Adrenal Virilism

Symptoms and signs depend on the patient’s sex and age at onset and are more noticeable in females than in males.

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 in adulthood occur. Affected prepubertal males may experience premature sexual maturation.

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

Hirsutism

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JOHN RADCLIFFE HOSPITAL/SCIENCE PHOTO LIBRARY

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.

• Urine levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), pregnanetriol, and cortisol

• Plasma hormone levels, including: testosterone, DHEA, DHEAS, androstenedione, and 17-hydroxyprogesterone

• Dexamethasone suppression test

• Sometimes adrenocorticotropic hormone (ACTH) stimulation test

• Adrenal imaging

Adrenal virilism is suspected based on physical findings of virilization, although the differential diagnosis includes polycystic ovary syndrome (or its most clinically severe form, Stein-Leventhal syndrome), which may present with mild hirsutism and virilization with hypomenorrhea and elevated plasma testosterone. Patients should also be asked about use of supplements or topical products, since some of these may be androgenic.

Adrenal virilism is confirmed by showing elevated urine and serum levels of adrenal androgens.

In congenital 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.

Provocative testing may include a dexamethasone suppression test and/or ACTH stimulation test.Provocative testing may include a dexamethasone suppression test and/or ACTH stimulation test.

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 ultrasound of the ovaries are done to search for a tumor.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 ultrasound of the ovaries are done to search for a tumor.

A 17-hydroxyprogesterone level of > 30 nmol/L (> 1000 ng/dL) 30 minutes after administration of cosyntropin (synthetic ACTH) 250 mcg IM strongly suggests 1000 ng/dL) 30 minutes after administration of cosyntropin (synthetic ACTH) 250 mcg IM strongly suggests21-hydroxylase deficiency.

Males who are inadequately treated may develop "adrenal rest" tumors of the testis, which generally do not need surgery and should shrink with adequate replacement.

• Oral glucocorticoids for congenital adrenal hyperplasia

• Resection of adrenal tumors, if present

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 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 ofCushing syndrome; therefore, dexamethasone 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 mg or occasionally up to 10 mg orally once a day can be used instead. Slower-release forms of 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 mg or occasionally up to 10 mg orally once a day can be used instead. Slower-release forms ofhydrocortisone may provide better biochemical control. ACTH antagonists that aim to decrease adrenal androgen production are under study (1), but patients will still require hydrocortisone replacement.), but patients will still require hydrocortisone replacement.

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

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