Carbimazole-induced cholestatic hepatitis in Graves’ disease
A 30-year-old male patient presented to the outpatient clinic of the Endocrinology Department with chief complaints of a 6 kg weight loss over the last four months and bilateral prominent and bulging eyes. In addition he gave a history of palpitations and tremors. He also had complaints of frequent loose motions and heat intolerance. He was a known case of rheumatic heart disease with mitral stenosis under treatment with salt restriction, digoxin, and β blockers. In the last four months he was admitted thrice, with episodes of atrial fibrillation and congestive heart failure. He had no history of liver disease. He was neither a smoker nor an alcohol consumer.\nOn physical examination, he had fine tremors of both hands. His weight was 49 kg. Pulse rate was 120 beats / minute, regular, and blood pressure was 150 / 70 mmHg in the right arm supine position. Eye examination showed bilateral exophthalmos, with conjunctivitis and periorbital edema. There was diplopia on looking to both sides, indicating ophthalmoplegia amounting to stage IV NOSPECS classification. Hands were warm and moist. Thyroid was soft and diffusely enlarged with grade 3 goiter and audible bruit. The liver and spleen were not palpable. Cardiovascular system examination revealed loud first heart sound and mid-diastolic murmur, with delayed peaking at the mitral area. There was no evidence of pulmonary arterial hypertension or congestive heart failure at presentation. The other systemic examination, including per abdomen examination, was unremarkable.\nHis initial T4 was 22.4 μg / dl and TSH < 0.01 uIU / ml. He was diagnosed with Graves’ disease and started on propranolol with prednisolone for Graves’ ophthalmopathy. Carbimazole was also initiated at a dose of 30 mg per day, in two divided doses. He neither did a thyroid scan nor took I131 because of concern with iodine allergy and exacerbation of the eye manifestations. Three weeks later, FT4 was normal and TSH was < 0.03 uIU / ml. He complained of nausea and vomiting, and the accompanying attendants complained of yellowish discoloration of his eyes. Results of the liver function tests were as shown in . The laboratory findings were consistent with cholestatic jaundice. He had marked elevation of bilirubin and alkaline phosphatase. Aspartate and alanine aminotransferase were less markedly elevated. Prothrombin time was within normal limits. The test for antinuclear antibodies was negative. Abdominal ultrasound showed normal liver size and texture. The intrahepatic biliary ducts were normal and no obstruction was detected. Hepatitis serology was negative for hepatitis A, B, C, and E. As per the gastroenterologist's advice, a liver biopsy was done, which revealed cholestatic hepatitis with a paucity of bile ducts []. Carbimazole was stopped. He received radioactive iodine under the cover of prednisolone, to minimize the risk of eye sign deterioration. His liver functions normalized within two months. He developed post-radioiodine hypothyroidism and was started on thyroxine therapy. Upon re-evaluation after four and six months his liver functions were still normal.