Clinical, biochemical and genetic approaches to the detection of familial hyperaldosteronism type I

Since detection of familial hyperaldosteronism type I (glucocorticoid-suppressible hyperaldosteronism) allows specific treatment of hypertension with dexamethasone, we compared clinical, biochemical and genetic approaches to detection.

We studied 22 affected patients, 21 from a single, large family and an additional adopted male. Plasma aldosterone, plasma renin activity and urinary 18-oxo-cortisol were measured by radioimmunoassay. The hybrid gene was demonstrated using either Southern blotting or a long polymerase chain reaction technique.

Thirteen out of 22 (59%) patients with familial hyperaldosteronism type I, but only four out of 12 (33%) under 20 years of age, were hypertensive. Plasma potassium and aldosterone were each normal in 20 out of 22 (91%), and unhelpful in diagnosis. Plasma renin activity, the aldosterone: plasma renin activity ratio and 18-oxo-cortisol were more sensitive, being abnormal in 20 out of 22 (91%), 19 out of 22 (86%) and 20 out of 20 (100%) patients, respectively. Aldosterone was unresponsive (<50% rise) to 2 h of upright posture following overnight recumbency in 15 out of 15 (100%) patients studied, and to angiotensin II infusion (2 ng/kg per min for 1 h) in 14 out of 14 patients (100%). Whereas all the abovementioned abnormalities are also characteristic of angiotensin II-unresponsive aldosterone-producing adenoma, marked aldosterone suppression following 4 days of dexamethasone (0.5 mg every 6 h) was sensitive and specific for familial hyperaldosteronism type I (n = 11). The hybrid gene was detectable in peripheral blood leucocyte DNA in all 22 affected patients by Southern blotting, and by a faster, long polymerase chain reaction method developed in our laboratory, both methods requiring only a single blood collection.

Should studies in other families confirm its universal applicability, long polymerase chain reaction should prove to be the most practical means of detecting familial hyperaldosteronism type I in laboratories equipped with this technique.