Thiamazole

Abstract

Hepatotoxicity in the form of cholestatic and toxic hepatitis: 5 case reports In a study conducted in Turkey between June 2019 and September 2019, 5 patients (2 men and 3 women) aged 25–44 years were described, who developed hepatotoxicity manifesting as toxic hepatitis or cholestatic hepatitis during treatment with thiamazole for Grave’s disease. One of the 5 patients additionally developed antithyroid drug-related eruption during treatment with thiamazole for Grave’s disease [routes not stated]. Case 1: A 34-year-old woman diagnosed with Grave’s disease, and she had been receiving treatment with thiamazole [methimazole] since May 2019. She was hospitalised due to hepatotoxicity manifesting as toxic hepatitis induced by thiamazole. It was reported that from the last 3 months, she had been receiving daily 10mg of thiamazole and 40mg of propranolol. In the third month of thiamazole treatment, she complained about nausea, vomiting and diarrhoea, and her laboratory results indicated toxic hepatitis. Eventually, her thiamazole therapy was discontinued, and she was initiated on cholestyramine and methylprednisolone. Thereby, due to her enlarged thyroid gland, therapeutic plasma exchange was planned for euthyroidism before surgery. After 2 consecutive therapeutic plasma exchange therapy, her thyroid function level decreased. After that, she underwent a total thyroidectomy without any complications. After 40 days from thiamazole withdrawal, her liver function tests returned to normal range. Her hypothyroidism was achieved after the surgery, and she was started levothyroxine before discharge. Case 2: A 35-year-old man was presented to the hospital with a widespread rash after the initiation of thiamazole treatment for Grave’s disease in May 2019. He had been receiving daily 10mg of thiamazole and 40mg of propranolol for the last 1 month. From the last 2 days, he developed a papulopustular millimetric itchy rash on arms, legs, chest, back, and bilateral plantar exfoliative rash. Thereby, he underwent a dermatology consultation which revealed an antithyroid drug-related eruption. Therefore, he underwent hepatic function tests, which had increased two-three-fold. Thereby, he was diagnosed with thiamazole induced hepatotoxicity manifesting as toxic hepatitis. His thiamazole treatment was discontinued. The therapy with propranolol was continued, and methylprednisolone and cholestyramine were added. He underwent 3 consecutive therapeutic plasma exchange without any complications, and her thyroid function level decreased. After that, he underwent a total thyroidectomy. After 40 days from thiamazole withdrawal, his liver function tests returned to the normal range. His hypothyroidism was achieved after the surgery, and he was started levothyroxine-sodium treatment. Case 3: A 44-year-old man diagnosed with Grave’s disease in January 2019, and he was initiated on treatment with propylthiouracil. However, he discontinued the treatment by his own. Through a biochemical examination and thyroid scintigraphy, he was detected to have hyperthyroidism. In May 2019, he was initiated treatment with 15mg of thiamazole and 40mg of propranolol. However, after 1 month of thiamazole therapy, he developed hepatotoxicity manifesting as toxic hepatitis, and his liver function tests were increased a 3-fold. Thereby, his thiamazole treatment was discontinued. He was started therapy with methylprednisolone and underwent therapeutic plasma exchange without any complications. After that, his thyroid function level was decreased. He underwent surgery after 18 h of the last session of therapeutic plasma exchange. After the surgery, he developed transient hypocalcaemia. After 30 days from thiamazole withdrawal, his liver function tests returned to the normal range. His hypothyroidism was achieved after the surgery, and he was started levothyroxine-sodium treatment. Case 4: A 25-year-old woman was diagnosed with Grave’s disease, and she was initiated on treatment with thiamazole from the last 2 weeks. She was referred to the hospital in July 2019 due to impaired liver function tests, and she also developed nausea, vomiting and abdominal pain. She reported that in 2016 she was first diagnosed with Graves’ disease, and she had started receiving 30mg of thiamazole. However, she discontinued the treatment by her own as her euthyroid status was achieved. During her recent presentation, a physical examination was performed, which showed mild icteric sclera and significant tenderness in the right upper quadrant of the abdomen. After the first month of thiamazole treatment, her liver function tests were noted to be increased 3-fold. Hence, an abdominal USG was performed, which showed hydropic gallbladder, but cholelithiasis was not found. Eventually, she was suspected to have cholestatic hepatitis (hepatotoxicity). Hence, her thiamazole treatment was discontinued, and she started receiving methylprednisolone, propranolol and cholestyramine. She underwent 3-sessions of therapeutic plasma exchange without any complications due to euthyroidism, and she underwent a surgery. After that, her thyroid function level decreased. However, she experienced perioperative bleeding. Her aPTT and PT levels were prolonged to 44.3 and 20.5s. After 20 days from thiamazole withdrawal, her liver function tests returned to the normal range. Hypothyroidism was achieved after the surgery, and he was started levothyroxine-sodium treatment. Case 5: A 38-year-old woman had been diagnosed with Grave’s disease in February 2019, and she had been receiving treatment with thiamazole. Three months after the initiation of thiamazole therapy, she was referred to the hospital due to cholestatic hepatitis (hepatotoxicity). Thereby, her thiamazole treatment was discontinued, and she was initiated on treatment with methylprednisolone, propranolol and cholestyramine. She was also diagnosed with inactive Grave’s ophthalmopathy. Therefore, she underwent 5-sessions of therapeutic plasma exchange, and her thyroid function level was decreased. She underwent total thyroidectomy after 2h of the last session of therapeutic plasma exchange. During the surgery, she developed bleeding. Her activated partial thromboplastin time and prothrombin time were prolonged to 37.2 and 19.9s. Subsequently, a blood transfusion was performed. However, on day 3 of the surgery, she developed back pain, and shortness of breath, and pulmonary embolism was detected through a pulmonary CT angiogram. On the fifth day after surgery, she developed neck pain, and her CRP level was increased, and she started treatment with ceftriaxone. She also developed transient hypoparathyroidism, and for 2 weeks, she received treatment with calcium and active vitamin-D treatment. After 60 days of thiamazole withdrawal, her liver function tests returned to the normal range. Post-surgery, she was initiated on therapy with levothyroxine-sodium. After 3 months of the surgery, she was diagnosed with right lymphadenopathy, and reoperation was planned.