The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy

Abstract

Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). Choice of treatment should be based on 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, intravenous (iv) 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 counselling, a combination of iv methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 grams (g) of iv methylprednisolone in 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) a second course of iv 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 iv glucocorticoids, d) teprotumumab; e) rituximab and f) tocilizumab. Sight threatening GO is treated with several high single doses of iv 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.

Response to comment by Smith on the 2021 EUGOGO guidelines

“…The authors of this response are in line with Dr Smith that the antiinsulin-like growth factor 1 receptor inhibiting monoclonal antibody, teprotumumab is a very promising drug for the management of active and moderate-tosevere GO (8), and this is repeatedly and clearly stated in the text part, the table of recommendations, and in the legend of box three (2). However, guidelines are 'made for everybody', offering evidence-based recommendations, which should be possible to apply and follow worldwide.…”

“…Thank you for giving us the opportunity to respond to the comment of Dr Smith (1) on 'The 2021 EUGOGO guidelines for the medical management of Graves' orbitopathy (GO)' (2).…”

“…These guidelines, officially endorsed by the European Society of Endocrinology and unanimously supported by the international consortium 'European Group on Graves' orbitopathy, EUGOGO' encompassing 25 expert centers on GO, aimed to mirror the current evidencebased management of this complex disease (2). Although far from optimal, both i.v.…”

Non-Conventional Clinical Uses of TSH Receptor Antibodies: The Case of Chronic Autoimmune Thyroiditis

“…Interestingly 30/44 (68.2%) of patients with CAT and TAO had TSAb positive values, while only 36/656 (5,5%) of patients with CAT and no TAO were TSAb positive; even more significant, all the 15 patients with active/severe disease had positive TSAb values. Although cases of severe thyroid-associated orbitopathy have been documented in Hashimoto's thyroiditis (46), the recently published Guidelines for the medical management of TAO (47) suggest the opportunity to assay TRAb in all patients with TAO and either Graves' disease or Hashimoto's thyroiditis for diagnostic and prognostic purposes.…”

Comment on the 2021 EUGOGO Clinical Practice Guidelines for the Medical Management of Graves’ Orbitopathy

“…I am writing to you after reading the article entitled 'The 2021 European Group on Graves' Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves' Orbitopathy' by Bartalena et al. (1). In these guidelines, the authors advise their colleagues who care for patients with Graves' orbitopathy (GO) to consider an aggregate of several factors in determining the optimal therapy for moderate to severe and/or sightthreatening GO.…”