ADRENAL STEROIDOGENESIS IN HETEROZYGOTES FOR 21-HYDROXYLASE DEFICIENCY

Adrenal steroidogenesis has been studied in vivo in eight obligate heterozygotes (six men and two women) for 21‐hydroxylase deficiency and the results compared with twenty‐one normal subjects. Serum levels of nine steroids on the biosynthetic pathway (the Δ53β‐hydroxysteroids, pregnenolone (Pe), 17α‐hyd‐roxypregnenolone (17Pe), dehydroepiandrosterone (DHEA), androstenediol (Adiol), and their Δ4 3‐keto counterparts, progesterone (Po), 17α‐hydroxypro‐gesterone (17Po), androstenedione (Adione), testosterone (T)) as well as corti‐sol were measured following ACTH stimulation from a dexamethasone‐sup‐pressed state. There was evidence of reduced 21‐hydroxylase activity in the heterozygotes when the results were compared with the usual pattern of response seen in nineteen of twenty‐two normal subjects. Thus the increment at 1 h for 17α‐hydroxyprogesterone was greater in all the heterozygotes and three of them (one man, two women) also had a greater increment for progesterone. 17,20 desmolase activity may also be reduced in the heterozygotes for they had a lower increment than normal of dehydroepiandrosterone and androstenediol. The results were complicated by the finding that three additional subjects in the normal population tested have much greater 17Po and Po responses than the majority and clearly form a separate population. Our data suggest that there is a common variant within the normal population which may result from the heterozygous state of 21‐hydroxylase deficiency; alternatively other forms of 21‐hydroxylase may exist with reduced activity that even in the homozygous state may not produce clinical disease. Copyright © 1979, Wiley Blackwell. All rights reserved