EVIDENCE FOR PERSISTENT DYSFUNCTION OF WILD-TYPE ALDOSTERONE SYNTHASEGENE IN GLUCOCORTICOID-TREATED FAMILIAL HYPERALDOSTERONISM TYPE-I

Background In familial hyperaldosteronism type I (FH-I), glucocorticoi d treatment suppresses adrenocorticotrophic hormone-regulated hybrid g ene expression and corrects hyperaldosteronism. Objective To determine whether the wild-type aldosterone synthase genes, thereby released fr om chronic suppression, are capable of functioning normally. Methods W e compared mid-morning levels of plasma potassium, plasma aldosterone, plasma renin activity (PRA) and aldosterone : PRA ratios, measured wi th patients in an upright position, and responsiveness of aldosterone levels to infusion of angiotensin II (AII), for 11 patients with FH-I before and during long-term (0.8-14.3 years) treatment with 0.25-0.75 mg/day dexamethasone or 2.5-10 mg/day prednisolone. Results During glu cocorticoid treatment, hypertension was corrected in all. Potassium le vels, which had been low (< 3.5 mmol/l) in two patients before treatme nt, were normal in all during treatment (mean 4.0 +/- 0.1 mmol/l, rang e 3.5-4.6). Aldosterone levels during treatment [13.2 +/- 2.1 ng/100 m l (mean +/- SEM)] were lower than those before treatment (20.1 +/- 2.5 ng/100 ml, P < 0.05). PRA levels, which had been suppressed before tr eatment (0.5 +/- 0.2 ng/ml per h), were unsuppressed during treatment (5.1 +/- 1.5 ng/ml per h, P < 0.01) and elevated (> 4 ng/ml per h) in six patients. Aldosterone : PRA ratios, which had been elevated (> 30) before treatment (101.1 +/- 25.9), were much lower during treatment ( 4.1 +/- 1.0, P < 0.005) and below normal (< 5) in eight patients. Surp risingly, aldosterone level, which had not been responsive (< 50% rise ) to infusion of AII for all 11 patients before treatment, remained un responsive for 10 during treatment. Conclusions Apparently regardless of duration of glucocorticoid treatment in FH-I, aldosterone level rem ains poorly responsive to AII, with a higher than normal PRA and a low aldosterone : PRA ratio. This is consistent with there being a persis tent defect in functioning of wild-type aldosterone synthase gene. (C) Rapid Science Publishers ISSN 0263-6352.