What are the initial lab tests for diagnosing hypogonadism?

Initial Laboratory Tests for Diagnosing Hypogonadism

The initial laboratory evaluation for diagnosing hypogonadism should include morning total testosterone levels measured on at least two separate days, free testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). 1

Core Laboratory Panel

Essential Tests

• Morning total testosterone (between 8-10 AM) on at least two separate occasions 2, 1, 3
• Free testosterone (preferably by equilibrium dialysis) 2, 1
• Sex hormone-binding globulin (SHBG) 2
• Luteinizing hormone (LH) 2, 1
• Follicle-stimulating hormone (FSH) 2, 1

Additional Baseline Tests

• Complete blood count (to establish baseline hematocrit) 1
• Prostate-specific antigen (PSA) (for men over 40 years) 1

Interpretation Algorithm

1. Confirm testosterone deficiency:

   • Total testosterone < 300 ng/dL (10.4 nmol/L) on two morning measurements 1, 4
   • Free testosterone index (total testosterone/SHBG ratio) < 0.3 indicates hypogonadism 2

2. Determine type of hypogonadism:

   • Primary hypogonadism: Low testosterone + elevated LH/FSH 2, 5
   • Secondary hypogonadism: Low testosterone + low or normal LH/FSH 2, 5
   • Mixed/Compensated: Normal testosterone + elevated LH 2

Special Considerations

Obesity

• In obese patients, free testosterone measurement is essential as obesity decreases SHBG, potentially masking hypogonadism when only total testosterone is measured 2
• Morning free testosterone by equilibrium dialysis should be frankly low on at least 2 separate assessments 2

Timing

• Serum for testosterone levels should be taken in the morning due to significant diurnal variation 2, 1
• If initial results are borderline (total testosterone 8-12 nmol/L or 231-346 ng/dL), repeat testing is recommended 6

Additional Testing Based on Initial Results

If hypogonadism is confirmed and secondary (hypogonadotropic) in nature:

• Serum prolactin 2, 1
• Iron saturation (to rule out hemochromatosis) 2
• Thyroid function tests 2
• Pituitary function testing 2
• Consider MRI of sella turcica if secondary hypogonadism is confirmed 2

Common Pitfalls to Avoid

1. Single testosterone measurement: Relying on a single measurement rather than confirming with at least two morning samples can lead to misdiagnosis 1, 3

2. Ignoring time of day: Failing to draw testosterone in the morning (8-10 AM) when levels are highest 2, 1

3. Overlooking free testosterone: Especially important in obesity, where total testosterone may be misleadingly low due to reduced SHBG 2

4. Missing secondary causes: Not measuring LH/FSH to distinguish between primary and secondary hypogonadism 2, 5

5. Inadequate clinical correlation: Laboratory diagnosis must be correlated with symptoms of hypogonadism including sexual dysfunction, fatigue, reduced muscle mass, and cognitive changes 1, 6

By following this systematic approach to laboratory testing for hypogonadism, clinicians can accurately diagnose the condition and determine its etiology, leading to appropriate treatment decisions that will improve patient morbidity, mortality, and quality of life.