Reversal of diuretic-induced secondary hyperaldosteronism and hypokalemia by trilostane, an inhibitor of adrenal steroidogenesis.
Correction of diuretic-induced hypokalemia is usually accomplished by potassium supplementation or antagonism of aldosterone's renal action. This study sought to determine if inhibition of aldosterone biosynthesis could reverse diuretic-induced hypokalemia and whether trilostane would be clinically useful in this regard. Essential hypertensives (n = 22) were treated with hydrochlorothiazide (HCTZ) 50 mg/d, and patients who became hypokalemic were randomly assigned to receive in addition to HCTZ either a placebo (n = 7), trilostane 240 mg/d (Trilo 240) (n = 7), or trilostane 60 mg/d (Trilo 60) (n = 3). Following 12 weeks of therapy the placebo patients remained hypokalemic with hyperaldosteronism, while the patients who received Trilo 240 had a correction of hypokalemia and hyperaldosteronism (P less than .05) along with a reduction in diastolic blood pressure (P less than .05). The Trilo 60 patients, however, remained hypokalemic with no significant reduction in aldosterone excretion or blood pressure compared with HCTZ. Body weight and urinary free cortisol levels along with routine biochemical tests were unchanged during this study. Three Trilo 240 patients developed diarrhea but did not discontinue the study. These results demonstrate that trilostane can correct diuretic-induced hypokalemia by lowering aldosterone secretion. Furthermore, this reduction in aldosterone may enhance the antihypertensive effects of diuretic therapy.
Griffing
G T
GT
Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, MA 02118-2393.
Melby
J C
JC
D000450:Aldosterone / Q000031:analogs & derivatives / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004232:Diuretics / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D006929:Hyperaldosteronism / Q000139:chemically induced* / Q000188:drug therapy / Q000652:urine; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D007008:Hypokalemia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011188:Potassium / Q000097:blood; D011446:Prospective Studies; D011897:Random Allocation
D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D013196:Dihydrotestosterone; C013282:tetrahydroaldosterone; D000450:Aldosterone; C009954:trilostane; D011188:Potassium; D006854:Hydrocortisone