What is the diagnosis and management for an adult patient with elevated lactate dehydrogenase (LDH), slightly elevated testosterone, normal cortisol and adrenocorticotropic hormone (ACTH), and elevated protein and albumin levels?

Differential Diagnosis and Management Approach

Primary Diagnostic Consideration: Germ Cell Tumor

The combination of elevated LDH, slightly elevated testosterone, and elevated protein/albumin in an adult patient most strongly suggests a germ cell tumor (GCT), particularly testicular cancer or extragonadal GCT, which requires immediate evaluation with tumor markers (AFP and β-HCG) and testicular ultrasonography. 1

Key Diagnostic Features Supporting GCT

• Elevated LDH is present in 40-60% of patients with nonseminomatous GCT and advanced seminoma, making it a critical prognostic marker 1
• Slightly elevated testosterone may reflect testicular pathology or hormonal dysregulation from a gonadal tumor 1
• Elevated total protein and albumin can occur with certain malignancies, though this is less specific 2
• Normal cortisol and ACTH effectively rule out primary adrenal pathology and Cushing's syndrome as the primary diagnosis 3, 4

Immediate Diagnostic Workup Required

Mandatory Tumor Marker Assessment

• Measure serum AFP (α-fetoprotein) and β-HCG immediately - these are essential for GCT diagnosis, with AFP elevated in 10-60% of nonseminomatous GCT depending on stage, and β-HCG elevated in 10-40% 1
• LDH should be measured as a prognostic factor in advanced disease, with elevation defined as >1.5 times the laboratory-specific upper limit of normal 1
• AFP is never elevated in pure seminoma, so elevation indicates nonseminomatous elements 1

Essential Imaging Studies

• Testicular ultrasonography with 7.5 MHz transducer is mandatory to evaluate for primary testicular tumor 1
• Chest X-ray to assess for pulmonary metastases 1
• CT scan of abdomen and pelvis to evaluate for retroperitoneal lymphadenopathy and metastatic disease 1
• Chest CT scan is indicated for nonseminomatous tumors or if chest X-ray is abnormal 1

Additional Hormonal Evaluation

• Measure LH and FSH to assess for hypogonadism or hormonal effects of testicular pathology 1
• Total testosterone measurement helps characterize the hormonal milieu 1

Alternative Diagnostic Considerations

If GCT Workup is Negative

Secondary considerations include:

• Lymphoma - can cause elevated LDH and protein abnormalities, requires peripheral blood smear, flow cytometry, and imaging 1
• Hepatocellular pathology - elevated LDH with protein/albumin changes may indicate liver disease, though normal cortisol argues against significant hepatic dysfunction 1, 5
• Macro-LDH - a benign phenomenon where LDH complexes with immunoglobulin G, causing falsely elevated levels without underlying disease 6

Distinguishing Features

• For hepatic causes: Check liver function tests (AST, ALT, bilirubin), hepatitis serologies, and consider abdominal imaging 1
• For macro-LDH: Perform polyethylene glycol precipitation test or electrophoresis to detect LDH-immunoglobulin complexes 6
• For lymphoma: Evaluate for lymphadenopathy, B symptoms (fever, night sweats, weight loss), and consider bone marrow biopsy if clinical suspicion is high 1

Critical Clinical Pitfalls to Avoid

Do Not Delay Evaluation

• In patients with life-threatening metastatic disease and unequivocally elevated AFP or β-HCG, chemotherapy must be initiated immediately without waiting for orchiectomy 1
• Testicular examination and ultrasonography cannot be deferred even if extragonadal GCT is suspected 1

Interpretation Caveats

• Mildly elevated testosterone alone is nonspecific and can occur with stress, obesity, or diurnal variation 1
• LDH elevation has many causes including hemolysis of blood sample, myocardial infarction, muscle disease, and tissue damage 1, 5
• Normal ACTH with normal cortisol definitively excludes Cushing's syndrome and primary/secondary adrenal insufficiency 3, 4, 7

Management Algorithm

If GCT is Confirmed

1. Refer immediately to urologic oncology for orchiectomy planning 1
2. Stage disease completely with tumor markers, CT imaging, and assessment of prognostic factors 1
3. For stage I disease: Consider surveillance versus adjuvant chemotherapy based on risk factors 1
4. For advanced disease: Initiate platinum-based chemotherapy according to International Germ Cell Cancer Collaborative Group (IGCCCG) risk stratification 1

If GCT is Excluded

1. Pursue alternative diagnoses systematically based on clinical presentation and additional laboratory findings 5
2. Consider hematology-oncology referral if lymphoma or other malignancy is suspected 1
3. Repeat LDH measurement and consider macro-LDH testing if persistently elevated without clear etiology 6