Purpose: Acute liver failure (ALF) is characterized by abrupt onset of jaundice, coagulopathy and hepatic encephalopathy in the absence of preexisting liver disease. Medullary thyroid cancer (MTC) is a rare calcitoninsecreting tumor. ALF from metastasis is uncommon and even rarer when it occurs secondary to metastatic MTC. We found no published reports of ALF from metastatic MTC after conducting a systematic search of Medline and Embase. Results: A 59 y.o. male without significant medical history or medication use presented with neck lymphadenopathy. He had no history of alcohol use, smoking or head and neck radiation. CT scan of the neck showed a heterogeneous mass in the right thyroid lobe. Excisional biopsy revealed MTC. Calcitonin was elevated at 4,402 pg/ml, CEA was 9,483 ng/ml. RET gene mutation was negative. In screening for metastasis, abdominal CT showed multiple hypodense liver lesions; the largest was in segment 8 (5.3 x 4.4 cm). Staging PET showed foci of intense FDG uptake in the neck and liver (see Figure), the largest of which corresponded with the same area noted on the CT scan. He underwent tumor debulking and was found to have adjacent muscle and adipose tissue involvement with positive cervical lymph nodes. Prior to planned chemotherapy, he presented with jaundice, fever and encephalopathy. Hematocrit was 38.8%, platelets 91,000/cumm, WBC 22,500/cumm, albumin 2.8 g/dl, direct bilirubin 6 mg/dl, AST 310 u/l, ALT 186 u/l, alkaline phosphatase 335 u/l, INR 2.8, plasma ammonia 128 μmol/L and LDH 920 u/l. Tests for Hepatitis A, B and C, hepatotoxins, autoimmune markers and blood cultures were negative. Ultrasound with doppler noted increased liver heterogeneity, consistent with progression of metastases, but no portal or hepatic vascular occlusion or biliary obstruction. The patient's mental status continued to deteriorate and he expired after progression to hepatic coma, shock and multiorgan failure. Conclusion: Our case suggests metastatic MTC as a rare cause of ALF. The diagnosis of ALF from MTC infiltration is supported by extensive hepatic lesions, persistently elevated calcitonin levels and absence of viral, metabolic or toxicologic etiologies.Figure