How to Diagnose Secondary Hypogonadism: Essential Tests & Evaluations

Quick Summary

• Low testosterone with normal testicular size points to secondary hypogonadism.
• Start with serum total and free testosterone, then check LH, FSH, and prolactin.
• Typical lab pattern: low testosterone + low or inappropriately normal LH/FSH.
• If labs suggest a pituitary issue, order a pituitary MRI.
• Use the step‑by‑step algorithm to avoid misdiagnosis and unnecessary referrals.

When a man shows low testosterone but the pituitary gland is the problem, that's secondary hypogonadism is a condition where the testes produce insufficient testosterone because of inadequate signaling from the brain’s hypothalamic‑pituitary axis. It’s different from primary hypogonadism, where the testes themselves are damaged. Spotting the right condition early saves time, prevents costly tests, and gets patients on the right therapy faster.

What Triggers the Need for an Evaluation?

Typical clues include:

• Persistent fatigue, low libido, or erectile dysfunction despite a normal health check.
• Weight gain, reduced muscle mass, or increased body fat.
• Blood tests that show total testosterone below 300 ng/dL (8.7 nmol/L) on at least two morning samples.
• No clear cause like chronic steroids, opioids, or severe illness.

If any of these ring a bell, it’s time to start the diagnostic work‑up.

First‑Line Hormone Tests

The backbone of the work‑up is a panel of blood tests. Below are the key players:

• Testosterone is the main male sex hormone that drives libido, muscle growth, and bone health. Measure total testosterone in the early morning (7‑10am). If total is borderline, calculate free testosterone or use equilibrium dialysis.
• Luteinizing Hormone (LH) is the pituitary hormone that tells the testes to crank out testosterone. Low or normal LH with low testosterone suggests a central problem.
• Follicle‑stimulating Hormone (FSH) is another pituitary hormone that mainly supports sperm production. In secondary hypogonadism, FSH follows the same pattern as LH.
• Prolactin is a hormone that, when elevated, can suppress GnRH and consequently LH/FSH. Elevated prolactin flags a possible prolactinoma.

Most labs also include sex hormone‑binding globulin (SHBG) because it influences free testosterone calculations.

Interpreting the Lab Results

Typical Hormone Patterns in Secondary vs. Primary Hypogonadism

Hormone	Secondary (Central) Pattern	Primary (Testicular) Pattern
Total Testosterone	Low	Low
Free Testosterone	Low	Low
LH	Low or Inappropriately Normal	High
FSH	Low or Inappropriately Normal	High
Prolactin	Normal or Elevated (if prolactinoma)	Normal

When LH and FSH are low while testosterone is low, the diagnosis leans toward secondary hypogonadism. An isolated low testosterone with high LH/FSH points to a primary testicular issue.

When to Move Beyond Blood Work: Imaging

If the hormone panel suggests a central problem, the next step is imaging the pituitary region. The gold standard is a contrast‑enhanced MRI.

• MRI is a magnetic resonance imaging technique that provides detailed pictures of soft tissue, including the pituitary gland. Look for micro‑adenomas (<10mm) or larger sellar masses.
• If MRI is normal but symptoms persist, consider a dynamic pituitary function test (GnRH stimulation) to unmask subtle deficiencies.

Finding a pituitary tumor changes management dramatically-often surgery or medication (e.g., dopamine agonists for prolactinomas) is required before hormone replacement.

Putting It All Together: A Step‑by‑Step Diagnostic Algorithm

1. Take a thorough history focusing on sexual symptoms, energy levels, and medication use.
2. Perform a physical exam-note testicular volume, body hair distribution, and any visual field deficits.
3. Order morning total testosterone, free testosterone, LH, FSH, prolactin, and SHSH (optional).
4. Interpret labs using the table above.
   • If LH/FSH are low → suspect secondary.
   • If LH/FSH are high → primary; consider genetic or autoimmune causes.
5. For secondary pattern, repeat testosterone measurement in 2-4 weeks to confirm chronicity.
6. Order pituitary MRI if labs remain consistent with central dysfunction.
7. Refer to endocrinology when:
   • MRI shows a lesion.
   • Prolactin >30ng/mL.
   • Patient has visual disturbances or severe headaches.
8. Begin testosterone replacement only after confirming the diagnosis and ruling out contraindications (e.g., untreated prostate cancer).

Following this flow cuts down on unnecessary scans and speeds up treatment initiation.

Common Pitfalls & Red Flags

• Relying on a single testosterone draw-morning levels fluctuate, and stress can suppress results.
• Ignoring an elevated prolactin; a treatable prolactinoma can masquerade as secondary hypogonadism.
• Overlooking medications like glucocorticoids, opioids, or GnRH analogs that can suppress the axis.
• Skipping the physical exam-small testicular size suggests primary cause.

Spotting these early prevents misclassification and inappropriate hormone therapy.

Quick Checklist for Clinicians

• Ask about libido, energy, and mood.
• Measure total & free testosterone in the early morning.
• Include LH, FSH, and prolactin in the initial panel.
• Confirm low testosterone with a second morning draw.
• Interpret LH/FSH pattern to differentiate primary vs. secondary.
• Order pituitary MRI if central pattern is present.
• Refer to endocrinology for pituitary lesions, high prolactin, or unclear cases.

Frequently Asked Questions

By following a systematic approach-history, targeted labs, and appropriate imaging-you can confidently distinguish secondary hypogonadism from primary causes and get patients on the right treatment path.