Endocrine Abstracts

Introduction: The 2021 EUGOGO guidelines suggest first-line treatment for Dysthyroid Optic Neuropathy (DON) to consist of high-dose intravenous methylprednisolone treatment. However, this often needs to be combined with orbital decompression surgery. Here, we present a case of steroid-resistant DON treated with Teprotumumab in a subject who declined orbital decompression.

Methods: A 56-year old male treated for Graves hyperthyroidism with a standard block-replace regimen developed Thyroid Eye Disease (TED) three months after treatment initiation. His initial Clinical Activity Score (CAS) was 2 and progressed to 6 within that timeframe with associated papilledema of the right eye. Because no alternative aetiology of the papilledema was identified, this was considered part of the TED which was thus diagnosed as DON. Corticosteroid pulse therapy was administered twice without clinically significant response. In line with the current EUGOGO guidelines for DON, orbital decompression surgery was proposed but was declined by the patient. Alternative treatment with the anti-IGF-1R monoclonal antibody Teprotumumab was made available through early access program.

Results: Teprotumumab infusion resulted to improved vision and partial regression of the papilledema from the first dose. During subsequent treatments, his CAS decreased to 0, proptosis drastically improved and papilledema regressed completely. Thyroid-stimulating immunoglobulin level declined steadily during treatment but remained positive (TSI: 4.23 U/l; reference: < 1.75 U/l) about six weeks after the last dose of Teprotumumab. Baseline HbA1c was 5.3%, peaked at 6.1% and declined at 5.8% six weeks post-treatment without glucose lowering therapy other than lifestyle measures. The patient experienced transient tinnitus after the first dose of teprotumumab; control audiometry ruled-out treatment-related hearing impairment.

Conclusion: We describe a case of steroid-resistant TED with features of DON treated successfully with teprotumumab. This suggest that IGF-1R targeting therapy could be used as second-line therapy in steroid-resistant DON before considering surgery. Robust assessment of treatment-response and recurrence rate in randomized clinical trials is nonetheless needed.

Referencees: 1. Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, Marinò M, Vaidya B, Wiersinga WM; EUGOGO †. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur. J. Endocrinol. 185, G43–G67 (2021). 2. Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marinò M, Antonelli A, Dailey R, Harris GJ, Eckstein A, Schiffman J, Tang R, Nelson C, Salvi M, Wester S, Sherman JW, Vescio T, Holt RJ, Smith TJ. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N. Engl. J. Med. 382, 341–352 (2020).

Keywords: Thyroid Eye Disease, Dysthyroid Optic Neuropathy, Teprotumumab