An Interesting Case of Euthyroid Graves’ Ophthalmopathy, With Negative Thyroid-Stimulating Hormone Receptor Antibodies

Abstract

Thyroid eye disease (TED), also known as Graves' orbitopathy or ophthalmopathy (GO) or Graves' eye disease, is an autoimmune condition of the retroocular tissues associated with Graves' disease. In isolated GO, the patient can present without thyroid hormone dysfunction or systemic symptoms of Graves' disease, in which case it is called euthyroid Graves' ophthalmopathy (EGO). It is very rare for this condition to have negative thyroid-stimulating hormone receptor (TSHR) autoantibodies, and we present such a rare case of a young female, who had progressive bilateral vision loss, intermittent left-sided retroocular headache, and severe bilateral proptosis. The patient was diagnosed with EGO based on multidisciplinary consults, diagnostic orbital magnetic resonance imaging (MRI) results, and a good response to treatment with intravenous steroids. Later, the patient was followed as an outpatient and treated with thyroid orbitopathyspecific immunotherapy with teprotumumab. The patient's response to teprotumumab was excellent and caused significant improvement in visual acuity, proptosis, and chemosis. This adds valuable literature to the medical field and gives insight to clinicians to consider the diagnosis of GO even with seronegative TSHR autoantibodies and euthyroid hormone status. It also adds to the understanding of the complex pathophysiology of this rare condition.

Monoclonal Antibodies for the Treatment of Graves Orbitopathy: Precision Medicine?

“…25–101 The literature on the use of Mabs for treating GO has been centered on blockage of IL-6 (Tocilizumab), 34,39,41,49,50,53,56,58–60,63,64,68–72,79,80,84,87,90,96–98 anti-CD20 lymphocytes (Rituximab), 26–33,35,37,38,40,42–48,51,54,55,61,62,65,67,73,89 and IGF1R (Teprotumumab). 52,66,74–78,82,85,86,88,91,92,94,95,99–101 Three articles have described Mabs that block TNF-α, 25,36,83 and one article has described Mabs that block the B-lymphocyte stimulator (BLyS) protein (Belimumab). 81 Blockage of TSHR with a Mab named K1-70 has been recently described in two case series.…”

“…26,27,30,33,35,37,[42][43][44][46][47][48]54,55,61,62,65,67,73,89 In contrast, Teprotumab has only been tested in the USA. [74][75][76][77][78]82,85,86,88,91,92,94,95,99,100,102 Most articles on the three most tested Mabs consist of case reports and case series (Tables 2-4). Rituximab has been the most frequently used in published studies and has been tested in 290 patients described in 11 case reports and 13 case series (Table 2) as well as four randomized clinical trials (Table 5).…”

“…In several case reports and case series, there was no collateral effects 31,32,38,39,45,46,48,51,53,60,64,87,88 or they were not stated. 27,40,50,56,[69][70][71]73,76,78,86,90,95,100,102 Some collateral effects depended on the drug that was being used (Table 6). For instance, hyperlipidemia and neutropenia were common with Tocilizumab, 80,84,97 and infusion-related reactions (rash, cytokines release syndrome, bronchospasm, and erythroderma) and hypotension were the main concern with Rituximab.…”

“…26,27,30,33,35,37,42–44,46–48,54,55,61,62,65,67,73,89 In contrast, Teprotumab has only been tested in the USA. 74–78,82,85,86,88,91,92,94,95,99,100,102…”