What are the differential diagnoses for a male patient on testosterone (hormone replacement therapy) therapy presenting with left upper quadrant pain?

Differential Diagnoses for Left Upper Quadrant Pain in a Male Patient on Testosterone Therapy

The differential diagnosis for left upper quadrant pain in a male patient on testosterone therapy should prioritize splenic pathology (particularly splenic infarction), gastric/pancreatic disease, renal pathology, and atypical appendicitis from malrotation, while recognizing that testosterone-induced polycythemia may predispose to thromboembolic complications including splenic infarction. 1, 2

Primary Diagnostic Considerations

Splenic Pathology

• Splenic infarction is a critical diagnosis to consider, presenting with left upper quadrant or epigastric pain in 84% of cases, though associated symptoms like leukocytosis occur inconsistently (only ~25% of cases) 3
• Testosterone therapy can cause secondary polycythemia through erythrocytosis, which predisposes to thromboembolic events including splenic infarction 2, 4
• Cardiogenic emboli from atrial fibrillation account for 62.5% of splenic infarctions, but 28% occur in previously healthy patients with no recognized predisposing morbidity 3
• Clinical presentation includes left upper quadrant or epigastric pain (84%), with chest X-ray showing left supra-diaphragmatic findings in only 22% of cases 3
• Laboratory findings may show leukocytosis (14,700 with left shift) and markedly elevated LDH (945 IU), though these are inconsistent 5, 3

Pancreatic Disease

• Acute pancreatitis should be suspected when left upper quadrant pain is accompanied by vomiting, confirmed by serum amylase >4× normal or lipase >2× upper limit of normal 1
• Post-procedural pancreatitis or postembolization syndrome can present with nausea, vomiting, upper quadrant pain, and fever if recent procedures were performed 1

Gastric and Intestinal Pathology

• Splenic flexure diverticulitis or colitis extending to the left upper quadrant can mimic other causes and requires CT evaluation for diagnosis 1
• Atypical appendicitis from intestinal malrotation is a rare but critical diagnosis, as the appendix may be located in the left upper quadrant, presenting with anorexia, left upper quadrant pain, and involuntary guarding 6, 1
• Most malrotation cases remain asymptomatic until acute complications develop, requiring imaging for diagnosis 6

Renal Pathology

• Nephrolithiasis or pyelonephritis should be excluded in cases of nonspecific pain, particularly when fever is absent 1
• Renal pathology can be identified on CT despite overlying bowel gas and rib shadowing that limit ultrasound utility 1

Testosterone-Specific Considerations

Polycythemia and Thrombotic Risk

• Testosterone replacement therapy causes erythrocytosis, occurring in 2.8% with 5 mg/day patches, 11.3% with 50 mg/day gel, and 17.9% with 100 mg/day gel 4
• Unphysiologically high testosterone levels represent a rare cause of secondary polycythemia that should be considered early with appropriate medical history 2
• Hematocrit should be monitored in men receiving testosterone therapy, with dosage reduction, withholding testosterone, therapeutic phlebotomy, or blood donation instituted if erythrocytosis develops 4

Hepatic Effects

• Testosterone replacement may be associated with transient elevations in liver enzymes that are usually self-limited, though intramuscular and transdermal preparations do not appear associated with hepatotoxicity 4

Diagnostic Imaging Strategy

CT as First-Line Imaging

• CT abdomen and pelvis with IV contrast is the preferred initial imaging modality, rated 8/9 (usually appropriate) by the American College of Radiology, providing comprehensive assessment with excellent diagnostic accuracy 1
• CT alters diagnosis in nearly half of cases and identifies alternative diagnoses that alter management in 49% of patients with nonlocalized abdominal pain 1
• CT detects splenic pathology, pancreatic disease, gastric abnormalities, vascular conditions, and unexpected findings including malrotation with atypical appendicitis 1
• For splenic infarction specifically, CT evaluation is diagnostic with high accuracy 3

Limited Role of Other Imaging

• Plain radiography has very limited diagnostic value for left upper quadrant pain and is not recommended 1
• Ultrasound has limited utility due to overlying bowel gas and rib shadowing, though it may identify splenic or renal pathology 1

Critical Clinical Pitfalls

Recognition of Atypical Presentations

• Do not dismiss left upper quadrant pain as benign without imaging when clinical suspicion exists, as atypical presentations may result in diagnostic and management delay, increasing morbidity and mortality 1, 6
• Testosterone-induced polycythemia presenting with abdominal pain requires early consideration with appropriate medical history 2

Laboratory Limitations

• Do not rely on consistent laboratory findings to rule out splenic infarction, as leukocytosis and elevated LDH occur inconsistently (~25% each) 3
• Physical examination showing plethora in a patient on testosterone therapy should prompt evaluation for polyglobulia 2

Monitoring Requirements

• Hematocrit or hemoglobin levels should be monitored at baseline and during testosterone therapy, with follow-up visits at 1-2 months initially, then 3-6 month intervals 4
• PSA and digital rectal examination should be performed at baseline, though these are unrelated to left upper quadrant pain evaluation 4