Endocrine Abstracts

Introduction: Carbimazole hepatotoxicity occurs in ~0.1–0.2% of patients. A 2024 systematic review of 271 antithyroid-drug–induced liver injury (DILI) cases found carbimazole/methimazole accounted for 55.7%. Among these, 67.4% had a cholestatic pattern, 90.7% achieved complete resolution after drug withdrawal, and mortality was 5.6%.

Case 1: A 63-year-old woman with Graves’ disease on carbimazole 40 mg daily presented after two months with pruritus and abnormal liver tests (ALT 218 U/l, ALP 723 U/l, GGT 711 U/l, bilirubin 21 μmol/l). Workup excluded viral, autoimmune, metabolic causes, and imaging showed normal biliary anatomy. After stopping carbimazole, liver function normalized within eight weeks. She underwent total thyroidectomy for definitive therapy.

Case 2: A 71-year-old man with multinodular goitre and intermittent T3 toxicosis began carbimazole 5 mg daily, and routine monitoring revealed elevated ALP, prompting immediate cessation. Rechallenge produced recurrent ALP 221 U/l and GGT 226 U/l (normal ALT, bilirubin), confirming causality. He subsequently received radioiodine therapy.

Discussion: These cases typify carbimazole-induced hepatotoxicity: a primarily cholestatic pattern (67.4%), median onset ~28 days (14–42 days), and an idiosyncratic mechanism—as evidenced by Case 2’s reaction to a low dose. Positive rechallenge (though successful in only ~75% of cases) strengthens causality. Both recovered fully, consistent with the 90.7% resolution rate. Early detection, whether by routine monitoring or prompt evaluation of symptoms (e.g. pruritus), is key. Compared to propylthiouracil, carbimazole carries a lower risk of severe outcomes: no reported liver transplants in carbimazole-only cases and lower mortality (5.6% vs ~14.3%). Median recovery is ~58 days post-discontinuation.

Conclusion: Clinicians should maintain vigilance for cholestatic hepatitis within 4–8 weeks of carbimazole initiation. Immediate drug discontinuation and timely transition to definitive therapy (surgery or radioiodine) yield excellent prognosis, with >90% achieving full resolution.