Biochemical evidence of aldosterone overproduction and abnormal regulationin normotensive individuals with familial hyperaldosteronism type I

We examined in detail biochemical characteristics of 10 normotensive indivi duals (6 females; age range, 11-43 yr) with glucocorticoid-suppressible hyp eraldosteronism (familial hyperaldosteronism type I) in an attempt to under stand the development of hypertension in this disorder. All were normokalem ic (median plasma potassium, 3.7 +/- 0.4 mmol/L SD), and upright plasma ald osterone levels (478 +/- 333 pmol/L) were within the normal range (140-1110 pmol/L) in nine subjects. However, upright PRA. levels (3.3 +/- 30.5 pmol/ L.min) were suppressed (<13 pmol/L.min), and the aldosterone to PRA ratio ( 169.0 +/- 308.3) was elevated (>65) in all but one subject. All subjects ha d elevated 24-h urinary levels of 18-oxo-cortisol (34.3 +/- 11.2 nmol/mmol creatinine; normal range, 0.8-6.5 nmol/mmol creatinine). Plasma aldosterone failed to rise by at least 50% during 2 h of upright posture in five of se ven subjects, or during a l-h infusion of angiotensin II (2 ng/kg.min) in e ach of six subjects so studied. Serial, second-hourly (day-curve) aldostero ne levels correlated tightly with cortisol (r = 0.79-0.97, P < 0.01 to 0.00 1), but not with PRA (r = 0.13-0.40, not significant) levels in each of six subjects, and plasma aldosterone suppressed to less than 110 pmol/L during 4 days of dexamethasone administration (0.5 mg 6 hourly) in each of two st udied, consistent with ACTH-regulated aldosterone production. In conclusion , biochemical evidence of excessive, abnormally regulated aldosterone produ ction is present not only in hypertensive individuals with familial hyperal dosteronism type I, but also in those who are normotensive. The absence of hypertension in such individuals, therefore, cannot be attributed to lack o f biochemical expression of the hybrid gene.