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 an androgen-secreting adrenal tumor or by adrenal hyperplasia. Malignant adrenal tumors may secrete excess androgens, cortisol, or mineralocorticoids (or all three), resulting in Cushing syndrome (see Adrenal Disorders: Cushing Syndrome) with suppression of 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 (see Endocrine Disorders in Children: 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 (see Endocrine Disorders in Children: Congenital Adrenal Hyperplasia) may have fusion of the labioscrotal folds and clitoral hypertrophy resembling male external genitalia, thus presenting as female pseudohermaphrodites. 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 men, the excess adrenal androgens may suppress gonadal function and cause infertility. Ectopic adrenal tissue in the testes may enlarge and simulate tumors.

Diagnosis

• 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 (Stein-Leventhal) syndrome (see Menstrual Abnormalities: Polycystic Ovary Syndrome (PCOS)). Adrenal virilism is confirmed by showing elevated levels of adrenal androgens. In adrenal hyperplasia, urinary dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are elevated, pregnanetriol 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 30 min after administration of cosyntropinSome Trade Names
CORTROSYN
Click for Drug Monograph
(synthetic ACTH) 0.25 mg IM strongly suggests the most common form of adrenal hyperplasia.

Virilizing tumors are excluded if dexamethasoneSome Trade Names
DECADRON
DEXASONE
HEXADROL
Click for Drug Monograph
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.

Treatment

• Oral corticosteroids for hyperplasia
• Removal of tumors

Recommended treatment for adrenal hyperplasia is dexamethasoneSome Trade Names
DECADRON
DEXASONE
HEXADROL
Click for Drug Monograph
0.5 to 1 mg po 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 prednisoneSome Trade Names
DELTASONE
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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, hydrocortisoneSome Trade Names
CORTEF
SOLU-CORTEF
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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 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 dexamethasoneSome Trade Names
  DECADRON
  DEXASONE
  HEXADROL
  Click for Drug Monograph
  ; tumors require adrenalectomy.

Last full review/revision August 2012 by Ashley B. Grossman, MD, FRCP, FMedSci

Content last modified November 2012