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

Eur J Endocrinol. 2012 Feb;166(2):247-53. doi: 10.1530/EJE-11-0779. Epub 2011 Nov 4.

Abstract

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 treatment and monitored for side effects, which may be asymptomatic, both during and after treatment.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems / statistics & numerical data
  • Aged
  • Committee Membership
  • Data Collection
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Administration Schedule
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / mortality*
  • Endocrinology / organization & administration
  • Europe / epidemiology
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects*
  • Glucocorticoids / therapeutic use*
  • Graves Ophthalmopathy / drug therapy*
  • Graves Ophthalmopathy / epidemiology
  • Graves Ophthalmopathy / mortality
  • Humans
  • Male
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / adverse effects
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Practice Patterns, Physicians' / statistics & numerical data
  • Societies, Medical / organization & administration
  • Surveys and Questionnaires
  • Thyroid Gland
  • Young Adult

Substances

  • Glucocorticoids
  • Methylprednisolone