Presentation and Outcome of Severe Graves’ Disease

Abstract Introduction: Subjects with “severe” Graves’ disease (GD) are known to have adverse outcomes. They have multisystem involvement (orbitopathy, dermopathy), more severe clinical features, large goitres and a higher relapse rate. Also, their response to thionamides is slower. There is a developing consensus that early definitive treatment improves prognosis in them. Methods: We retrospectively analysed the electronic case records and biochemistry databases of all subjects seen in our University Health Board between January 2017 and October 2019 with GD. Severe GD was defined by (1) a thyrotropin receptor antibody (TRAb) value greater than 10U/l (normal range: less than 0.9), (2) with any one of the following - (a) free thyroxine (T4) above 50pmol/l (reference range 9-19.1), (b) a combination of T4 more than 40 pmol/l with triiodothyronine (T3) above the detection range of the assay (46.1 pmol/l), (c) the presence of a large goitre, (d) active Graves’ orbitopathy (GO) or (e) dermopathy. We compared subjects with severe GD to those who did not fulfil the above criteria i.e. non-severe GD. Results: 176 GD subjects were seen during this period - 52 (29.5%) with severe and 124 (70.5%) with non-severe GD. However, 19 severe and 26 non-severe GD subjects were on active thionamide treatment at the time of analysis, and complete details were unavailable in 41 subjects. There was a significant difference in the following features between the severe and non-severe GD groups respectively (1) their median age (39 vs.52 years), (2) median TRAb levels (25.5 vs.18.5 U/l) (3) higher prevalence of GO (38.5 vs.13.3%) and active GO (15.4 vs.0%), (4) the presence of moderate/large goitre (51.3 vs.3.3%), (5) higher number failing to normalize biochemically within the first 6 months after treatment initiation (53.9 vs.39%), (6) the presence of a family history, and (8) a higher number requiring definitive treatment within 12 months of starting treatment (9.6vs.0.81%)(p=0.001-0.026 for the above). There was no difference between the two groups in gender, treatment regime i.e. dose titration regime or block and replacement regime, number biochemically normalizing within 12 months, and those who had more than 18 months of treatment and their relapse rates (55 vs. 59.1%, p=0.84). Conclusions: We have shown that those with severe GD were younger, have higher TRAb concentrations with multisystem involvement, and delayed initial normalization of thyroid hormones. A greater number of them require definitive treatment within 12 months of treatment initiation. However, the majority in both groups normalize thyroid hormones within 12 months irrespective of the treatment regime used. Early definitive treatment is required in a significantly higher percentage of subjects with severe GD and needs to be considered in them.