What is the most likely diagnosis for a patient with primary amenorrhea, normal adult-size breasts, coarse pubic and axillary hair, and hyperandrogenism (elevated testosterone level)?

Most Likely Diagnosis: Complete Androgen Insensitivity Syndrome (CAIS)

The most likely diagnosis is Complete Androgen Insensitivity Syndrome (CAIS) - Option B. This patient presents with the classic triad of primary amenorrhea, normal breast development, and markedly elevated testosterone (13.86 nmol/L, nearly 5 times the upper limit of normal), but with coarse pubic and axillary hair, which requires careful interpretation.

Clinical Reasoning

Why CAIS is Most Likely

• Primary amenorrhea with normal breast development indicates the presence of estrogen but absence of a functional uterus or endometrial response 1
• Markedly elevated testosterone (13.86 nmol/L vs normal 0.7-2.8 nmol/L) in the setting of primary amenorrhea points to either androgen insensitivity or an androgen-producing condition 1
• In CAIS, patients have 46,XY karyotype with testes that produce testosterone, but complete androgen receptor dysfunction prevents virilization while allowing aromatization of testosterone to estrogen, resulting in normal female breast development 1

The Pubic/Axillary Hair Paradox

• This is the key clinical nuance: Classic teaching states CAIS patients have absent or sparse pubic/axillary hair due to complete androgen insensitivity 1
• However, the presence of "coarse" hair in this case may represent:
  • Partial rather than complete insensitivity (though this would typically show some virilization)
  • Adrenal androgen contribution (DHEAS-mediated hair growth can occur independently of testosterone receptor function) 2
  • Individual variation in the clinical presentation 1

Why Other Options Are Less Likely

Option A: Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome

• MRKH presents with primary amenorrhea and normal breast development, BUT testosterone levels are normal female range (0.7-2.8 nmol/L), not elevated 1
• The markedly elevated testosterone (13.86 nmol/L) essentially excludes this diagnosis 1

Option C: Asherman's Syndrome

• Asherman's syndrome causes secondary amenorrhea (acquired intrauterine adhesions), not primary amenorrhea 1
• Requires prior uterine instrumentation or infection 1
• This diagnosis is incompatible with the clinical presentation 1

Option D: Turner Syndrome

• Turner syndrome (45,XO) presents with primary amenorrhea but with absent or poor breast development due to ovarian dysgenesis and estrogen deficiency 1
• Testosterone levels would be low-normal, not markedly elevated 1
• The normal breast development excludes this diagnosis 1

Diagnostic Approach

Essential Next Steps

• Karyotype analysis to confirm 46,XY in suspected CAIS 1
• Pelvic ultrasound or MRI to identify absent uterus and presence of intra-abdominal or inguinal testes 1
• Repeat testosterone measurement using LC-MS/MS methodology in the morning for confirmation 2, 1
• LH and FSH levels (typically elevated in CAIS due to lack of negative feedback) 1

Critical Pitfall to Avoid

• Do not assume all CAIS patients have completely absent body hair - there is phenotypic variation, and adrenal androgens can contribute to hair growth independently of testosterone receptor function 2, 1
• The presence of pubic/axillary hair should not exclude CAIS when other features (primary amenorrhea, normal breasts, markedly elevated testosterone) strongly suggest this diagnosis 1

Management Implications

• Gonadectomy is recommended after completion of puberty due to 25-50% risk of malignant transformation of undescended testes 1
• Psychological support and counseling regarding diagnosis, fertility implications, and gender identity 1
• Hormone replacement therapy with estrogen after gonadectomy to maintain bone health and prevent menopausal symptoms 1