Deficiency of 3β-hydroxysteroid dehydrogenase occurs with varying frequency in hirsute patients (191,192). The enzyme is found in both the adrenal glands and ovaries (unlike 21and 11-hydroxylase) and is responsible for transforming -5 steroids into the corresponding -4 compounds, a step integral to the synthesis of glucocorticoids, mineralocorticoids, and testosterone and estradiol. In severe forms, cortisol and mineralocorticoids are deficient. The clinical spectrum of 3β-hydroxysteroid dehydrogenase deficiency ranges from the classic salt wasting, hypogonadism, and ambiguous genitalia in males and females, to nonclassic hyperandrogenic symptoms in children and young women (193). In mild forms, elevated ACTH levels overcome these critical deficiencies, and the diagnosis of this disorder relies on the relationship of -5 and -4 steroids. A marked elevation of DHEA and DHEAS in the presence of normal, or mildly elevated, testosterone or androstenedione can suggest the initiation of a screening protocol for 3β-hydroxysteroid dehydrogenase deficiency using exogenous ACTH stimulation (191). Following intravenous administration of a 0.25-mg ACTH(1-24) bolus, within 60 minutes 17hydroxypregnenolone levels rise significantly in women with 3β-hydroxysteroid dehydrogenase deficiency, compared with normal women (2,276 ng/dL compared with normal of 1,050 ng/dL). The mean poststimulation ratio between 17-hydroxypregnenolone and 17-OHP is markedly elevated (mean ratio of 11 compared with 3.4 in normal controls and 0.4 in 21-hydroxylase deficiency). The rarity of this disorder indicates that routine screening of hyperandrogenic patients is not justified (191,192).
Treatment of Adult-Onset Congenital Adrenal Hyperplasia
Many patients with congenital AOAH do not need treatment. Glucocorticoid treatment should be avoided in asymptomatic patients with AOAH because the potential adverse effects of glucocorticoids probably outweigh any benefits (180,182).
Glucocorticoid therapy is recommended only to reduce hyperandrogenism for those with significant symptoms. Dexamethasone and antiandrogen drugs (both cross the placenta) should be used with caution and in conjunction with oral contraceptives in adolescent girls and young women with signs of virilization or irregular menses. When fertility is desired, ovulation induction might be necessary, and a glucocorticoid that does not cross the placenta (e.g., prednisolone or prednisone) should be used (179).
Many patients who are undiagnosed but who actually have AOAH are treated with therapies for ovarian hyperandrogenism and/or PCOS, with progestins for endometrial regulation, clomiphene or gonadotropins for ovulation induction, or progestins and antiandrogens for control of hirsutism. These therapies may be appropriate, as an alternative to glucocorticoid therapy, even when AOAH is recognized as the cause for the patient’s symptoms.