In a 27-year-old man with low‑normal total and free testosterone, elevated prolactin, slightly suppressed follicle‑stimulating hormone, normal luteinising hormone, normal estradiol and PSA, and mildly elevated triglycerides, what is the most likely diagnosis and how should it be evaluated and managed?

Hyperprolactinemia with Secondary Hypogonadism

This 27-year-old man has hyperprolactinemia (prolactin 37.5 ng/mL, normal <15) causing secondary hypogonadism, and requires immediate repeat prolactin measurement followed by pituitary MRI if persistently elevated, with endocrinology referral for probable prolactinoma management. 1

Diagnostic Interpretation

Hormonal Pattern Analysis

The laboratory findings reveal a clear pattern of secondary (hypogonadotropic) hypogonadism caused by hyperprolactinemia: 1

• Total testosterone 8.3 nmol/L (239 ng/dL) is below the diagnostic threshold of 300 ng/dL for hypogonadism 1, 2
• Free testosterone 221 pmol/L (64 pg/mL) is markedly low, well below the 2.5th percentile of 120 pg/mL for men aged 19-39 years 3
• Prolactin 37.5 ng/mL is 2.5-fold above the upper limit of normal (>15 ng/mL), meeting criteria for hyperprolactinemia 1
• FSH 0.8 IU/L is suppressed below the normal range (1.0-18.0), indicating hypothalamic-pituitary dysfunction 1
• LH 5.5 IU/L is inappropriately normal-to-low given the severely low testosterone, confirming secondary hypogonadism 1

Prolactin-to-Testosterone Ratio

The prolactin-to-testosterone ratio is 0.16 (37.5 ng/mL ÷ 239 ng/dL), which exceeds the 0.10 threshold strongly predictive of pituitary abnormalities in men with mild hyperprolactinemia and hypogonadal symptoms. 4 This ratio, combined with prolactin >25 ng/mL, achieves 90% sensitivity for detecting pituitary lesions and indicates high probability of a structural pituitary abnormality requiring imaging. 4

Mechanism of Hyperprolactinemia-Induced Hypogonadism

Elevated prolactin suppresses gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus and may prevent the pituitary from responding to GnRH, resulting in low LH and FSH secretion despite profoundly low testosterone levels. 5 This explains the constellation of low testosterone, suppressed FSH, and inappropriately normal LH in this patient. 1, 5

Immediate Diagnostic Steps

Step 1: Confirm Persistent Hyperprolactinemia

Repeat prolactin measurement immediately to exclude spurious elevation, as single measurements can be artifactually elevated due to stress, recent sexual activity, or venipuncture-related factors. 1 The AUA guideline explicitly states that prolactin measurement should be repeated to ensure the initial elevation was not spurious before proceeding with further evaluation. 1

Step 2: Pituitary MRI if Prolactin Remains Elevated

If repeat prolactin confirms persistent elevation (>15 ng/mL), order pituitary MRI with gadolinium contrast to evaluate for prolactinoma or other pituitary lesions. 1 The AUA guideline states that persistently elevated prolactin levels can indicate the presence of pituitary tumors such as prolactinomas, and such patients should be referred to an endocrinologist for further evaluation. 1

Critical caveat: While the AUA guideline reserves mandatory pituitary MRI for men with total testosterone <150 ng/dL combined with low/normal LH regardless of prolactin level 1, this patient's prolactin elevation of 2.5-fold above normal and prolactin-to-testosterone ratio of 0.16 independently warrant imaging even though his testosterone is 239 ng/dL. 4

Step 3: Endocrinology Referral

Refer to endocrinology immediately for evaluation of hyperprolactinemia and management of probable prolactinoma. 1 Patients with persistently high prolactin levels of unknown etiology should undergo evaluation for endocrine disorders by a specialist. 1

Expected Pituitary Imaging Findings

Given this patient's prolactin level of 37.5 ng/mL (mild hyperprolactinemia, defined as 15.1-50.0 ng/mL), the most likely finding is a microprolactinoma (<10 mm diameter). 4 Prolactin levels correlate with tumor size: microprolactinomas typically produce prolactin levels of 25-100 ng/mL, while macroprolactinomas (≥10 mm) usually cause prolactin >200 ng/mL. 1

Treatment Algorithm

Primary Treatment: Dopamine Agonist Therapy

Cabergoline is first-line medical therapy for prolactinoma, as it normalizes prolactin levels, shrinks tumor size, and restores gonadal function in the majority of patients. 6, 5 When prolactin is lowered with bromocriptine (a dopamine agonist similar to cabergoline), testosterone and gonadotropin levels rise substantially within 3-8 weeks, with testosterone reaching maximum levels by 15 weeks. 5

Cabergoline dosing: Typical starting dose is 0.25-0.5 mg twice weekly, titrated based on prolactin response. 6

Monitoring requirements for cabergoline: 6

• Baseline echocardiogram before initiating therapy to assess for valvular disease (contraindication to cabergoline) 6
• Repeat echocardiogram every 6-12 months during treatment, as cardiac valvulopathy has been reported with cabergoline, particularly at high doses 6
• Discontinue cabergoline if echocardiogram reveals new valvular regurgitation, restriction, or leaflet thickening 6
• Monitor for extracardiac fibrotic reactions (pleural, pericardial, retroperitoneal fibrosis) with chest X-ray, ESR, and serum creatinine as clinically indicated 6

