Prediction of Relapse After Antithyroid Drugs Withdrawal: A Narrative Review

Context: Antithyroid drugs (ATD) are the first-line treatment for Graves’ disease (GD); however, relapse following treatment is approximately 30% - 40% in the first year, and 50% - 60% in the long term. Identification of risk factors that predict relapse, after discontinuing ATD, plays an important role in guiding therapeutic options. Evidence Acquisition: PubMed was used to search for studies published in English between 1995 and 2019. The following search terms were used: Graves’ disease, antithyroid drugs, relapse, recurrence, and outcome. The reference lists from review articles were also included in the search in order to find older journals. Results: Factors associated with a high recurrence rate, as reported in most studies, were divided into phenotype and genotype predictors. Phenotype factors included large goiter size, persistence of high TSH receptor antibody (TRAb), severe hyperthyroidism, smoking, younger age, male sex, and prior history of recurrence. Genotype factors included human leukocyte antigen (HLA), CD40, CTLA-4, PTPN22, Tg, and TSHR genes. In a subgroup analysis by age, genetic factors were better predictors in the younger group, while clinical signs were more useful in the older group. The reliability of using individual baseline risk factors to predict subsequent relapse is poor; however, predictive scores calculated by grouping single risk factors might help to predict future outcomes. Conclusions: Longer normalization time of TRAb, the persistence of a palpable goiter, and harboring genetic risk factors in younger patients are associated with high recurrence rate of GD. Multi-marker prediction models have been proposed and validated to improve the predictive value of relapse after ATD withdrawal.