Late onset 21-hydroxylase deficiency is a genetic variant of the classic form of congenital adrenal hyperplasia (CAH)

Three young adult women with the diagnosis of idiopathic hirsutism had markedly abnormal elevations of serum 17-hydroxyprogesterone (17HP) in response to an ACTH stimulation test, indicating a mild degree of 21-hydroxylase deficiency. All three had oligoamenorrhea, exhibited no virilization and had reached a normal adult height. One had pubarche at 6 yrs. An ACTH stimulation test and HLA typing was performed on all available family members. Five of the 6 parents had elevations of 17HP comparable to those found in carriers of classic CAH. Two of the 3 propositi had HLA identical adult male siblings of normal height and masculinization with an identical abnormality in 17HP response to ACTH. One of the affected males developed intratesticular adrenal rest tumors that were reduced in size after dexamethasone therapy. Three HLA nonidentical sisters to the propositi were not affected. One patient married a CAH heterozygote and had two biochemically affected children (female 7 yrs and male 3 yrs) with normal heights, bone ages, and no signs of virilization, except for mildly increased terminal hair on the face and extremities of the daughter. We conclude that late onset congenital adrenal hyperplasia is a genetic variant of CAH with a milder enzymatic block and attenuated clinical expression. The affected gene is linked to the HLA locus. The presentation in females is that of mild masculinization. Males are asymptomatic but adrenal rest tumors in the testes may occur.