Radioiodine Therapy for Graves' Disease and the Effect on Ophthalmopathy
Radioiodine Therapy for Graves' Disease and the Effect on Ophthalmopathy
Background: An association between radioiodine therapy (RAI) for Graves' disease (GD) and the development or worsening of Graves' ophthalmopathy (GO) is widely quoted but there has been no systematic review of the evidence.
Aims: We undertook a systematic review of randomized controlled trials (RCTs) to assess whether RAI for GD is associated with increased risk of ophthalmopathy compared with antithyroid drugs (ATDs) or surgery. We also assessed the efficacy of glucocorticoid prophylaxis in the prevention of occurrence or progression of ophthalmopathy, when used with RAI.
Methods: We identified RCTs regardless of language or publication status by searching six databases and trial registries. Dual, blinded data abstraction and quality assessment were undertaken. Random effects meta-analyses were used to combine the study data. Ten RCTs involving 1136 patients permitted 13 comparisons. Two RCTs compared RAI with ATD. Two RCTs compared RAI with thyroidectomy. Four RCTs compared the use of adjunctive ATD with RAI vs. RAI. Five RCTs examined the use of glucocorticoid prophylaxis with RAI.
Results: RAI was associated with an increased risk of ophthalmopathy compared with ATD [relative risk (RR) 4·23; 95% confidence interval (CI): 2·04-8·77] but compared with thyroidectomy, there was no statistically significant increased risk (RR 1·59, 95% CI 0·89-2·81). The risk of severe GO was also increased with RAI compared with ATD (RR 4·35; 95% CI 1·28-14·73). Prednisolone prophylaxis for RAI was highly effective in preventing the progression of GO in patients with pre-existing GO (RR 0·03; 95% CI 0·00-0·24). The use of adjunctive ATD with RAI was not associated with any significant benefit on the course of GO.
Conclusion: RAI for GD is associated with a small but definite increased risk of development or worsening of Graves' ophthalmopathy compared with ATDs. Steroid prophylaxis is beneficial for patients with pre-existing GO.
Radioiodine therapy (RAI) has been used in the treatment of Graves' disease (GD) for more than six decades but the association between RAI and developing or worsening of Graves' ophthalmopathy (GO) remains unclear. Several retrospective studies reported an association. However, others did not find a link. A recent questionnaire-based survey carried out by European Group on Graves' Orbitopathy (EUGOGO) found most responders used antithyroid drug (ATD) treatment as first-line therapy for Graves' hyperthyroidism if GO was present; however, after 6 months, if GO was still active, about 80% suggested the thyroid should be ablated. The negative attitude towards RAI has probably changed from the previous 1996 survey. Glucocorticoid prophylaxis is thought to be beneficial when used along with RAI, but routine use in all patients undergoing RAI is considered unnecessary by experts.
Although individual randomized controlled trials (RCTs) have suggested an increased risk of progression of ophthalmopathy after RAI, there has been no systematic review of the evidence. We have undertaken the first systematic review of RCTs to assess whether RAI for GD is associated with increased risk of occurrence or progression of ophthalmopathy, compared with ATD or surgery. We also assessed the role of glucocorticoid prophylaxis and adjunctive ATD in the prevention of occurrence or progression of ophthalmopathy, when used along with RAI.
Summary and Introduction
Summary
Background: An association between radioiodine therapy (RAI) for Graves' disease (GD) and the development or worsening of Graves' ophthalmopathy (GO) is widely quoted but there has been no systematic review of the evidence.
Aims: We undertook a systematic review of randomized controlled trials (RCTs) to assess whether RAI for GD is associated with increased risk of ophthalmopathy compared with antithyroid drugs (ATDs) or surgery. We also assessed the efficacy of glucocorticoid prophylaxis in the prevention of occurrence or progression of ophthalmopathy, when used with RAI.
Methods: We identified RCTs regardless of language or publication status by searching six databases and trial registries. Dual, blinded data abstraction and quality assessment were undertaken. Random effects meta-analyses were used to combine the study data. Ten RCTs involving 1136 patients permitted 13 comparisons. Two RCTs compared RAI with ATD. Two RCTs compared RAI with thyroidectomy. Four RCTs compared the use of adjunctive ATD with RAI vs. RAI. Five RCTs examined the use of glucocorticoid prophylaxis with RAI.
Results: RAI was associated with an increased risk of ophthalmopathy compared with ATD [relative risk (RR) 4·23; 95% confidence interval (CI): 2·04-8·77] but compared with thyroidectomy, there was no statistically significant increased risk (RR 1·59, 95% CI 0·89-2·81). The risk of severe GO was also increased with RAI compared with ATD (RR 4·35; 95% CI 1·28-14·73). Prednisolone prophylaxis for RAI was highly effective in preventing the progression of GO in patients with pre-existing GO (RR 0·03; 95% CI 0·00-0·24). The use of adjunctive ATD with RAI was not associated with any significant benefit on the course of GO.
Conclusion: RAI for GD is associated with a small but definite increased risk of development or worsening of Graves' ophthalmopathy compared with ATDs. Steroid prophylaxis is beneficial for patients with pre-existing GO.
Introduction
Radioiodine therapy (RAI) has been used in the treatment of Graves' disease (GD) for more than six decades but the association between RAI and developing or worsening of Graves' ophthalmopathy (GO) remains unclear. Several retrospective studies reported an association. However, others did not find a link. A recent questionnaire-based survey carried out by European Group on Graves' Orbitopathy (EUGOGO) found most responders used antithyroid drug (ATD) treatment as first-line therapy for Graves' hyperthyroidism if GO was present; however, after 6 months, if GO was still active, about 80% suggested the thyroid should be ablated. The negative attitude towards RAI has probably changed from the previous 1996 survey. Glucocorticoid prophylaxis is thought to be beneficial when used along with RAI, but routine use in all patients undergoing RAI is considered unnecessary by experts.
Although individual randomized controlled trials (RCTs) have suggested an increased risk of progression of ophthalmopathy after RAI, there has been no systematic review of the evidence. We have undertaken the first systematic review of RCTs to assess whether RAI for GD is associated with increased risk of occurrence or progression of ophthalmopathy, compared with ATD or surgery. We also assessed the role of glucocorticoid prophylaxis and adjunctive ATD in the prevention of occurrence or progression of ophthalmopathy, when used along with RAI.