Graves' orbitopathy (GO) is a disfiguring and disabling disease that profoundly impairs the quality of life of affected patients. High dose intravenous (iv) glucocorticoids (GC) (ivGC) is a well established, widely used treatment for active GO. The use of systemic glucocorticoids takes advantage from their immune suppressive and antiinflammatory actions, resulting in an overall beneficial effect ranging from \~35 to \~60% of patients in various studies. The intravenous route of administration has been shown to be superior to the oral route, both in terms of GO outcome and side effect profile. The combination of ivGC and orbital radiotherapy (OR) is used routinely in patients with moderate-severe, active GO, as a second-line treatment, as also recommended in the recent Guidelines published by the European Thyroid Association/European Group on Graves' Orbitopathy. Thus, the majority of studies have shown that OR increases the response rate to GC. Those studies were performed using oral GC, whereas it is not known whether OR potentiate also the effects of ivGC.
The present study is aimed at determining whether OR potentiate the effects of ivGC in the treatment of moderately severe and active GO, in terms of GO outcome and quality of life. A possible extension of the study can be foreseen, aimed at investigating the very long time GO outcome.
A diagnosis of Graves' disease based on the presence of hyperthyroidism (either untreated or treated with antithyroid drugs) associated with detectable anti-TSH receptor autoantibodies
No major treatments for hyperthyroidism (thyroidectomy or radioiodine) in the last 3 months
Euthyroidism on anti-thyroid medications or L'thyroxine (LT4) since at least 2 months
GO symptoms lasting since no more than one year
Absence of Graves' hyperthyroidism (present or past)
Thyroidectomy or radioiodine in the last 3 months
Uncontrolled hyperthyroidism or hypothyroidism
GO symptoms lasting since more than one year
Parallel
Orbital radiotherapy
RadiationA high-voltage linear accelerator will be used and a cumulative radiation dose of 20 Gy will be delivered to each eye in 10 fractionated doses over a period of 2 weeks. All patients will be treated in both eyes.
Methylprednisolone
DrugMethylprednisolone pulse therapy for 12 weeks as follows: 500 mg IV once weekly for 6 weeks, then 250 mg IV once weekly for a further 6 weeks. Cumulative dose 4.5 g.
Comparison of overall GO outcome determined using a composite evaluation
A composite evaluation of GO was described previously. Improvement is defined as amelioration of two parameters in at least one eye, without deterioration of any parameters in both eyes: Deterioration is defined as worsening in two parameters in at least one eye: All other cases are defined as "no change" The parameters are: * Eyelid swelling (improvement/worsening according to EUGOGO Atlas evaluation) * Lid aperture in mm (significant variation: 2 or more mm) * Clinical activity score (CAS) (7 items: spontaneous pain, evoked pain, eyelid edema, eyelid redness, conjunctiva redness, caruncle edema, chemosis; significant change: at least 2 points) * Exophthalmos in mm (significant variation 2 or more mm) * Eye muscle involvement - diplopia score (Gorman score) (significant variation: disappearance or change in the degree, or improvement of ≥12 degrees in motility)
Comparison of overall GO outcome determined using a composite evaluation
A composite evaluation of GO was described previously. Improvement is defined as amelioration of two parameters in at least one eye, without deterioration of any parameters in both eyes: Deterioration is defined as worsening in two parameters in at least one eye: All other cases are defined as "no change" The parameters are: * Eyelid swelling (improvement/worsening according to EUGOGO Atlas evaluation) * Lid aperture in mm (significant variation: 2 or more mm) * Clinical activity score (CAS) (7 items: spontaneous pain, evoked pain, eyelid edema, eyelid redness, conjunctiva redness, caruncle edema, chemosis; significant change: at least 2 points) * Exophthalmos in mm (significant variation 2 or more mm) * Eye muscle involvement - diplopia score (Gorman score) (significant variation: disappearance or change in the degree, or improvement of ≥12 degrees in motility)
Comparison of a disease specific quality of life questionnaire (GO-QoL)
Comparison of a disease specific quality of life questionnaire (GO-QoL)
GO relapse
GO worsening in comparison with the 26 week evaluation, by a composite GO score: Worsening is defined as worsening in two parameters in at least one eye: The parameters are: * Eyelid swelling (worsening according to EUGOGO Atlas evaluation) * Lid aperture in mm (significant worsening: 2 or more mm) * Clinical activity score (CAS) (7 items: spontaneous pain, evoked pain, eyelid edema, eyelid redness, conjunctiva redness, caruncle edema, chemosis; significant worsening: at least 2 points) * Exophthalmos in mm (significant worsening: 2 or more mm) * Eye muscle involvement - diplopia score (Gorman score) (significant worsening: appearance or change in the degree, or worsening of ≥12 degrees in motility)
Comparison of a disease specific quality of life questionnaire (GO-QoL)
Comparison of a disease specific quality of life questionnaire (GO-QoL)
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