Can a 42-year-old man with total testosterone 370 ng/dL, free testosterone 121 pg/mL, DHEA‑S 290 µg/dL, and SHBG 10.3 nmol/L be diagnosed with testicular hypofunction?

Can This Patient Be Diagnosed with Testicular Hypofunction?

No, this patient cannot be diagnosed with testicular hypofunction (primary hypogonadism) based on the laboratory values provided, and the diagnosis of hypogonadism itself is questionable without confirmatory testing and symptom assessment.

Critical Diagnostic Issues with This Case

Incomplete Diagnostic Workup

The most glaring problem is the absence of LH and FSH measurements, which are absolutely required to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism 1. Without these gonadotropin levels, you cannot determine whether this represents testicular failure or central hypogonadism 2.

• Primary hypogonadism (testicular dysfunction) shows elevated LH/FSH with low testosterone 1
• Secondary hypogonadism shows low or low-normal LH/FSH with low testosterone 1
• This distinction has critical treatment implications, particularly for fertility preservation 2

Borderline Testosterone Levels Require Confirmation

Total testosterone of 370 ng/dL is borderline-low, not definitively low 1. The 2025 European Association of Urology guidelines require:

• Two separate morning testosterone measurements (8-10 AM) below 300 ng/dL to establish biochemical hypogonadism 1, 2
• This patient's single measurement of 370 ng/dL falls above the diagnostic threshold 1
• Repeat morning testing is mandatory due to assay variability and diurnal fluctuation 2, 3

Free Testosterone Discordance Suggests Measurement Error

The reported free testosterone of 121 pg/mL appears inconsistent with the total testosterone and SHBG values 4, 5. With:

• Total testosterone: 370 ng/dL
• SHBG: 10.3 nmol/L (markedly low)
• Expected free testosterone should be elevated, not low 4

Low SHBG (10.3 nmol/L) means less testosterone is bound, so free testosterone should be higher than normal, not lower 4, 5. This discordance suggests:

• Laboratory error in free testosterone measurement 3
• Free testosterone should be measured by equilibrium dialysis (gold standard) or calculated using the Vermeulen formula 2, 4, 3
• Direct immunoassay measurements of free testosterone are notoriously unreliable 3

What This Patient Actually Needs

Step 1: Confirm Biochemical Hypogonadism

Repeat morning total testosterone (8-10 AM) on at least one additional occasion 1, 2:

• If both measurements are <300 ng/dL, biochemical hypogonadism is confirmed 1, 2
• If either measurement is ≥300 ng/dL, hypogonadism is not confirmed 1

Measure free testosterone by equilibrium dialysis or calculate it using total testosterone, SHBG, and albumin 2, 4, 3:

• With SHBG of 10.3 nmol/L (low), calculated free testosterone should be elevated 4
• If calculated free testosterone is normal or high despite borderline total testosterone, this represents functional hypogonadism from low SHBG, not true androgen deficiency 2

Step 2: Measure Gonadotropins to Determine Type

Once low testosterone is confirmed, measure LH and FSH 1, 2:

• Elevated LH/FSH = primary hypogonadism (testicular dysfunction) 1
• Low or low-normal LH/FSH = secondary hypogonadism (hypothalamic-pituitary dysfunction) 1

Step 3: Assess Symptoms

Hypogonadism requires BOTH biochemical evidence AND specific symptoms 1:

• Primary symptoms warranting treatment: diminished libido and erectile dysfunction 1, 2
• Secondary symptoms with weaker evidence: diminished sense of vitality, though improvements are minimal 2
• No proven benefit for: fatigue, low energy, physical functioning, depressed mood, or cognitive complaints 2

Why the DHEA-S Value Doesn't Help

DHEA-S of 290 µg/dL provides no diagnostic value for hypogonadism 1:

• DHEA-S is produced by the adrenal glands, not the testes 1
• It does not distinguish primary from secondary hypogonadism 1
• It should not influence the diagnostic workup 1

Common Pitfalls to Avoid

Never diagnose hypogonadism based on a single testosterone measurement 1, 2:

• Testosterone levels fluctuate significantly due to diurnal variation, assay variability, and biological factors 3
• Two morning measurements are required 1, 2

Never diagnose hypogonadism based on symptoms alone without confirmed low testosterone 1, 2:

• Symptoms of hypogonadism are non-specific and overlap with many other conditions 1, 6
• Approximately 20-30% of men receiving testosterone in the US do not have documented low testosterone before treatment initiation 2

Never skip gonadotropin measurement (LH/FSH) 1, 2:

• The distinction between primary and secondary hypogonadism is critical for treatment selection and fertility preservation 2
• Men with secondary hypogonadism can potentially achieve both fertility restoration and normal testosterone with gonadotropin therapy 2
• Testosterone therapy is absolutely contraindicated in men seeking fertility preservation 1, 2

Never trust direct immunoassay measurements of free testosterone 3:

• Free testosterone should be measured by equilibrium dialysis or calculated using validated formulas 2, 4, 3
• The reported free testosterone of 121 pg/mL is inconsistent with the low SHBG and should be rechecked 4, 5

Clinical Algorithm for This Patient

1. Repeat morning total testosterone (8-10 AM) 1, 2
2. Calculate free testosterone using total testosterone, SHBG, and albumin (Vermeulen formula) 2, 4
3. If both total testosterone measurements are <300 ng/dL, measure LH and FSH 1, 2
4. Assess for specific symptoms: diminished libido, erectile dysfunction 1, 2
5. Only if BOTH biochemical hypogonadism AND symptoms are confirmed, consider treatment 1

Bottom line: This patient needs proper diagnostic confirmation before any diagnosis of hypogonadism—primary or secondary—can be made 1, 2.