Guidelines for medical management of GO - EUGOGO 2021 - Clinical Practice Guideline

Sep 30, 2026

Graves’ orbitopathy (GO) is the major extrathyroidal manifestation of Graves’ disease, and treatment choice depends on clinical activity and disease severity. Early referral to specialized centers is emphasized, with risk factor assessment including smoking, thyroid dysfunction, thyrotropin receptor antibody levels, radioactive iodine (RAI) exposure, and hypercholesterolemia. Control of risk factors and local therapies plus selenium are usually sufficient in mild active GO, while RAI-selected patients may require low-dose oral prednisone prophylaxis. For moderate-to-severe active or sight-threatening GO, antithyroid drug-based management of hyperthyroidism is central, and first-line therapy recommends i.v. methylprednisolone combined with mycophenolate sodium (optimal cumulative 4.5 g).

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CategoryHealthcare

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Pages25

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European Journa l of Endocrinology |

L Bartalena, GJ Kahaly and others
Guidelines for medical management of GO
185:4
G43–G67
Clinical Practice Guideline | | | --- | --- | | The 2021 European Group on Graves’orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy
L Bartalena1,*, GJ Kahaly2,*, L Baldeschi3, C M Dayan4, A Eckstein5, C Marcocci6, M Marinò6, B Vaidya7 and W M Wiersinga8 on behalf of EUGOGO†
1Department of Medicine and Surgery, University of Insubria, Varese, Italy, 2Department of Medicine I, Johannes Gutenberg-University (JGU) Medical Center, Mainz, Germany, 3Department of Ophthalmology, Cliniques Universitaires Saint Luc, Catholic University of Louvain, Brussels, Belgium, 4Thyroid Research Group, Cardiff University School of Medicine, Cardiff, UK, 5Clinic for Ophthalmology, University Clinic, Essen, Germany, 6Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, 7Department of | | | Endocrinology, Royal Devon & Exeter Hospital and University of Exeter Medical School, Exeter, UK, and 8Amsterdam University Medical Center, Amsterdam, the Netherlands
*(L Bartalena and GJ Kahaly contributed equally to this work and share first authorship)
†(List of EUGOGO members who collaborated for this Guideline is provided in the Acknowledgements section) | Correspondence should be addressed to G J Kahaly
Email
[gkahaly@uni-mainz.de](gkahaly@uni-mainz.de) | Abstract Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD) . Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves’hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolonein 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation,(b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids,(d) te protumumab; (e) rituximab and (f) tocilizumab. Sightthreatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations. European Journal of Endocrinology (2021) 185, G43–G67 | [https://eje.bioscientifica.com](https://eje.bioscientifica.com)
[https://doi.org/10.1530/EJE-21-0479](https://doi.org/10.1530/EJE-21-0479) | © 2021 European Society of Endocrinology Printed in Great Britain | | --- | --- | Published by Bioscientifica Ltd. This Guideline is endorsed by the

FAQs

How should treatment for Graves’ orbitopathy (GO) be selected?

Treatment should be based on assessment of GO clinical activity and severity. Early referral to specialized centers is fundamental for most patients with GO.

Which risk factors should be evaluated in GO?

Risk factors include smoking, thyroid dysfunction, high serum thyrotropin receptor antibody levels, radioactive iodine (RAI) treatment, and hypercholesterolemia.

What is the recommended first-line regimen for active moderate-to-severe GO?

A combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line therapy. The optimal regimen is a cumulative i.v. methylprednisolone dose of 4.5 g in 12 weekly infusions.

Sep 30, 2026

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