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Adrenal Virilism

(Adrenogenital Syndrome)

By

Ashley B. Grossman

, MD, University of Oxford; Fellow, Green-Templeton College

Last full review/revision Jul 2019| Content last modified Jul 2019
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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). If there is cortisol hypersecretion, Cushing syndrome results, 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.

Diagnosis

  • Testosterone

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

  • 17-hydroxyprogesterone

  • Dexamethasone suppression test

  • Sometimes ACTH stimulation test

  • Adrenal imaging

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 minutes 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 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.

Treatment

  • 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 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 to 10 mg orally once a 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.

  • Dexamethasone suppression testing and/or adrenocorticotropic hormone(ACTH) stimulation testing may be done.

  • Hyperplasia is treated with corticosteroid therapy; tumors require adrenalectomy.

Drugs Mentioned In This Article

Drug Name Select Trade
CORTEF, SOLU-CORTEF
OZURDEX
RAYOS
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