Serum Copper of 140 mcg/dL: Elevated and Requires Immediate Diagnostic Workup
A serum copper level of 140 mcg/dL is elevated above normal adult ranges (typically 70-130 mcg/dL) and mandates urgent evaluation to differentiate between Wilson disease with acute liver failure, cholestatic liver disease, copper toxicity, or inflammatory/malignant conditions. 1, 2
Critical First Steps
Measure serum ceruloplasmin immediately to calculate non-ceruloplasmin-bound (free) copper, as this is the key to distinguishing dangerous copper overload from benign causes. 1, 2
Calculate Free Copper Using This Formula:
- Free copper (μg/dL) = Total serum copper (μg/dL) - [3 × ceruloplasmin (mg/dL)] 1
- Normal free copper is ≤15 μg/dL 1
- Free copper >25 μg/dL strongly suggests Wilson disease 1, 2
Diagnostic Algorithm Based on Ceruloplasmin Results
If Ceruloplasmin is Extremely Low (<5 mg/dL):
- This is strong evidence for Wilson disease and requires immediate hepatology referral 1, 2
- Obtain 24-hour urinary copper excretion (expect >100 μg/24 hours in symptomatic Wilson disease) 1, 3
- Arrange slit-lamp examination for Kayser-Fleischer rings 2
- Assess for hepatic and neuropsychiatric manifestations 1, 2
If Ceruloplasmin is Low-Normal (5-20 mg/dL):
- Calculate free copper as above 1
- If free copper is elevated (>25 μg/dL), pursue Wilson disease workup with 24-hour urinary copper 1, 2, 3
- Note: 10-20% of Wilson disease patients have normal ceruloplasmin, so normal levels do not exclude the diagnosis 1, 4
If Ceruloplasmin is Normal or High:
Your elevated total serum copper with normal/high ceruloplasmin suggests:
- Acute fulminant hepatic failure from Wilson disease (copper released from dying hepatocytes despite low ceruloplasmin) 1
- Cholestatic liver disease (primary biliary cholangitis, primary sclerosing cholangitis) 1, 2
- Inflammatory conditions (sarcoidosis can elevate copper to 30-39 μmol/L or ~190-250 μg/dL) 5
- Hematological malignancies (Hodgkin's disease, chronic lymphocytic leukemia with mean values ~180 μg/dL in active disease) 6
- Acute copper poisoning from ingestion 1, 2
Essential Concurrent Testing
Order these tests simultaneously:
- 24-hour urinary copper excretion (use copper-free containers; >40 μg/24 hours warrants investigation, >100 μg/24 hours diagnostic for symptomatic Wilson disease) 1, 3
- Comprehensive metabolic panel to assess liver function 1
- Complete blood count (copper deficiency causes cytopenias; malignancies may elevate copper) 7, 6
Critical Clinical Context
Age matters significantly:
- Wilson disease typically presents before age 40; if patient is older, consider malignancy, cholestasis, or inflammatory disease 4
- Pediatric reference ranges differ: upper limit is 153 μg/dL for children <10.3 years 8
Look for these specific clinical features:
- Neurological symptoms (tremor, dystonia, dysarthria) or psychiatric changes suggest Wilson disease 1, 7
- Jaundice, pruritus, or cholestatic pattern suggests biliary disease 1, 2
- Erythema nodosum with hilar adenopathy suggests sarcoidosis (Löfgren syndrome) 5
- Constitutional symptoms with lymphadenopathy suggest lymphoma 6
Common Pitfalls to Avoid
- Do not rely on total serum copper alone—it is often paradoxically LOW in Wilson disease due to decreased ceruloplasmin, making your elevated value particularly concerning for acute liver failure 1, 2
- Do not assume elevated copper always means Wilson disease—cholestatic liver disease, acute liver failure of any cause, and malignancies can all elevate free copper 1, 2
- Do not use spot urine samples—only complete 24-hour collections with creatinine measurement are valid 1, 3
- Do not delay workup in young patients with hepatic or neurologic symptoms—untreated Wilson disease is fatal but treatable 1, 2
Interpretation of Free Copper Results
- Free copper <10 μg/dL: Normal; elevated total copper likely due to increased ceruloplasmin from inflammation or estrogen 2, 9
- Free copper 10-25 μg/dL: Borderline; correlate with 24-hour urinary copper 1
- Free copper >25 μg/dL: Strongly suggests Wilson disease (6-fold above normal upper limit) or acute copper toxicity 1, 2, 9