Hirsutism & Virilization

Key Features

Essentials of Diagnosis

• Hirsutism: increased hair, acne, menstrual disorders

• Virilization: increased muscularity, androgenic alopecia, deepening of the voice, clitoromegaly; rarely, a palpable pelvic tumor

• Urinary 17-ketosteroids, serum dehydroepiandrosterone sulfate (DHEAS) and androstenedione elevated in adrenal disorders, variable in others

• Serum testosterone often elevated

General Considerations

• Hirsutism is defined as cosmetically unacceptable terminal hair growth that appears in women in a male pattern

• The amount of hair growth deemed unacceptable depends on a woman's ethnicity and cultural norms

• The Ferriman-Gallwey score is used to grade hirsutism

  • Grades range from 0 (none) to 4 (severe) in nine areas of the body

  • Scores below 8 are considered mild hirsutism and normal variants

  • Scores 8-15 indicate moderate hirsutism

  • Scores over 15 indicate severe hirsutism

• Virilization is defined as the development of male physical characteristics in women, such as

  • Pronounced muscle development

  • Deep voice

  • Male pattern baldness

  • More severe hirsutism

Causes of hirsutism

• Idiopathic or familial—often hirsutism may be normal for genetic background

• Polycystic ovary syndrome

  • Accounts for at least 50% of all cases of hirsutism associated with elevated serum testosterone levels

  • Must meet three criteria

    • Androgen excess with clinical hyperandrogenism and/or elevated serum free or total testosterone

    • Ovarian dysfunction with oligoanovulation and/or polycystic ovary morphology

    • Absence of other causes of testosterone excess or anovulation such as pregnancy, thyroid dysfunction, 21-hydroxylase deficiency, neoplastic testosterone secretion, Cushing syndrome, or hyperprolactinemia

• Ovarian tumor (uncommon) and adrenal carcinoma (rare)

• Steroidogenic enzyme defects

  • ~2% of adult-onset hirsutism is due to partial defect in adrenal 21-hydroxylase

  • Rare patients with hyperandrogenism and hypertension have 11-hydroxylase deficiency

  • Patients with XY karyotype and deficiency of 17α-hydroxysteroid dehydrogenase-3 or 5α-reductase-2 may present as phenotypic girls in whom virilization develops at puberty

• Other rare causes of hirsutism and virilization

  • Acromegaly

  • ACTH-induced Cushing syndrome

  • Adrenal carcinoma

  • Genetic cortisol resistance

  • Porphyria cutanea tarda

  • Maternal virilization during pregnancy due to luteoma of pregnancy

  • Hyperreactio luteinalis

  • Diffuse stromal Leydig cell hyperplasia in postmenopausal women

  • Acquired hypertrichosis lanuginosa (diffuse fine hair growth on face and body in association with malignancy, especially colorectal cancer)

  • Pharmacologic causes

    • Minoxidil

    • Cyclosporine

    • Phenytoin

    • Anabolic steroids

    • Interferon

    • Cetuximab

    • Diazoxide

    • Certain progestins

Clinical Findings

Symptoms and Signs

• Increased sexual hair (chin, upper lip, abdomen, and chest)

• Acne due to increased sebaceous gland activity

• Menstrual irregularities, anovulation, and amenorrhea common

• Defeminization

  • Breast size decrease

  • Loss of feminine adipose tissue

• Virilization implicates presence of testosterone-producing neoplasm

  • Frontal balding

  • Muscularity

  • Clitoromegaly

  • Deepening of voice

• Hypertension is seen in rare conditions with Cushing syndrome, adrenal 11-hydroxylase deficiency, or cortisol resistance syndrome

• Ovarian enlargement may be cystic or neoplastic

• Polycystic ovary syndrome is associated with hypertension and hyperlipidemia

Diagnosis

Laboratory Tests

• Serum ...