Case presentation
A 73-year-old female presented with symptomatic hyperthyroidism characterised by tachycardia, exertional dyspnoea and nocturnal pruritus. Her past medical history included osteopaenia and treatment with cholecalciferol supplements. Biochemical hyperthyroidism was confirmed with an elevated free thyroxine (fT4) of 40.8 pmol/L (10.0-19.0), elevated free triiodothyronine (fT3) of 12.6 pmol/L (3.5-6.5) and a suppressed thyroid stimulating hormone (TSH) of < 0.03 mIU/L (0.50-4.00). Thyroid peroxidase antibodies were elevated at > 1300 kIU/L and a corresponding thyroid pertechnetate study showed diffuse symmetrical uptake consistent with Graves’ disease. Oral carbimazole was commenced at 20 mg twice daily with improvement in biochemistry. However, she developed abdominal pain shortly after and investigations were consistent with diagnosis of cholestatic hepatitis given an elevated alanine aminotransferase (ALT) of 201 U/L (5-30), alkaline phosphatase (ALP) of 301 U/L (30-115) and gamma-glutamyltransferase (GGT) of 220 U/L (5-35). Her bilirubin remained normal at 13 umol/L (3-15) despite reports of dark urine. Her liver function improved with cessation of carbimazole therapy temporally supporting a diagnosis of thionamide-related hepatoxicity.
Discussion
Thionamide is a mainstay treatment of hyperthyroidism, often offered as first-line to patients who wish to defer or avoid definitive therapy. Mild elevations in serum aminotransferases are common following treatment initiation, particularly in association with propylthiouracil (1), however the occurrence of severe cholestatic hepatotoxicity is a rare phenomenon. Histopathological changes consistent with cholestasis are most common, with isolated hepatitis occurring infrequently (2). The mechanism of injury remains elusive although an immunological reaction has been proposed. A clinical diagnosis can be complicated as hyperthyroidism alone can cause liver dysfunction, although this is expected to normalise with effective treatment (3). Rapidly developing liver function derangement or persistently elevated liver enzymes despite euthyroidism should lead to clinical consideration of thionamide-related hepatoxicity and exploration of definitive therapy options.