What is the diagnosis and treatment for a patient with hypergonadism (high serum testosterone), normal Luteinizing Hormone (LH), and hyperfolliculism (high Follicle-Stimulating Hormone (FSH))?

Diagnosis and Treatment of High Testosterone with Normal LH and High FSH

The most likely diagnosis for a patient with high serum testosterone, normal LH, and high FSH is a gonadotropin-secreting pituitary adenoma, which requires MRI imaging of the pituitary and referral to endocrinology for further evaluation and treatment. 1, 2, 3

Diagnostic Approach

Laboratory Confirmation

• Verify hormone profile with repeat testing:
  • Morning total and free testosterone levels
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
  • Sex hormone-binding globulin (SHBG)
  • Dehydroepiandrosterone sulfate (DHEAS) 1

Clinical Assessment

• Evaluate for:
  • Testicular enlargement (a key finding in gonadotropin-secreting adenomas)
  • Sexual dysfunction despite high testosterone
  • Fertility status
  • Visual field defects (if macroadenoma present)
  • Headaches 1, 3

Imaging

• MRI of the brain with pituitary/sellar cuts (with and without contrast) is essential to identify pituitary adenoma 4, 1

Differential Diagnosis

1. Gonadotropin-secreting pituitary adenoma

   • Most likely diagnosis when seeing high FSH with normal LH and high testosterone
   • Often presents with testicular enlargement due to FSH stimulation 2, 3
   • May have normal sexual function despite hormonal abnormalities 3

2. Partial androgen resistance syndrome

   • Can present with elevated testosterone and variable gonadotropin levels
   • Usually has signs of undervirilization

3. Testicular tumor

   • Can produce both testosterone and gonadotropins
   • Physical examination and testicular ultrasound would be needed

Treatment Approach

For Confirmed Pituitary Adenoma

1. Surgical Management

   • Transsphenoidal surgery is first-line for macroadenomas causing mass effect 2
   • May be followed by radiation therapy for residual tumor 2

2. Medical Management

   • GnRH agonists (e.g., D-Trp6-LRH) can reduce FSH and LH levels and may shrink tumor size 2
   • Consider antiandrogens if testosterone levels remain elevated and symptomatic 1

3. Monitoring

   • Regular follow-up with hormone measurements every 3-6 months initially, then annually
   • Repeat MRI imaging to assess tumor size
   • Monitor for development of other pituitary hormone deficiencies 1

Important Considerations

• Unlike typical hypogonadism patterns, this presentation represents a paradoxical state of hypergonadotropism with hypergonadism
• Inhibin levels may be elevated in these patients, which can serve as a biochemical marker for gonadotropin-secreting tumors 3
• Testicular enlargement is a key physical finding that distinguishes this condition from primary testicular failure (which also presents with high FSH but has small testes) 3
• Even after successful surgery, hormonal abnormalities may persist, requiring ongoing medical management 2

Pitfalls to Avoid

• Don't assume primary testicular failure based solely on elevated FSH; check testicular size and testosterone levels
• Don't miss evaluating pituitary function comprehensively, as other hormonal axes may be affected
• Don't delay imaging when this hormone pattern is identified, as pituitary adenomas require prompt evaluation
• Don't confuse this condition with testosterone abuse/supplementation, which would suppress gonadotropins rather than elevate FSH