2 weeks and substituting these agents with others with lesser effects (including verapamil slow release, hydralazine, and prazosin); encouraging a liberalized sodium diet; correcting hypokalemia with potassium supplements; and collecting blood midmorning with patients seated. Proper blood collection (without stasis) minimizes the risk of factitious increases in plasma potassium that may mask hypokalemia (3).
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- © 2009 The American Association for Clinical Chemistry