Can Hypothyroidism Cause Slightly Elevated Bilirubin?
Yes, hypothyroidism can cause mild elevation of bilirubin, primarily affecting total and conjugated bilirubin levels, though this is not a typical or prominent feature of thyroid dysfunction. 1
Mechanism and Pattern of Elevation
Hypothyroidism alters liver function tests including bilirubin metabolism, with studies demonstrating significant increases in total bilirubin concentrations in hypothyroid patients compared to euthyroid controls. 1
The elevation is predominantly conjugated (direct) bilirubin due to cholestatic effects, as hypothyroidism causes a 50% decrease in bile flow and reduced maximal biliary excretion of bilirubin. 2
Hypothyroidism increases the ratio of bilirubin diconjugates to monoconjugates in bile, liver, and plasma, reflecting increased hepatic conjugation activity and prolonged retention of bile pigments in hepatocytes. 2
The cholestatic condition also decreases biliary output of unconjugated bilirubin, which may represent an indirect effect related to decreased output of bilirubin monoconjugates with impaired hydrolysis. 2
Clinical Significance and Associated Findings
Bilirubin elevation in hypothyroidism is typically accompanied by other liver function abnormalities, including decreased albumin levels (3.9 vs. 4.3 g/dL in euthyroid patients) and elevated liver enzyme activities. 3, 1
The correlation between thyroid hormones and liver enzymes is negative in hypothyroid subjects (opposite to hyperthyroid patients), meaning as thyroid hormone levels decrease, bilirubin and liver enzymes increase. 1
Younger patients with liver disease and hypothyroidism show more pronounced TSH elevation, with median age of 5 years versus 9 years in those without TSH elevation. 3
Important Clinical Caveats
Liver function test interpretation in thyroid dysfunction requires caution, as both hyperthyroidism and hypothyroidism can alter these parameters independently of primary liver disease. 1
The bilirubin elevation is usually mild and resolves with thyroid hormone replacement, distinguishing it from primary hepatobiliary pathology that requires different management. 2
When evaluating elevated bilirubin, thyroid function should be assessed, particularly if other causes of conjugated hyperbilirubinemia (viral hepatitis, autoimmune hepatitis, biliary obstruction, drug-induced liver injury) have been excluded. 4, 5
Ultrasound abdomen remains the first-line imaging (98% positive predictive value for liver parenchymal disease) to exclude structural hepatobiliary pathology when bilirubin is elevated, regardless of thyroid status. 4, 5
Differential Diagnosis Considerations
Most isolated elevated bilirubin is due to Gilbert's syndrome (impaired conjugation via reduced glucuronyltransferase activity), which causes unconjugated hyperbilirubinemia and should be distinguished from hypothyroid-related conjugated elevation. 4
If conjugated bilirubin represents >35% of total bilirubin, this confirms true conjugated hyperbilirubinemia requiring evaluation for intrahepatic or posthepatic causes, including thyroid dysfunction. 5
Thyroid-stimulating hormone should be measured at diagnosis when clinically stable or after glycemic control is established, as thyroid function tests can be misleading during acute illness (euthyroid sick syndrome). 4