What additional laboratory tests are recommended for patients with low total testosterone levels?

Additional Laboratory Tests for Low Total Testosterone Levels

When a patient presents with low total testosterone levels, additional laboratory tests should include morning repeat total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, sex hormone-binding globulin (SHBG), free or bioavailable testosterone, complete blood count, and prostate-specific antigen (PSA) for men over 40. 1

Confirming Low Testosterone

1. Morning Repeat Total Testosterone

   • Testosterone levels should be measured in the morning (between 7 am and 12 pm) when levels are typically highest 1, 2
   • Studies show only 9% of testosterone tests are performed during the recommended morning hours, highlighting a significant compliance issue 2
   • Repeat testing is essential as testosterone levels can fluctuate significantly

2. Free or Bioavailable Testosterone

   • When total testosterone results are equivocal (8-12 nmol/L or approximately 230-350 ng/dL), measurement of free or bioavailable testosterone is recommended 1, 3
   • Free testosterone measurement by equilibrium dialysis is the most reliable method, though less commonly available 4
   • Calculated free testosterone using Vermeulen's equation is an acceptable alternative 5

Determining the Cause of Hypogonadism

1. Pituitary Function Tests

   • Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH)

     • Helps differentiate between primary (testicular) and secondary (pituitary/hypothalamic) hypogonadism 1, 5
     • Low/normal LH and FSH with low testosterone suggests secondary hypogonadism
     • Elevated LH and FSH with low testosterone indicates primary hypogonadism

   • Prolactin

     • Elevated prolactin can cause secondary hypogonadism
     • Essential to rule out prolactinoma and other pituitary disorders 1

2. Sex Hormone-Binding Globulin (SHBG)

   • SHBG levels affect the interpretation of total testosterone results 6
   • Conditions like obesity, diabetes, hypothyroidism, and certain medications can alter SHBG levels
   • Useful for calculating free testosterone when direct measurement is unavailable

Associated Health Assessment

1. Metabolic and Cardiovascular Assessment

   • Fasting glucose and HbA1c

     • Type 2 diabetes is associated with hypogonadism 5
     • 41% of men with type 2 diabetes may have hypogonadism compared to 10% of non-diabetic men 5

   • Lipid profile

     • Recommended due to association between hypogonadism and metabolic syndrome 1

2. Hematologic Assessment

   • Complete Blood Count (CBC)
     • Establishes baseline hemoglobin and hematocrit
     • Critical for monitoring during testosterone replacement therapy as hematocrit >54% is a safety concern 1

3. Prostate Health Assessment

   • Prostate-Specific Antigen (PSA)
     • Recommended for men over 40 years before initiating testosterone therapy 1
     • Establishes baseline for monitoring during treatment

Common Pitfalls and Caveats

• Laboratory Reference Range Variability

  • Reference ranges for testosterone vary widely between laboratories
  • The lower reference value for total testosterone can range from 130 to 450 ng/dL (350% difference) 4
  • Always interpret results in the context of the specific laboratory's reference range

• Timing of Blood Collection

  • Failure to collect morning samples is a major pitfall in testosterone testing 2
  • Morning collection is essential for accurate assessment

• Reliance on Total Testosterone Alone

  • Total testosterone may be misleading in conditions that affect SHBG levels
  • Free or bioavailable testosterone provides additional clarity in equivocal cases 6, 3

• Ignoring Clinical Symptoms

  • Diagnosis of hypogonadism requires both biochemical evidence and clinical symptoms 3, 5
  • Laboratory values alone are insufficient for diagnosis

By following this comprehensive testing approach, clinicians can accurately diagnose the presence and cause of hypogonadism, establish important baseline values for monitoring therapy, and identify associated conditions that may require additional management.