Reduction of the Risk of Relapse After Withdrawal of Medical Therapy for Graves' Disease

Abstract

It has been a continuing challenge to try and identify those patients with hyperthyroid Graves' disease likely to remain in remission after an antithyroid drug course or to manage the medical treatment so as to increase the chance of remission. On average, the overall relapse rate is approximately 50% and any significant reduction of this figure would be of practical as well as theoretical value. The numerous controlled prospective studies performed in many parts of the world, with varying iodine intakes, have all confirmed that the main initial features related to the subsequent risk of relapse are: young age, male gender, goiter larger than 40 mL, hypoechogenic and hypervascular gland, high level of anti-thyrotropin receptor antibody (TRAb), detected either with radioreceptor assay (TBII: >40 U/L) or the biologic stimulation assay (thyroid-stimulating antibodies [TSAb]; >300%), severity of hyperthyroidism, and possibly the presence of ophthalmopathy. Alone, each of these has a low predictive value, but together they allow evaluation of the risk of relapse, thus helping treatment choice. As to the modalities of antithyroid drug treatment, dose of the drug or addition of levothyroxine does not affect posttreatment outcome. In contrast, significantly fewer relapses occur for drug courses longer than at least 1 year. Persistence of high levels of TRAb after medical treatment is strongly predictive of relapse but this is of limited value because in most patients, TRAb levels are low or even undetectable at the end of treatment, which does not indicate for further outcome. Smoking is a significant independent risk factor for relapse. In conclusion, reduction of the risk of relapse in patients with medically treated hyperthyroid Graves' disease relies on clinical competence and appropriate management taking into account an array of factors none of which alone has definite predictive value.