Endocrine Abstracts

Objectives: Although antithyroid drugs (ATD) offer potent therapeutic benefits for treating Graves’ disease (GD), they can occasionally lead to rare, potentially life-threatening adverse events (AEs), such as agranulocytosis or toxic hepatitis. As the incidence and characteristics of these life-threatening AEs in Korea have not been widely investigated, we aimed to identify the real-world features of ATD-related severe AEs.

Method: We analyzed 19,975 patients (14,444 women; mean age, 42.9 ± 14.2 years) diagnosed with GD at four tertiary referral hospitals between 2002 and 2020, with a median follow-up time of 19.9 months. GD was defined as cases with the ICD-10 code E05 and those who have received ATD at least once. Agranulocytosis was defined as absolute neutrophil count (ANC) <500/µL; toxic hepatitis was defined as aminotransferase >5 times the upper limit of normal (ULN), total bilirubin >3 times the ULN, or prothrombin time-international normalized ratio >1.5 times the ULN.

Results: Agranulocytosis occurred in 50 (0.25%) patients; moderate neutropenia (500≤ANC<1000/µl), in 222 (1.11%); and mild neutropenia (1000≤ANC <1500/µl), in 947 (4.74%). The incidence of ATD-induced toxic hepatitis was 1.80% (359/19,975). The median time to onset of agranulocytosis was 39.5 days (Interquartile range [IQR], 27-303 days), while for toxic hepatitis, it was 64 days (IQR 21-355 days). Among patients with agranulocytosis, methimazole (MMI) was used in 38 (76%) and propylthiouracil (PTU) in 13 (26%). Regarding toxic hepatitis, 270 patients (75.2%) received MMI and 33 (9.19%) received PTU. Six individuals (0.03%) required liver transplantation, and there were no cases of bone marrow transplantation. The daily mean dosage of ATD increased the risk of agranulocytosis (adjusted OR 1.01, 95% CI 1.01-1.02), and toxic hepatitis (crude OR 1.01, 95% CI 1.007-1.014). Other risk factors for toxic hepatitis included male gender, older age, PTU use, and underlying liver disease.

Conclusions: The incidence of ATD-induced agranulocytosis and toxic hepatitis is comparable to previously reported rates. However, actual life-threatening AEs seem to be rare in Korea.