Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20, 22-desmolase) in a patient treated for 18 years.

Two siblings, a 9-week-old female and an 18-year-old male pseudohermaphrodite are described with deficient cholesterol side-chain cleavage activity. The female died untreated in 1954; the second sibling, a phenotypically female infant with 46 XY karyotype, was diagnosed at age 5 weeks. Massive adrenal hyperplasia was revealed by intravenous pyelography showing downward displacement of the kidneys. Secretion rates of cortisol, aldosterone, deoxycorticosterone and corticosterone were unmeasurable. Urinary 17-hydroxycorticosteroids (17-OHCS), tetrahydrocortisol, 17-ketosteroids (17-KS), pregnanetriol, pregnanediol, and delta 5-3 beta-ol steroids were not detected during prolonged administration of ACTH. Plasma concentrations and urinary excretion of gonadotrophins were increased. Gonadal mitochondria did not convert radiolabelled cholesterol to pregnenolone. The gluccocorticoid and mineralocorticoid deficiencies have been controlled well by steroid replacement therapy. Plasma ACTH concentrations and plasma renin activity remained strikingly elevated even when supraphysiologic doses of glucocorticoids and mineralocorticoids were given. Oestrogen replacement alone induced a pubertal growth spurt. The differential diagnosis, the effects of long-term steroid replacement therapy, and comparison with previously reported findings are discussed.