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, glucocorticoid-suppressible hyperaldosteronism) in asymptomatic, affected individuals is essential if death from stroke is to be prevented. 2. In 21 patients with FH-I (presence of the causative hybrid 11 beta-hydroxylase/aldosterone synthase gene confirmed by Southern blot testing), various biochemical parameters were compared as possible screening tests. 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 from false negatives. 4. Levels of the urinary 'hybrid' steroid, 18-oxocortisol, were elevated (P < 0.01) in all 15 patients tested (138.2 +/- 17.4 micrograms/g creatinine, range 41.6 +/- 281.0 micrograms/g) with no overlap when compared with 11 normals (9.7 +/- 1.3 micrograms/g, range 2.8-17.4 micrograms/g). 5. We conclude that measurement of urinary 'hybrid' steroids is probably the most rapid and reliable biochemical screening test currently available for FH-I, with confirmation dependent on demonstration of the hybrid gene by genetic techniques.