Can hypothyroidism cause elevated Carbohydrate Antigen 19 (CA-19) levels?

Can Hypothyroidism Cause Elevated CA-19-9?

No, hypothyroidism does not cause elevated CA-19-9 levels based on the available evidence, though it can elevate other tumor markers like CEA and CA-125.

Evidence from Thyroid Disease Studies

The most direct evidence comes from a study specifically examining CA-19-9 in Hashimoto's thyroiditis (autoimmune hypothyroidism):

• In 71 patients with Hashimoto's thyroiditis, mean CA-19-9 levels were normal (12.5 ± 10.4 U/mL, range 2.5-55), with no significant difference compared to healthy controls (10.3 ± 8 U/mL). 1
• There was no relationship between CA-19-9 levels and thyroid status (hypothyroid, hyperthyroid, or euthyroid states). 1
• This contradicts earlier case reports suggesting possible CA-19-9 elevation in Hashimoto's thyroiditis. 1

Contrast with Other Tumor Markers in Hypothyroidism

While CA-19-9 remains normal, hypothyroidism can cause marked elevation of other tumor markers:

• CEA (carcinoembryonic antigen) can be markedly elevated in severe hypothyroidism and decreases with levothyroxine replacement therapy alone. 2, 3
• CA-125 can also be significantly elevated in hypothyroidism, particularly when associated with pleural/pericardial effusions and ascites, and normalizes with thyroid hormone replacement. 3

Clinical Pitfalls to Avoid

When encountering elevated CA-19-9, do not attribute it to hypothyroidism—instead, pursue the standard differential diagnosis:

Benign Causes of CA-19-9 Elevation:

• Biliary obstruction (10-60% false-positive rate)—check total bilirubin immediately and obtain liver function tests. 4
• Inflammatory hepatobiliary conditions (cholangitis, choledocholithiasis). 4
• Pancreatitis (acute, chronic, or autoimmune). 4
• Severe hepatic injury from any cause. 5, 4
• Inflammatory bowel disease. 5, 4

Malignant Causes:

• Pancreatic adenocarcinoma (elevated in up to 85% of cases). 4
• Cholangiocarcinoma (elevated in up to 85% of cases). 5, 4
• Other gastrointestinal malignancies (colorectal, hepatocellular, gastric). 4

Diagnostic Algorithm for Elevated CA-19-9

When CA-19-9 is elevated, follow this approach regardless of thyroid status:

1. Check total bilirubin and liver function tests first—hyperbilirubinemia causes false elevation and must be addressed before interpretation. 4, 6

2. Obtain abdominal ultrasound as first-line imaging to assess for biliary obstruction. 5, 4

3. If biliary obstruction is present, perform biliary decompression and recheck CA-19-9 afterward—persistent elevation strongly suggests malignancy. 5, 4

4. For suspected cholangiocarcinoma or persistent elevation, obtain MRI with MRCP (optimal investigation providing biliary anatomy and tumor extent). 5, 4, 6

5. Consider abdominopelvic CT (94.1% sensitivity for detecting malignancies causing elevated CA-19-9). 4, 6

6. Never rely on CA-19-9 alone for diagnosis—always confirm with imaging and/or biopsy. 4, 7

Important Caveats

• Approximately 5-10% of the population is Lewis antigen-negative and cannot produce CA-19-9, making testing ineffective in these individuals. 4, 7
• CA-19-9 is not tumor-specific and should never be used as a screening test in asymptomatic individuals. 4, 7
• Values >100 U/mL have 75% sensitivity and 80% specificity for cholangiocarcinoma in PSC patients, but this threshold is not absolute. 5, 4