What is the appropriate workup for hypergonadism (excessive production of sex hormones)?

Workup of Hypergonadism

The appropriate workup for hypergonadism requires a systematic approach with specific laboratory testing based on gender, clinical presentation, and suspected etiology to identify the underlying cause and guide appropriate treatment.

Initial Assessment

Clinical Evaluation

• Assess for signs and symptoms of sex hormone excess:
  • In females: hirsutism, acne, deepening of voice, clitoromegaly, menstrual irregularities, virilization 1
  • In males: gynecomastia, testicular atrophy, infertility, breast symptoms 2
  • In both: rapid onset of symptoms may suggest tumor etiology

Laboratory Testing

For Female Hypergonadism:

1. Baseline hormone measurements:

   • Total and free testosterone
   • DHEA-S (dehydroepiandrosterone sulfate)
   • Androstenedione
   • 17-hydroxyprogesterone (to rule out congenital adrenal hyperplasia) 3
   • Estradiol levels if estrogen excess suspected

2. Pituitary function assessment:

   • LH and FSH levels to distinguish primary vs. secondary hypergonadism
   • Prolactin levels (especially with oligomenorrhea) 1

3. Adrenal function assessment:

   • 24-hour urinary free cortisol or overnight dexamethasone suppression test (if Cushing's syndrome suspected) 1
   • Two-day dexamethasone suppression test (to differentiate PCOS from non-classical congenital adrenal hyperplasia) 1

For Male Hypergonadism:

1. Baseline hormone measurements:

   • Total and free testosterone (morning samples between 8-10 AM) 2
   • Estradiol (especially with gynecomastia) 2
   • Sex hormone-binding globulin (SHBG) 2

2. Pituitary function assessment:

   • LH and FSH levels to determine primary vs. secondary hypergonadism 2
   • Prolactin levels (especially with low/normal LH and low testosterone) 2, 4

3. Additional testing based on presentation:

   • Semen analysis if fertility is a concern 2
   • Hemoglobin/hematocrit 2

Specialized Testing Based on Initial Results

For Primary Hypergonadism (High LH/FSH):

• Karyotype testing and Y-chromosome analysis for microdeletions in males with severe oligospermia or azoospermia 2
• Reproductive health evaluation for fertility concerns 2

For Secondary Hypergonadism (Low/Normal LH/FSH):

• Pituitary imaging:
  • MRI of sella turcica if prolactin is elevated or if testosterone is <150 ng/dL with low/normal LH 2
  • Evaluate for pituitary adenomas or other structural abnormalities 4

For Suspected Adrenal Causes:

• Adrenal imaging:

  • Non-contrast CT as first-line imaging for adrenal masses 2
  • Washout CT or chemical-shift MRI for indeterminate adrenal masses 2

• Adrenal function tests:

  • Aldosterone-to-renin ratio if hypertension or hypokalemia present 2
  • Plasma or 24-hour urinary metanephrines if pheochromocytoma suspected 2

Special Considerations

For Suspected Tumor Etiology:

• Rapid onset of severe hyperandrogenism with very high hormone levels suggests androgen-secreting tumor 1
• Adrenal vein sampling may be necessary to localize aldosterone-producing adenomas 2
• Avoid routine adrenal mass biopsy 2

For Adolescents:

• Differentiate between physiologic hyperandrogenism of puberty and pathologic causes 3
• Evaluate body mass index, blood pressure, and signs of hyperandrogenism 3
• Consider PCOS in adolescents with persistent symptoms beyond normal puberty 3

Common Pitfalls to Avoid

1. Failure to distinguish primary from secondary hypergonadism:

   • Always measure LH/FSH levels to determine the origin of hypergonadism 2, 4

2. Overlooking non-endocrine causes:

   • Consider medications, supplements, or exogenous hormone use

3. Missing rare but serious etiologies:

   • Androgen-secreting tumors are rare but should be considered with rapid onset of severe symptoms 1
   • Pituitary adenomas may require specific imaging studies 2

4. Inadequate follow-up:

   • Patients with indeterminate findings require appropriate follow-up imaging and testing 2

5. Not considering multidisciplinary management:

   • Complex cases benefit from endocrinology, radiology, and surgical consultation 2

By following this systematic approach to the workup of hypergonadism, clinicians can effectively identify the underlying cause and develop appropriate treatment strategies to address both the hormonal imbalance and any associated complications.