A long look at the adrenogenital syndrome

There seems to be impressive evidence that congenital virilizing adrenal hyperplasia exists as a phenotypic spectrum - at one end the alarming manifestation of the salt-losing form of female hermaphroditism - and at the other end the mildest form of the troublesome triad of hirsuitism, oligomenorrhea and infertility. This concept provides problems for the geneticist who is repelled by the concept that disease A is a variant of disease B. It is necessary to leave this fascinating question for another time, but clearly we are dealing with phenotypic diversity due to unidentified genetic heterogeneity revolving about a pivotal enzyme defect, perhaps from an allelic series; but there are, however, many possibilities. From the evidence presented today it can be concluded that the mildest clinical manifestations may also be an expression of homozygosity. The important point for the practical gynecologist is that an understanding of the defect and of the therapy of the severe form of female hermaphroditism gives insight into an understanding of the more common troublesome triad and vice versa. There now seems to be impressive evidence that at least some patients of categories III and IV of the 1954 classification have a relative 21-hydroxylase deficiency.