Biochemical evidence of aldosterone overproduction and abnormal regulation in normotensive individuals with familial hyperaldosteronism type I.

We examined in detail biochemical characteristics of 10 normotensive individuals (6 females; age range, 11-43 yr) with glucocorticoid-suppressible hyperaldosteronism (familial hyperaldosteronism type I) in an attempt to understand the development of hypertension in this disorder. All were normokalemic (median plasma potassium, 3.7 +/- 0.4 mmol/L SD), and upright plasma aldosterone 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 x min) were suppressed (<13 pmol/L x min), and the aldosterone to PRA ratio (169.0 +/- 308.3) was elevated (>65) in all but one subject. All subjects had 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 seven subjects, or during a 1-h infusion of angiotensin II (2 ng/kg x min) in each of six subjects so studied. Serial, second-hourly (day-curve) aldosterone levels correlated tightly with cortisol (r = 0.79-0.97, P < 0.01 to 0.001), 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 studied, consistent with ACTH-regulated aldosterone production. In conclusion, biochemical evidence of excessive, abnormally regulated aldosterone production is present not only in hypertensive individuals with familial hyperaldosteronism type I, but also in those who are normotensive. The absence of hypertension in such individuals, therefore, cannot be attributed to lack of biochemical expression of the hybrid gene.