Adrenogenital syndrome

Adrenogenital syndrome (adrenal virilism) is a syndrome in which excess adrenal androgens cause virilization.

The diagnosis is clinical, confirmed by elevated androgen levels with and without dexamethasone suppression; adrenal imaging with biopsy if a mass lesion is identified may be required to determine the underlying cause. Treatment of adrenogenital syndrome depends on the cause.

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Causes adrenogenital syndrome

The cause of adrenogenital syndrome may be an androgen-secreting tumor of the adrenal gland or adrenal hyperplasia. Sometimes the tumor secretes excess androgens and cortisol, which leads to the development of Cushing's syndrome with suppression of ACTH secretion and atrophy of the contralateral adrenal gland.

Adrenal hyperplasia is usually congenital; late virilizing adrenal hyperplasia is a congenital variant. Both are caused by defects in the hydroxylation of cortisol precursors, causing them to accumulate and be used to produce androgens. In late virilizing hyperplasia, the defect is partial, so clinical manifestations may not occur until adulthood.

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Symptoms adrenogenital syndrome

The effects depend on the patient's gender and age at the onset of the disease, and are more noticeable in women. Symptoms and signs include hirsutism (in mild cases, this may be the only sign), baldness, acne, and voice changes (coarsening). Libido may increase. Prepubertal children may experience accelerated growth. Prepubertal boys may experience early puberty. Girls may develop amenorrhea, uterine atrophy, clitoral hypertrophy, breast reduction, and masculinization.

In adult males, excess adrenal androgens can suppress gonad function and cause infertility. Ectopic adrenal tissue in the testicles can enlarge and simulate a tumor.

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Diagnostics adrenogenital syndrome

Adrenogenital syndrome is suspected on clinical grounds, although mild hirsutism and virilization with hypomenorrhea and elevated plasma testosterone levels may also be seen in polycystic ovary syndrome (Stein-Leventhal). The diagnosis of adrenal virilization is confirmed by elevated levels of adrenal androgens. In adrenal hyperplasia, urinary dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are elevated, pregnanetriol excretion is often increased, and free cortisol levels are decreased. Plasma levels of DHEA, DHEAS, 17-hydroxyprogesterone, testosterone, and androstenedione may be elevated. A 17-hydroxyprogesterone level greater than 30 nmol/L 30 minutes after intramuscular administration of 0.25 mg cosyntropin ACTH is characteristic of the most common form of adrenal hyperplasia.

Virilizing tumors are excluded if dexamethasone 0.5 mg orally every 6 hours for 48 hours suppresses excess androgen production. If suppression does not occur, CT and MRI of the adrenal glands and ultrasound of the ovaries are necessary to search for a tumor.

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Treatment adrenogenital syndrome

The recommended treatment for adrenal hyperplasia is oral dexamethasone 0.5-1 mg at bedtime, but even at these low doses, signs of Cushing's syndrome may develop. Alternatively, cortisone (25 mg once daily) or prednisolone (5-10 mg once daily) may be used. Although the adrenogenital syndrome and its symptoms resolve, hirsutism and alopecia are slow to resolve, the voice may remain rough, and fertility may be impaired.

In tumors, adrenalectomy is necessary. Patients with cortisol-secreting tumors require hydrocortisone before and after surgery, since non-tumorous areas of the cortex will atrophy and be suppressed.