CLINICAL, BIOCHEMICAL AND GENETIC APPROACHES TO THE DETECTION OF FAMILIAL HYPERALDOSTERONISM TYPE-I

Aim: Since detection of familial hyperaldosteronism type I (glucocorti coid-suppressible hyperaldosteronism) allows specific treatment of hyp ertension with dexamethasone, we compared clinical, biochemical and ge netic approaches to detection. Patients and methods: We studied 22 aff ected patients, 21 from a single, large family and an additional adopt ed male. Plasma aldosterone, plasma renin activity and urinary 18-oxo- cortisol were measured by radioimmunoassay. The hybrid gene was demons trated using either Southern blotting or a long polymerase chain react ion technique. Results: Thirteen out of 22 (59%) patients with familia l hyperaldosteronism type I, but only four out of 12 (33%) under 20 ye ars of age, were hypertensive. Plasma potassium and aldosterone were e ach normal in 20 out of 22 (91%), and unhelpful in diagnosis. Plasma r enin 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. Aldos terone was unresponsive (<50% rise) to 2 h of upright posture followin g 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 pat ients (100%). Whereas all the abovementioned abnormalities are also ch aracteristic of angiotensin II-unresponsive aldosterone-producing aden oma, marked aldosterone suppression following 4 days of dexamethasone (0.5 mg every 6 h) was sensitive and specific for familiar hyperaldost eronism 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 ou r laboratory, both methods requiring only a single blood collection. C onclusions: Should studies in other families confirm its universal app licability, long polymerase chain reaction should prove to be the most practical means of detecting familial hyperaldosteronism type I in la boratories equipped with this technique.