Testosterone Replacement Therapy: Absolutely Contraindicated

Do not initiate testosterone replacement therapy in this patient. 1, 7 Exogenous testosterone is absolutely contraindicated in men with secondary hypogonadism who may desire fertility preservation, as it suppresses spermatogenesis and causes prolonged, potentially irreversible azoospermia. 1, 7 At age 27, fertility preservation is a critical consideration even if the patient has not explicitly stated fertility desires. 1

The correct approach is to treat the underlying cause (hyperprolactinemia) rather than replace testosterone. 1, 5 Lowering prolactin with dopamine agonist therapy will restore the hypothalamic-pituitary-gonadal axis, allowing endogenous testosterone production and spermatogenesis to recover. 5

Alternative if Dopamine Agonist Fails or is Contraindicated

If dopamine agonist therapy fails to normalize prolactin or is contraindicated due to cardiac valvular disease, gonadotropin therapy (recombinant hCG plus FSH) is the appropriate treatment to restore both testosterone levels and fertility potential in secondary hypogonadism. 1, 7 This directly stimulates the testes, bypassing the suppressed hypothalamic-pituitary axis. 1, 7

Expected Treatment Outcomes

Timeline for Hormonal Recovery

Based on the case report of bromocriptine treatment in hyperprolactinemic hypogonadism: 5

• Prolactin normalization: Within 3 weeks of dopamine agonist initiation 5
• LH/FSH rise: Substantial increase by 3 weeks, reaching supraphysiologic levels by 8 weeks, normalizing by 15 weeks 5
• Testosterone rise: Begins after 3 weeks, reaches maximum by 15 weeks 5
• Symptom improvement: Libido and erectile function typically improve within 3-6 months of testosterone normalization 7

Monitoring During Treatment

Repeat laboratory testing 8-12 weeks after initiating dopamine agonist: 1, 7

• Prolactin level (target: <15 ng/mL) 1
• Morning total testosterone (target: >300 ng/dL) 1, 7
• LH and FSH (expect normalization as prolactin falls) 1, 5

Repeat pituitary MRI 6-12 months after treatment initiation to assess tumor size response to dopamine agonist therapy. 6

Critical Pitfalls to Avoid

Do Not Diagnose "Testosterone Deficiency" Without Addressing Hyperprolactinemia

The primary diagnosis is hyperprolactinemia causing secondary hypogonadism, not isolated testosterone deficiency. 1 Treating with testosterone replacement would mask the underlying pituitary pathology, suppress fertility, and fail to address the root cause. 1, 7

Do Not Skip Repeat Prolactin Measurement

A single elevated prolactin can be spurious due to stress, recent sexual activity, or venipuncture. 1 The AUA guideline explicitly requires repeat measurement to confirm persistent elevation before proceeding with MRI and endocrinology referral. 1

Do Not Delay Pituitary Imaging

With prolactin 2.5-fold elevated and prolactin-to-testosterone ratio of 0.16, this patient has 90% probability of a pituitary abnormality on MRI. 4 Delaying imaging risks missing a growing prolactinoma that could cause visual field defects from optic chiasm compression or hypopituitarism. 1

Do Not Assume Age-Related Decline in a 27-Year-Old

Testosterone deficiency at age 27 is never physiologic and always warrants investigation for secondary causes. 7 This patient's suppressed FSH and elevated prolactin immediately identify the etiology as hyperprolactinemia-induced secondary hypogonadism. 1

Additional Laboratory Findings

Other Hormonal Parameters

• Estradiol 74 pmol/L (<160) is normal and does not require intervention 1
• SHBG 16 nmol/L (6-65) is low-normal, which actually increases free testosterone fraction; the low free testosterone despite low SHBG confirms true severe hypogonadism 7, 8
• PSA 0.3 ng/mL (<2.6) is normal for age and does not affect management 1

Metabolic Parameters

• Triglycerides 2.07 mmol/L (goal <1.70) are mildly elevated and may improve with testosterone normalization after prolactin treatment, as testosterone therapy improves triglyceride levels in hypogonadal men 7
• Address cardiovascular risk factors (elevated triglycerides) with lifestyle modification while treating hyperprolactinemia 7

Summary of Management Plan

1. Repeat prolactin measurement immediately to confirm persistent elevation 1
2. Order pituitary MRI with contrast if prolactin remains >15 ng/mL 1, 4
3. Refer to endocrinology for prolactinoma management 1
4. Initiate cabergoline (after baseline echocardiogram) to normalize prolactin and restore testosterone 6, 5
5. Recheck prolactin, testosterone, LH, FSH at 8-12 weeks to assess treatment response 1, 7, 5
6. Repeat pituitary MRI at 6-12 months to assess tumor response 6
7. Do not prescribe testosterone replacement therapy due to fertility concerns and presence of treatable secondary cause 1, 7