Endocrine Abstracts

Introduction: Graves’ disease is the commonest cause of hyperthyroidism accounting for 80% of all cases. The first line treatment for Graves’ disease in the UK is medical therapy, most frequently using a ‘dose-titration’ regimen. Currently, there is a lack of guidance to aid clinicians in carrying out optimal dose-titration of carbimazole, resulting in a risk of under- or over-treatment. Thus, we aimed to develop a carbimazole dosing-algorithm for the medical management of Graves’ disease.

Methods: A retrospective analysis of 415 patients treated with medical therapy for Graves’ disease at Imperial College Healthcare NHS Trust during 2009–2016 identified 324 patients for inclusion to the study. Dose of antithyroid drug prescribed, thyroid hormones levels, antibody status and relevant clinical data were collated.

Results: During medical therapy, 30% of patients were over-treated and rendered hypothyroid, occurring at a median of 101 days post-initiation. Patients with highest titres of Thyroid Peroxidase Antibody had greatest risk of over-treatment following carbimazole (70% of patients with TPOAb titre>1000 u/ml were over-treated vs 24% in those with undetectable TPOAb).

There was a significant association between the median percentage fall in thyroid hormones over a 4 week period and carbimazole dose (P=0.0003; r² 0.97), identifying a dose-response relationship for carbimazole. Neither weight-based, nor split-dosing, were of significant benefit in the dosing of carbimazole (P=0.48 and P=0.67, respectively).

The risk of relapse following withdrawal of medical therapy was highest in men, current smokers, British-Caucasian patients, in those with high initial freeT₄ levels, or high TSH receptor antibody titres.

Discussion: We have developed a dosing-algorithm for carbimazole prescription based on the dose-response relationship elicited. A scoring system (Relapse Rate Score; RRS) based on risk factors identified to confer an increased risk for persistent disease was derived. The RRS can be used to identify patients more appropriately triaged towards definitive management than medical therapy.