(See also Overview of Adrenal Function Overview of Adrenal Function The adrenal glands, located on the cephalad portion of each kidney (see figure Adrenal glands), consist of a Cortex Medulla The adrenal cortex and adrenal medulla each have separate endocrine... read more .)
Adrenal virilism is caused by
Androgen-secreting adrenal tumors
Malignant adrenal tumors may secrete excess androgens, estrogens, cortisol, mineralocorticoids (or combinations of the four). If there is cortisol hypersecretion, Cushing syndrome Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more results, with suppression of adrenocorticotropic hormone (ACTH) secretion and atrophy of the contralateral adrenal as well as hypertension. Adrenal tumors that secrete androgens cause virilization.
Adrenal hyperplasia is usually congenital; delayed virilizing adrenal hyperplasia is a variant of 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 . Both are caused by a defect in hydroxylation of cortisol precursors, most commonly 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 , or the much milder condition of 11beta-hydroxylase deficiency Congenital Adrenal Hyperplasia Caused by 11Beta-Hydroxylase Deficiency 11Beta-hydroxylase (CYP11B1) deficiency involves defective production of cortisol, with accumulation of mineralocorticoid precursors, resulting in hypernatremia, hypokalemia, and hypertension... read more .; 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 of 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.
Diagnosis of Adrenal Virilism
Other adrenal androgens (dehydroepiandrosterone [DHEA] and its sulfate [DHEAS], androstenedione)
Dexamethasone suppression test
Sometimes adrenocorticotropic hormone (ACTH) stimulation test
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.
Treatment of Adrenal Virilism
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 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.
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.
Do dexamethasone suppression testing and adrenal imaging to look for androgen-producing adrenal tumors.
Measure adrenal hormone intermediate metabolites and do adrenocorticotropic hormone (ACTH) stimulation testing to look for congenital adrenal hyperplasia.
Hyperplasia is treated with corticosteroid therapy; tumors require adrenalectomy.
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