Endocrine Abstracts

A 37-year healthy man initially presented to primary care with weight loss and palpitations and diagnosed to have thyrotoxicosis based on thyroid function tests (TFT) – TSH (< 0.05; n = 0.27-4.20μIU/l), FT4 (59.8; n = 12-22 pmol/l), and FT3 (32; n = 3.1-6.8pmol/l) . CBZ was started and 4-weeks later was seen in the Endocrine clinic where Graves’ disease was confirmed based on a goitre and positive antiTSH receptor antibody. However, we noted new abnormal liver function tests (LFT) with an elevated Alkaline-Phosphatase (ALP:296; n = 30-130 U/l) but normal Alanine transaminase (ALT), GammaGT and bilirubin. CBZ was continued pending further liver tests. 2-weeks later, his TFT’s improved, but with the progression of hepatitis with now both ALP and ALT rising to 320 U/l and 78 (n = 0-41U/l) respectively. Ultrasound liver did not show any abnormalities and liver autoimmune screen was negative. Based on temporal association with CBZ initiation; a diagnosis of Thionamide-induced hepatitis was made. CBZ was discontinued but radioiodine (RAI) treatment or surgery could not be offered since he was the principal carer of his infant. Hence, PTU was started with a warning that his hepatitis could worsen but fortunately, his hepatitis did not worsen and remains on PTU 200 mg/day with guarded monitoring of LFTs.

Discussion: Thionamide-induced hepatotoxicity has an overall incidence of < 0.5% and liver failure at 1:10000 adults. Their mechanisms are slightly different: CBZ causes dose-dependent intracannalicular cholestasis whereas PTU is associated with idiosyncratic hepatocellular damage. This case poses two interesting comments: firstly, what treatment options could be offered if PTU caused similar hepatotoxicity and both RAI and surgery were contraindicated? Secondly, it highlights the importance of checking baseline LFTs before initiation of ATDs, regular monitoring and improving awareness amongst prescribers.