Adrenal Virilism

Effects depend on the patient’s sex and age at onset and are more noticeable in women than in men.

Female infants with congenital adrenal hyperplasia Overview of Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia is a group of genetic disorders, each characterized by inadequate synthesis of cortisol, aldosterone, or both. In the most common forms, accumulated hormone precursors... read more may have fusion of the labioscrotal folds and clitoral hypertrophy resembling male external genitalia, thus presenting as a disorder of sexual differentiation.

In prepubertal children, growth may accelerate. If untreated, premature epiphyseal closure and short stature in adulthood occur. Affected prepubertal males may experience premature sexual maturation.

Adult females may have amenorrhea, atrophy of the uterus, clitoral hypertrophy, decreased breast size, acne, hirsutism, deepening of the voice, baldness, increased libido, and increased muscularity.

In adult males, the excess adrenal androgens may suppress gonadal function and cause infertility. Ectopic adrenal tissue in the testes may enlarge and simulate tumors.

Adrenal virilism is suspected clinically, although mild hirsutism and virilization with hypomenorrhea and elevated plasma testosterone may also occur in polycystic ovary syndrome Polycystic Ovary Syndrome (PCOS) Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more (Stein-Leventhal syndrome). Adrenal virilism is confirmed by showing elevated levels of adrenal androgens.

In adrenal hyperplasia, urinary dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are elevated, pregnanetriol (a metabolite of 17-hydroxyprogesterone) excretion is often increased, and urinary free cortisol is normal or diminished. Plasma DHEA, DHEAS, 17-hydroxyprogesterone, testosterone, and androstenedione may be elevated. A 17-hydroxyprogesterone level of > 30 nmol/L (1000 ng/dL) 30 minutes after administration of cosyntropin (synthetic ACTH) 0.25 mg IM strongly suggests the most common form of adrenal hyperplasia, which is 21-hydroxylase deficiency Congenital Adrenal Hyperplasia Caused by 21-Hydroxylase Deficiency 21-Hydroxylase (CYP21A2) deficiency causes defective conversion of adrenal precursors to cortisol and, in some cases, to aldosterone, sometimes resulting in severe hyponatremia and hyperkalemia... read more .

Virilizing tumors are excluded if dexamethasone 0.5 mg orally every 6 hours for 48 hours suppresses production of excess androgens. If excessive androgen excretion is not suppressed, CT or MRI of the adrenals and ultrasonography of the ovaries are done to search for a tumor.

Glucocorticoids are used for adrenal hyperplasia, typically oral hydrocortisone 10 mg on arising, 5 mg at midday, and 5 mg in the late afternoon. Alternatively, dexamethasone 0.5 to 1 mg orally may be given at bedtime, but even these small doses may cause signs of Cushing syndrome; therefore, this form of glucocorticoid is generally not recommended. Giving the dose at bedtime is most appropriate in terms of suppressing ACTH secretion but may cause insomnia. Cortisone acetate 25 mg orally once a day or prednisone 5 or occasionally up to 10 mg orally once a day can be used instead. Slower-release forms of hydrocortisone are also available and may provide better biochemical control.

Although most symptoms and signs of virilism disappear with treatment, hirsutism and baldness disappear slowly, the voice may remain deep, and fertility may be impaired.

Tumors require adrenalectomy. For patients with cortisol-secreting tumors, hydrocortisone should be given preoperatively and postoperatively because their nontumorous adrenal cortex will be atrophic and suppressed.