3-Beta–hydroxysteroid dehydrogenase (3BHSD) deficiency is a rare form of congenital adrenal hyperplasia that results in decreased production of all 3 groups of adrenal steroids: mineralocorticoids, glucocorticoids, and sex steroids. In severely affected individuals, decreased mineralocorticoid secretion results in varying degrees of salt wasting in both males and females, and deficient androgen production results in ambiguous genitalia in 46,XY males. This condition is due to defects in type II 3-beta–hydroxysteroid dehydrogenase, an enzyme that occurs almost exclusively in the gonads and adrenal glands. A variety of mutations in the HSD3B2 gene affect the activity of this enzyme, resulting in the extremely variable, phenotypic presentations of 3-beta–hydroxysteroid dehydrogenase deficiency.
With severe deficiency, the most common presentation is that of a newborn infant with adrenal insufficiency due to both glucocorticoid and mineralocorticoid deficiency and ambiguous genitalia in 46,XY patients. Infants with less severe (non–salt-wasting) forms may be relatively asymptomatic.
Older patients with mild defects in 3-beta–hydroxysteroid dehydrogenase activity (late-onset or nonclassic variant) may present with premature pubic hair development, hirsutism, irregular menstrual cycles or primary amenorrhea.
Patients with classic salt-losing 3-beta–hydroxysteroid dehydrogenase require initial replacement of glucocorticoids and mineralocorticoid, plus the addition of sex steroids at appropriate, pubertal age.
The need for replacement therapy varies in late-onset (nonclassic) 3-beta–hydroxysteroid dehydrogenase deficiency and depends on the severity of the defect. Hydrocortisone (or other glucocorticoid) replacement therapy may be needed to suppress excess androgen production.
Prognosis is usually good-to-excellent with adequate replacement (as needed) of glucocorticoids, mineralocorticoid, and sex steroid therapy, monitoring and follow-up.