Thyroid Storm Presenting With Profound Cholestatic Liver Injury: A Rare Diagnostic Dilemma

Abstract

Introduction: Thyrotoxicosis from Graves disease can cause multi-organ dysfunction including abnormal liver function tests. Severe cholestatic liver injury directly caused by thyroid storm is rare, and can pose a diagnostic dilemma with etiologies such as congestive heart failure, drug-induced liver injury, concurrent primary biliary cirrhosis (PBC), or autoimmune hepatitis (AIH) being more common. We report an unusual case of thyroid storm-induced profound cholestatic liver injury mimicking PBC and AIH overlap syndrome. A 35-year-old female with an unremarkable past medical history presented to a local hospital with a 2-day history of jaundice and pruritus. Physical examination was significant for thyromegaly and right upper quadrant abdominal tenderness. Liver function tests revealed aspartate aminotransferase (AST) of 1935 unit/L, alanine aminotransferase (ALT) of 982 unit/L, alkaline phosphatase of 484 unit/L, total bilirubin (TB) of 21.6 mg/dL, direct bilirubin (DB) of 16.3 mg/dL, INR of 1.8, and a high gammaglobulin (IgG) level. A liver biopsy showing moderate mixed portal and lobular inflammation, bile duct injury, and focal ductular reaction was interpreted as PBC and AIH overlap syndrome. She was discharged after clinical improvement on prednisone. She presented to our hospital 5 days later with new onset tachycardia of 120 beats per minute, thyroid bruit, diffuse abdominal tenderness, and resting tremor. Laboratory data showed improved but abnormal AST, ALT, and INR, and increased TB of 31.1 mg/dL and DB >20.0 mg/dL. Viral hepatitis serologies, antimitochondrial antibody, anti-liver-kidney microsomal antibody, antinuclear antibody, and anti-smooth muscle antibody were negative. IgG level normalized. Her thyroid stimulating hormone (TSH) was <0.01 mcIU/mL and free thyroxine (FT4) was 5.9 ng/dL. TSH receptor antibodies and thyroid stimulating immunoglobulin were positive, suggestive of thyroid storm secondary to Graves disease. A CT scan of the abdomen and transthoracic echocardiogram were grossly normal. Potassium iodide was promptly started. On hospital day 8, she underwent a thyroidectomy given limited medical options. Three weeks after FT4 normalized, her liver function tests also returned to normal. This case demonstrates that in the absence of autoantibodies, hepatotoxic medication, and congestive heart failure, thyrotoxicosis can be a direct cause of severe cholestatic liver injury. It can also produce inflammatory changes and bile duct injury typical of PBC or AIH overlap syndrome. Special attention should be paid to thyroid abnormalities, since early recognition is of paramount importance and appropriate treatment can reverse the hepatic injury, as seen in our case.