Fatal and non-fatal adverse events of glucocorticoid therapy for Graves' orbitopathy: a questionnaire survey among members of the European Thyroid Association

Objective: The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO). Design: A questionnaire-based survey among members of the European Thyroid Association (ETA) who treat GO. Results: A response was obtained from 128 ETA members of which 115 used GC therapy for GO. The majority of respondents (83/115, 72%) used intravenous (i.v.) GC, with a relatively wide variety of therapeutic regimens. The cumulative dose of methylprednisolone ranged between 0.5 and 12 g (median 4.5 g) for i.v. GC and between 1.0 and 4.9 g (median 2.4 g) for oral GC. Adverse events were often reported during oral GCs (26/32, 81%); most side effects were non-severe, but ten respondents reported severe adverse events (hepatic, cardiovascular, and cerebrovascular complications), including two fatal cases, both receiving a total of 2.3 g prednisone. Adverse events were less common in i.v. GC (32/83 respondents, 39%), but mostly consisted of severe events, including seven fatal cases. All but one fatal event occurred in cumulative i.v. GC doses (>8 g) higher than those currently recommended. Conclusions: GCs are preferentially administered i.v. for the treatment of GO in Europe. Both oral and i.v. GC may be associated with severe adverse effects, including fatal cases, which are more frequently reported in daily or alternate day i.v. GC. IvGC therapy should be undertaken in centers with appropriate expertise. Patients should be carefully examined for risk factors before