What is the interpretation of a 19-39 year old non-obese adult male's hormonal panel showing total testosterone (513.2 ng/dL), free testosterone (6.9 pg/mL), luteinizing hormone (LH) (5.1 mIU/mL), follicle-stimulating hormone (FSH) (4.9 mIU/mL), slightly elevated prolactin (13.4 ng/mL), and low prostate-specific antigen (PSA) (0.5 ng/mL)?

Hormonal Panel Interpretation: Normal Testosterone with Low Free Testosterone

This hormonal panel reveals functional hypogonadism due to elevated SHBG (48.6 nmol/L), which binds testosterone and reduces bioavailable hormone despite normal total testosterone (513.2 ng/dL), explaining potential symptoms of androgen deficiency. 1

Key Laboratory Findings

The critical issue is the low free testosterone (6.9 pg/mL) in the context of normal total testosterone, indicating that SHBG is sequestering most testosterone in an inactive bound form. 1 This pattern of functional hypogonadism is frequently missed when only total testosterone is measured, as it misses approximately half of hypogonadism diagnoses when SHBG is elevated. 1

Gonadotropin Assessment

• LH (5.1 mIU/mL) and FSH (4.9 mIU/mL) are in the normal range, indicating intact hypothalamic-pituitary-gonadal axis function without primary testicular failure or secondary hypogonadism. 2
• The normal LH with low free testosterone suggests the pituitary is not adequately compensating for the reduced bioavailable testosterone. 1

Prolactin Evaluation

• Prolactin (13.4 ng/mL) is within normal limits and does not require further evaluation at this level. 2
• According to AUA guidelines, prolactin measurement is indicated when testosterone is low AND LH is low or low-normal, which does not apply here. 2
• Elevated prolactin can disrupt the hypothalamic-pituitary-gonadal axis and lower testosterone, but this patient's prolactin is normal. 3, 4

PSA Assessment

• PSA (0.5 ng/mL) is appropriately low for this age group and requires no intervention. 2
• This level is well below the 4.0 ng/mL threshold that would prompt prostate biopsy consideration. 2

Clinical Significance of Elevated SHBG

The free testosterone index (total testosterone/SHBG ratio) is more predictive of hypogonadal symptoms than total testosterone alone, with a ratio <0.3 indicating functional hypogonadism. 1 In this case, the ratio would need to be calculated to confirm functional hypogonadism.

Expected Symptoms

• Low libido, erectile dysfunction, reduced muscle mass, and fatigue can all occur despite normal total testosterone when SHBG is elevated, as free testosterone is the bioactive form driving sexual function and tissue effects. 1
• Only free testosterone can enter tissues and exert physiological effects critical for maintaining sexual function, muscle mass, and energy levels. 1

Diagnostic Next Steps

Confirm functional hypogonadism by measuring calculated free testosterone using equilibrium dialysis on a repeat morning blood draw. 1 Single measurements can be misleading, and repeat testing is necessary to confirm the pattern. 1

Investigate Causes of Elevated SHBG

• Check thyroid function (TSH, free T4) to exclude hyperthyroidism, which increases SHBG production. 1
• Perform liver function tests to exclude chronic liver disease as a cause of elevated SHBG. 1
• Review medications including oral estrogens, anticonvulsants, and other SHBG-elevating drugs. 1
• Assess metabolic health including insulin resistance and body composition, as low insulin states can increase SHBG. 1

Management Algorithm

First-Line Approach

Address reversible causes of elevated SHBG before considering testosterone replacement therapy. 1

• Treat hyperthyroidism if present. 1
• Discontinue medications that increase SHBG when possible. 1
• Optimize metabolic health and body composition. 1

Second-Line Approach

If free testosterone remains low after addressing reversible causes, testosterone replacement therapy may be considered. 1

• Transdermal testosterone preparations are preferred for most patients due to stable day-to-day levels. 1
• Testosterone replacement can improve sexual function with moderate-certainty evidence, producing small to moderate improvements in global sexual function and erectile function. 1
• Monitor free testosterone levels 2-3 months after initiation of therapy to ensure adequate replacement. 1

Monitoring During Treatment

If testosterone replacement is initiated, follow AUA monitoring recommendations: 2

• Assess efficacy with dosage adjustment for suboptimal response at 1-2 months. 2
• Perform monitoring evaluation with repeated testing every 3-6 months for the first year and annually thereafter. 2
• Monitor testosterone, hematocrit/hemoglobin, and PSA levels. 2
• Perform digital rectal examination annually. 2
• Consider prostate biopsy if PSA rises above 4.0 ng/mL or increases by more than 1.0 ng/mL in the first 6 months, or by more than 0.4 ng/mL/year thereafter. 2

Common Pitfalls to Avoid

Do not rely on total testosterone alone when SHBG is elevated, as this misses approximately half of functional hypogonadism diagnoses. 1 Always measure free testosterone by equilibrium dialysis to confirm the diagnosis. 1

Do not initiate testosterone replacement without first investigating and addressing reversible causes of elevated SHBG, as treating the underlying condition may normalize free testosterone without requiring exogenous hormone therapy. 1