What is the cause of right hypochondriac tenderness with normal ultrasound, normal Creatine Phosphokinase (CPK), and normal Liver Function Tests (LFT)?

Right Hypochondriac Tenderness with Normal Investigations

The most likely causes in this clinical scenario are musculoskeletal pain, early biliary pathology not yet detectable on ultrasound, or functional disorders, though further imaging with MRCP or CT may be warranted if symptoms persist or worsen. 1, 2

Initial Diagnostic Considerations

The combination of right upper quadrant tenderness with normal ultrasound, normal CPK, and normal liver function tests significantly narrows the differential diagnosis:

• Normal ultrasound has 96% accuracy for detecting gallstones but can miss early acute cholecystitis, small common bile duct stones (sensitivity only 22.5-75% for CBD stones), and other subtle biliary pathology 2, 1
• Normal CPK effectively excludes rhabdomyolysis and significant muscle injury, which would present with markedly elevated CPK levels 3, 4
• Normal LFTs make hepatobiliary disease less likely but do not completely exclude it, as early biliary obstruction or cholecystitis can present before enzyme elevation 1

Most Probable Diagnoses

Musculoskeletal Pain

• Abdominal wall pain or costochondritis is a common cause of localized tenderness with completely normal investigations 2
• This diagnosis should be strongly considered when all objective testing is normal

Early or Atypical Biliary Disease

• Acute cholecystitis can present with normal initial ultrasound in up to 8-24% of cases, particularly early in the disease course 1
• Atypical pain or no pain occurs in 12% of elderly patients with acute cholecystitis, though typical right hypochondriac pain occurs in 72-93% of cases 1
• Anicteric cholestasis from vascular malformations can cause right upper quadrant discomfort with normal standard investigations 1

Right-Sided Colonic Pathology

• Right-sided colonic diverticulitis can present with right upper quadrant or right lower quadrant pain and may be missed on standard ultrasound if not specifically evaluated 5
• Ultrasound has 91.3% sensitivity for right-sided diverticulitis when the colon is carefully examined 5

Functional Disorders

• Biliary dyskinesia or sphincter of Oddi dysfunction can cause typical biliary-type pain with completely normal standard investigations 1

Recommended Diagnostic Approach

When to Pursue Additional Imaging

If clinical suspicion remains high despite normal initial testing, proceed with advanced imaging rather than observation alone:

• MRCP is the preferred second-line test with 85-100% sensitivity for cholelithiasis/choledocholithiasis and 90% specificity, superior to CT for biliary sources 2, 1
• CT with IV contrast is appropriate if complications like abscess, perforation, or non-biliary pathology are suspected 6, 2
• Hepatobiliary scintigraphy (HIDA scan) is the gold standard when ultrasound is inconclusive for acute cholecystitis 2

Clinical Red Flags Requiring Further Investigation

Pursue additional testing if any of the following are present:

• Fever, which suggests infectious or inflammatory process requiring urgent evaluation 6, 1
• Progressive or worsening pain despite conservative management 1
• Development of jaundice or abnormal LFTs on repeat testing 1
• History of recent seafood consumption with myalgias (consider Haff disease with rhabdomyolysis) 3

Important Clinical Pitfalls

Technical Limitations of Initial Ultrasound

• Obesity, bowel gas, and abdominal tenderness can limit ultrasound accuracy and may necessitate alternative imaging 2
• Operator experience significantly affects interpretation, particularly for subtle findings 2
• Serial ultrasound examinations may be needed as failure of abnormalities to progress on follow-up scans has excellent negative predictive value 1

Conditions That Can Be Missed

• Small CBD stones have low ultrasound sensitivity (22.5-75%) and may require MRCP for detection 2, 1
• Early acalculous cholecystitis may not show classic ultrasound findings initially 1
• Non-alcoholic fatty liver disease requires >33% lipid content to be detected on ultrasound, with sensitivity dropping to 53-65% for mild steatosis 2

When Conservative Management is Appropriate

If all investigations remain normal and red flags are absent:

• Musculoskeletal causes can be managed conservatively with analgesics and observation
• Functional disorders may require specialized testing (e.g., cholecystokinin-stimulated cholescintigraphy for biliary dyskinesia) if symptoms persist 1
• Close follow-up is essential as some conditions evolve over time and may require repeat evaluation 1