S5875 Unexpected Dopaminergic Surge: Elevated Urinary Dopamine Associated with Resmetirom Therapy—A Case Report

Introduction: Resmetirom (Rezdiffra) is used to treat non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and potentially cirrhosis. Despite its clinical benefits, Resmetirom is associated with a spectrum of gastrointestinal side effects, including diarrhea, abdominal pain and vomiting, are significant but increase in urinary dopamine is yet underrecognized. Case Description/Methods: A 50-year-old man presented to the emergency room on June 20, 2024, with epigastric pain. Computed tomography (CT) scan revealed cirrhosis, a 2.1 cm benign left adrenal lipid-rich adenoma, and diffuse hepatic steatosis with lobulated hepatic contours. Lab results showed normal liver function tests (LFTs) and a platelet count of 177. His medical history included fatty liver, type 2 diabetes, hypertension, and benign left adrenal adenoma. In August 2024, liver fibrosis score was F1-F2 (0.34), and chronic liver workup was negative for common liver diseases. Further assessments, including Fib-4 (1.22) and Ishak score (0-1), indicated early-stage liver damage. In September 2024, an ultrasound elastogram showed liver stiffness of 8.6 kPa (F2-F3). Eesophagogastroduodenoscopy and colonoscopy revealed mild chronic gastritis. Urinary dopamine before starting resmetirom in October 2024 was 370 (normal range). Blood pressure was elevated since November 2024 despite hypertension treatment. Urine dopamine levels were ordered and showed elevated levels at 578, and a follow up CT scan showed no change in the adrenal adenoma. After discontinuing resmetirom, dopamine levels normalized, leading to discontinuation of the medication. Discussion: Resmetirom works by activating thyroid hormone receptor beta (THR-β) specifically in the liver, leading to increased fatty acid oxidation, improved lipid metabolism, and reduced hepatic steatosis. Reduction of liver fat by stimulating the thyroid hormone receptor beta in the liver, resmetirom improves the clearance of triglycerides and other fats in liver cells. It also has anti-inflammatory Effects, helping reduce inflammation and fibrosis associated with liver damage, potentially slowing the progression from NAFLD to more severe conditions like NASH or cirrhosis. In this case, the patient's increased urinary dopamine is seen due to resmetirom contributing to increased blood pressure and stress. Management involves discontinuation of the offending agent.