What is the possible diagnosis for a patient with hypergonadism (elevated testosterone levels), hypogonadotropic hypogonadism (low luteinizing hormone (LH)) and abnormal liver function?

Differential Diagnosis: High Testosterone with Low LH and Abnormal Liver Function

The most likely diagnosis is exogenous anabolic steroid use, which causes suppression of the hypothalamic-pituitary-gonadal axis resulting in low LH despite elevated testosterone, with hepatotoxicity from 17-alpha-alkylated androgens. 1, 2

Primary Diagnostic Consideration: Exogenous Androgen Use

Anabolic steroid abuse is the leading cause of this specific hormonal pattern and must be ruled out first. The combination of high testosterone, suppressed LH (hypogonadotropic pattern), and liver dysfunction is pathognomonic for exogenous androgen administration. 2, 3

Key Clinical Features:

• Testosterone or androgenic anabolic steroids suppress the hypothalamic-pituitary axis through negative feedback, causing low to undetectable LH and FSH levels despite supraphysiologic testosterone. 1
• 17-alpha-alkylated steroids (methyltestosterone, methandrostenolone) are specifically implicated in cholestatic jaundice, peliosis hepatis, and liver tumors. 4
• Abnormal liver function tests occur in approximately 50% of chronic anabolic steroid users, particularly those treated for more than one year. 4
• Patients may deny use or be unaware of the contents of supplements purchased online, making history unreliable. 3

Diagnostic Workup:

• Obtain detailed medication and supplement history, specifically asking about bodybuilding supplements, performance enhancers, or testosterone products. 2, 3
• Measure serum LH and FSH—both should be suppressed (not just low-normal) in exogenous androgen use. 1, 2
• Check liver function tests including AST, ALT, alkaline phosphatase, and bilirubin to characterize hepatotoxicity pattern. 4
• Consider liver imaging if transaminases are significantly elevated to evaluate for peliosis hepatis or hepatic adenoma. 4

Secondary Consideration: Advanced Liver Disease

In men with chronic liver disease, the expected pattern is LOW testosterone with LOW LH (hypogonadotropic hypogonadism), not high testosterone. 1 This makes primary liver disease an unlikely explanation for the described presentation.

Why This Doesn't Fit:

• Advanced liver disease causes hypogonadotropic hypogonadism with low testosterone levels, not elevated testosterone. 1
• SHBG rises in compensated cirrhosis due to estrogen stimulation, but ultimately declines with progression to decompensated disease. 1
• The pattern of high testosterone with low LH contradicts the pathophysiology of liver disease-induced hypogonadism. 1

Rare Alternative: Testosterone-Secreting Tumor

Testosterone-secreting adrenal or testicular tumors can produce high testosterone with suppressed LH, but would not typically cause liver dysfunction unless there is metastatic disease. 1

When to Consider:

• If exogenous steroid use is definitively excluded through comprehensive history and urine drug screening. 3
• Perform testicular ultrasound and adrenal CT imaging to evaluate for hormone-secreting tumors. 1
• Measure DHEA-S to help localize source (elevated in adrenal tumors, normal in testicular tumors). 1

Critical Management Algorithm

Step 1: Confirm the Hormonal Pattern

• Repeat morning testosterone, LH, and FSH on at least two separate occasions to confirm persistent suppression of gonadotropins. 1, 5
• Measure free testosterone and SHBG, as elevated SHBG from liver disease could falsely elevate total testosterone while free testosterone remains normal. 1, 6

Step 2: Investigate Exogenous Source

• Directly confront the patient about anabolic steroid use, bodybuilding supplements, or testosterone products, emphasizing medical confidentiality. 2, 3
• Review all medications including over-the-counter supplements and products purchased online. 3
• Consider urine drug screening for anabolic steroids if history is unrevealing but clinical suspicion remains high. 3

Step 3: Characterize Liver Dysfunction

• Obtain complete hepatic panel including AST, ALT, alkaline phosphatase, bilirubin, albumin, and PT/INR. 4
• Perform hepatitis serologies and screen for other causes of liver disease (alcohol use, metabolic syndrome, hemochromatosis). 1, 4
• Consider liver ultrasound or CT to evaluate for structural abnormalities including peliosis hepatis or hepatic adenoma. 4

Step 4: Exclude Tumor if Steroid Use Denied

• Obtain testicular ultrasound to evaluate for Leydig cell tumor or other testosterone-secreting testicular masses. 1
• Perform adrenal CT imaging if DHEA-S is elevated or clinical features suggest adrenal pathology. 1

Common Pitfalls to Avoid

Do not assume the patient will voluntarily disclose anabolic steroid use—direct, non-judgmental questioning is essential. 3 Many patients obtain these substances through unregulated internet sources and may not recognize them as "steroids." 3

Do not attribute liver dysfunction solely to other causes (alcohol, fatty liver) without investigating the hormonal pattern. 4 The combination of findings should trigger specific inquiry about exogenous androgens.

Do not initiate testosterone replacement therapy in this setting. 1 If the patient is using exogenous steroids, additional testosterone will worsen suppression and hepatotoxicity. If a tumor is present, exogenous testosterone could mask the diagnosis. 1

Recognize that hypogonadotropic hypogonadism with high testosterone is NOT consistent with primary liver disease pathophysiology. 1 Liver disease causes low testosterone, not high testosterone, making exogenous administration the most parsimonious explanation when both are present.