Differential Diagnoses of Hirsutism
The differential diagnosis of hirsutism includes polycystic ovary syndrome (PCOS) as the most common cause (70-80% of cases), followed by idiopathic hirsutism, nonclassical congenital adrenal hyperplasia (21-hydroxylase deficiency), androgen-secreting tumors, functional hypothalamic amenorrhea with polycystic ovarian morphology, Cushing's syndrome, hyperprolactinemia, acromegaly, and drug-induced hyperandrogenism. 1, 2, 3
Primary Endocrine Causes
Polycystic Ovary Syndrome (PCOS)
- PCOS accounts for the vast majority of hirsutism cases, representing the most common cause of androgen excess 1, 4, 3
- Diagnosed using Rotterdam criteria requiring 2 of 3 findings: hyperandrogenism (clinical or biochemical), ovulatory dysfunction, or polycystic ovary morphology 5, 6
- In adolescent females, PCOS diagnosis requires hyperandrogenism plus persistent oligomenorrhea 5
- Associated features include infrequent menses, androgenetic alopecia, infertility, clitoromegaly, and truncal obesity 5
Idiopathic Hirsutism
- Affects 5-17% of hirsute patients depending on ethnicity and geographic area 3, 7
- Diagnosis requires normal ovulatory function AND normal circulating androgen levels 1, 7
- Regular menses alone are insufficient to exclude ovulatory dysfunction, as up to 40% of eumenorrheic hirsute women are anovulatory 7
- Pathophysiology involves primary increase in skin 5α-reductase activity and possibly altered androgen receptor function 7
Nonclassical Congenital Adrenal Hyperplasia (NCCAH)
- Accounts for 1-8% of hirsute women, primarily due to 21-hydroxylase deficiency 3
- Can present with recalcitrant acne in both men and women 5
- In prepubertal children, look for early-onset body odor, axillary/pubic hair, accelerated growth, advanced bone age, and genital maturation 5
Neoplastic Causes
Androgen-Secreting Tumors (Ovarian or Adrenal)
- Life-threatening potential requires prompt identification 4, 3
- Serum testosterone >200 ng/dL is highly suggestive of adrenal or ovarian tumor 2
- Adrenocortical carcinomas may present with virilization including hirsutism, deepening of voice, and oligo/amenorrhea in women 5
- Suspect malignancy if tumor has irregular morphology, is lipid-poor, does not wash out on contrast-enhanced CT, is >3 cm, or secretes multiple hormones 5
Other Endocrine Disorders
Cushing's Syndrome
- Presents with weight gain, proximal muscle weakness, hypertension, psychiatric disturbances, hirsutism, centripetal obesity, purple striae, buffalo hump, hyperglycemia, and hypokalemia 5
- Requires specific surgical treatment when identified 4, 3
Hyperprolactinemia
- Must be excluded in the diagnostic workup of hirsutism 4, 3
- Part of the differential diagnosis of PCOS 5
Acromegaly
Thyroid Disease
- Part of the differential diagnosis of PCOS and hyperandrogenism 5
Functional Hypothalamic Amenorrhea with PCOM
- Can easily be misclassified as PCOS phenotype D (PCOM plus oligo/anovulation) 5
- Distinguished by history of weight loss, vigorous exercise, or stress 5
- Lower serum levels of estradiol, androgens, LH, and AMH compared to PCOS 5
- Higher SHBG levels than PCOS 5
- Low insulin levels and normal insulin sensitivity, contrasting with insulin resistance in PCOS 5
Drug-Induced Hirsutism
Rare Causes
- Glucocorticoid resistance syndrome 3
- Hyperandrogenic-insulin-resistant acanthosis nigricans (HAIR-AN) syndrome affects approximately 3% of hyperandrogenic women 3
Critical Diagnostic Considerations
The most important purpose of investigation is identifying women with potentially life-threatening pathologies, particularly androgen-secreting tumors 4, 3. A systematic approach should assess for features suggesting specific etiologies: