Endocrine Abstracts

An 85-year-old lady presented to hospital with fast atrial fibrillation and had some signs of pulmonary congestion. Her admission blood tests were normal apart from a raised urea. Her liver function tests on admission were normal (AST 26 ALP 99). Thyroid function tests showed that she was thyrotoxic with fT4 42 and TSH<0.03. Her TPO antibodies were negative. She was started on carbimazole 20 mg od.

Repeat liver function tests showed that her GGT and alkaline phosphatase were increasing (AST 50, GGT 748, ALP 440 and bilirubin 74). Her hepatitis screen, liver auto-antibodies and liver ultrasound were all normal. Carbimazole was discontinued and substituted with propylthiouracil. Her liver function tests normalised and she remains euthyroid on propylthiouracil 100 mg bd.

Thionamide induced hepatotoxicity is uncommon occurring in 0.1% patients. Carbimazole and propylthiouracil induce liver dysfunction by different mechanisms. Carbimazole causes intracanalicular cholestasis and mild periportal inflammation. Slow recovery on discontinuation is usually the rule. In contrast propylthiouracil induces an allergic mediated hepatitis causing marked elevations of transaminases and submassive or massive necrosis on liver biopsy. The liver damage does not always improve despite drug discontinuation and case fatality reports of up to 25% have been reported. Occasionally liver transplantation is required.

As both drugs induce liver damage in different mechanisms it is possible to substitute thionamides with little risk of inducing further liver injury. This is exemplified in our case report where there was an excellent result with propylthiouracil with normalisation of liver function tests.