HYBRID GENE OR HYBRID STEROIDS IN THE DETECTION AND SCREENING FOR FAMILIAL HYPERALDOSTERONISM TYPE-I

1. Early diagnosis of Familial Hyperaldosteronism Type I (FH-I, glucoc orticoid-suppressible hyperaldosteronism) in asymptomatic, affected in dividuals is essential if death from stroke is to be prevented. 2. In 21 patients with FH-I (presence of the causative hybrid 11 beta-hydrox ylase/aldosterone synthase gene confirmed by Southern blot testing), v arious biochemical parameters were compared as possible screening test s. Hypokalaemia and elevated plasma aldosterone each detected only two (10%) of the affected individuals. 3. Plasma renin activity 19 (90%) and aldosterone/renin ratio 18 (86%) were more reliable but not free f rom false negatives. 4. Levels of the urinary 'hybrid' steroid, 18-oxo cortisol, were elevated (P<0.01) in ail 15 patients tested (138.2+/-17 .4 mu g/g creatinine, range 41.6-281.0 mu g/g) with no overlap when co mpared with 11 normals (9.7+/-1.3 mu g/g, range 2.8-17.4 mu g/g). 5. W e conclude that measurement of urinary 'hybrid' steroids is probably t he most rapid and reliable biochemical screening test currently availa ble for FH-I, with confirmation dependent on demonstration of the hybr id gene by genetic techniques.