The pathogenesis of adrenal and extra adrenal hyperandrogenism

The data reviewed in this paper suggest that a factor other than ACTH which is suppressible by treatment with glucocorticoid, plays an essential role in the regulation of adrenal androgen production. Adrenal androgen biosynthesis probably takes place exclusively in specific androgen-secreting cells. That availability of androgen substrate alone e.g. 17OH-progesterone, is not sufficient to lead to hyperandrogenaemia is clear from data which was obtained from treated patients with the 21 hydroxylase deficiency type of congenital adrenal hyperplasia. In pituitary ACTH excess, cortisol production is relatively greater than that of androgens. In contrast, in some patients with ectopic ACTH production, the excess production of androgens is relatively greater than that of cortisol. Taken together, these observations suggest that a factor closely related to ACTH, i.e. a POMC fragment other than ACTH, plays an important role in the regulation of adrenal androgen production, that in Cushing's disease the ratio of ACTH to the androgen-stimulating fragment increases, and that in some patients with ectopic ACTH syndrome the ratio of ACTH to the alternative fragment may be decreased. In addition, the data reviewed are consistent with a model for the pathogenesis of idiopathic hirsutism and polycystic ovary syndrome whereby mild adrenal androgen excess is primary to the development of these disorders. However, the identity of the putative adrenal androgen stimulating hormone has yet to be established.