Late‐Onset Congenital Adrenal Hyperplasia

The finding of biochemical abnormalities suggestive of congenital adrenal hyperplasia (CAH) in subjects who had no clinical manifestation of the disease in childhood has been variously referred to as the postpubertal, delayed-onset, partial, acquired, attenuated, mild, adult-onset, cryptic, nonclassical, and late-onset form of the disease.' At puberty the clinical features of this form of CAH are extremely variable, ranging from totally asymptomatic subjects to patients with moderate to severe hirsutism and menstrual disorder^.^.^ In our series of 18 postpubertal subjects with hirsutism and high basal 17-OH PG levels (>7.5 ng/ml), four presented with primary amenorrhea, seven with primary oligomenorrhea (occurring immediately postmenarche), one with secondary oligomenorrhea (occurring after 1-2 years of postmenarche cycles of normal length), one with secondary amenorrhea, four with ovulatory cycles, and one with anovulation. All of these subjects displayed hirsutism. We had also a case with normal ovulatory cycles without hirsutism; normal serum androgens. ACTH, and cortisol; and 17-OH PG levels of >20 ng/ml. This condition is distinguished from other etiologies on the basis of an estimate of serum 17-OH PG, which is a marker of the enzymatic defect responsible for the deviation of steroidogenesis in favor of androgen production. Certain authors believe that an increase of basal serum 17-OH PG levels is the hallmark of the diagnosis, whereas others are of the opinion that the most sensitive diagnostic test is the ACTH-induced rise in 17-OH PG.4-6 From the point of view of a purely differential diagnosis, the first opinion is more acceptable. In the presence of normal 17-OH PG levels, it would be unreasonable to attribute a hyperandrogenemic state to 2 1 -hydroxylase deficiency, because this steroid is the more sensitive marker of and the first to be affected in this condition. This assumption also stands true for subjects with normal basal serum 17-OH PG in whom a high post-ACTH rise in 17-OH PG is observed, because it is the secretion and serum concentration of androgens in basal conditions that may induce pathophysiological changes and not their episodic increase in the rare case of severe stress, causing an increased release of endogenous ACTH. This reasoning leads to two assumptions: (a) first, in cases with basal 17-OH PG levels within the normal range, any clinical or biological evidence of androgen excess must arise from causes other than 21-hydroxylase deficiency and should be treated accordingly; (b) second, in cases with high basal 17-OH PG levels, one would expect a parallel between 17-OH PG concentrations and hyperandrogenemia. In a series of 359 consecutive cases with hirsutism, mostly young subjects, single