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Adrenal Virilism

(Adrenogenital Syndrome)

By Ashley B. Grossman, MD, Emeritus Professor of Endocrinology; Professor of Neuroendocrinology; Consultant NET Endocrinologist, University of Oxford; Fellow, Green-Templeton College; Barts and the London School of Medicine; Royal Free Hospital, London

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Patient Education

Adrenal virilism is a syndrome in which excessive adrenal androgens cause virilization. Diagnosis is clinical and confirmed by elevated androgen levels with and without dexamethasone suppression; determining the cause may involve adrenal imaging. Treatment depends on the cause.

Adrenal virilism is caused by

  • Androgen-secreting adrenal tumors

  • Adrenal hyperplasia

Malignant adrenal tumors may secrete excess androgens, cortisol, or mineralocorticoids (or all three), resulting in Cushing syndrome with suppression of adrenocorticotropic hormone (ACTH) secretion and atrophy of the contralateral adrenal as well as hypertension.

Adrenal hyperplasia is usually congenital; delayed virilizing adrenal hyperplasia is a variant of congenital adrenal hyperplasia. Both are caused by a defect in hydroxylation of cortisol precursors; cortisol precursors accumulate and are shunted into the production of androgens. The defect is only partial in delayed virilizing adrenal hyperplasia, so clinical disease may not develop until adulthood.

Symptoms and Signs

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 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 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.


  • Testosterone

  • Other adrenal androgens (dehydroepiandrosterone sulfate [DHEAS], androstenedione)

  • Dexamethasone suppression test

  • Adrenal imaging

  • 17-hydroxyprogesterone

Adrenal virilism is suspected clinically, although mild hirsutism and virilization with hypomenorrhea and elevated plasma testosterone may also occur in polycystic ovary syndrome (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 min after administration of cosyntropin (synthetic ACTH) 0.25 mg IM strongly suggests the most common form of adrenal hyperplasia.

Virilizing tumors are excluded if dexamethasone 0.5 mg po q 6 h for 48 h 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.


  • Oral glucocorticoids for hyperplasia

  • Removal of tumors

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 po may be given at bedtime, but even these small doses may cause signs of Cushing syndrome. Giving the dose at bedtime is most appropriate in terms of suppressing ACTH secretion but may cause insomnia. Cortisol 25 mg po once/day or prednisone 5 to 10 mg po once/day can be used instead. Although most symptoms and signs of virilism disappear, 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.

Key Points

  • Adrenal virilism is due to an androgen-secreting adrenal tumor or to adrenal hyperplasia.

  • Virilization is more noticeable in women; men may be infertile due to suppressed gonadal function.

  • Urinary and plasma dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) and often plasma testosterone are elevated.

  • ACTH stimulation testing and/or dexamethasone suppression testing may be done.

  • Hyperplasia is treated with dexamethasone; tumors require adrenalectomy.

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