What is the initial management step in a 58-year-old male with elevated total testosterone and Sex Hormone-Binding Globulin (SHBG) but normal free testosterone and hyperthyroidism?

Laboratory Evaluation for a 58-Year-Old Male with Elevated Total Testosterone, SHBG, Normal Free Testosterone, and Hyperthyroidism

The most important initial laboratory tests for this patient should include thyroid function tests (TSH, free T3, free T4), liver function tests, and prolactin level to evaluate the underlying causes of his hormone abnormalities.

Understanding the Relationship Between Hyperthyroidism and Sex Hormones

Hyperthyroidism significantly impacts sex hormone levels through several mechanisms:

• Thyroid hormone excess increases SHBG production in the liver, which binds testosterone and reduces free testosterone availability 1
• In hyperthyroidism, total testosterone is often elevated while free testosterone may be normal or low 2
• This pattern (high total testosterone, high SHBG, normal free testosterone) is characteristic of hyperthyroidism 3

Initial Laboratory Evaluation

First-line Tests:

• Complete thyroid function panel:
  • TSH (will be suppressed)
  • Free T3 and Free T4 (will be elevated)
  • Thyroid antibodies (TPO, TSH receptor antibodies) to determine etiology 4

Second-line Tests:

• Liver function tests (AST, ALT, GGT, bilirubin, albumin)

  • Liver dysfunction can affect SHBG production 5
  • Monitoring needed if antithyroid medications are started 6, 7

• Prolactin level

  • Hyperprolactinemia can occur with thyroid dysfunction 8
  • Important to rule out pituitary adenomas 8

• Complete blood count

  • Baseline before potential antithyroid therapy 6, 7
  • Monitor for potential agranulocytosis with treatment

Additional Testing Based on Clinical Context

• Hemoglobin/hematocrit

  • Important baseline before potential testosterone management 8
  • Elevated in hyperthyroidism and with testosterone therapy

• Estradiol level

  • Often elevated in men with hyperthyroidism 2
  • Important if patient has breast symptoms or gynecomastia 8

• Lipid profile

  • Hyperthyroidism affects lipid metabolism 8
  • Baseline before potential treatment

• Pituitary MRI

  • Consider if prolactin is elevated or if TSH is inappropriately normal/elevated
  • To rule out TSH-secreting pituitary adenoma 8

Monitoring and Follow-up

After initiating treatment for hyperthyroidism:

• Monitor thyroid function tests regularly
• Recheck testosterone (total and free) and SHBG after thyroid function normalizes
• Sex hormone abnormalities typically resolve with successful treatment of hyperthyroidism 1

Important Clinical Considerations

• The pattern of elevated total testosterone with normal free testosterone in this patient is likely secondary to hyperthyroidism rather than primary gonadal pathology 3
• Treating the underlying hyperthyroidism should normalize SHBG and total testosterone levels 1
• Avoid initiating testosterone replacement therapy until hyperthyroidism is controlled and hormone levels are reassessed 9
• Monitor for cardiac complications, especially in patients over 50 years, as cardiovascular complications are the chief cause of death after treatment of hyperthyroidism 8

Common Pitfalls to Avoid

• Pitfall #1: Focusing on testosterone abnormalities before addressing the hyperthyroidism
• Pitfall #2: Relying solely on total testosterone without measuring free testosterone and SHBG 5
• Pitfall #3: Failing to consider pituitary pathology (TSH-secreting adenoma) in cases with discordant thyroid function tests 8
• Pitfall #4: Starting testosterone replacement without first treating hyperthyroidism 9

Following resolution of hyperthyroidism, sex hormone levels should be reassessed, as they typically normalize with successful treatment of thyroid dysfunction.