Endocrine Abstracts

Introduction: Graves Disease (GD) is an autoimmune disease, in which CD4+ Th2 cells secrete interleucin-4 (IL-4) and IL-5 and activate antibody production. IL-4 has been considered a therapeutic target for treatment of immune-related diseases, by enhancing and redirecting T and B cell function. Dupilumab, a monoclonal antibody, inhibits IL-4 and IL-13 and is currently used for treatment of atopic dermatitis, nasal polyposis and asthma. There is a single case report of painless thyroiditis as an adverse effect of dupilumab.

Case Report: We report a case of a 47-year male with history of a severe nasal polyposis. He was treated with corticosteroids, with only mild improvement. In March 2022 he was started on dupilumab 600 mg followed by 300 mg every 2 weeks. At 6-8 weeks of treatment, he complained of irritability, weight loss and heat intolerance. In October 2022, laboratory studies revealed thyrotoxicosis, with TSH 0.01 µU/mL (0.27-4.2) and free T4 (FT4) 29.5 µg/dL (12-22). He was started on methimazole 15 mg/day in December 2022 by his family physician and was sent to the Endocrinology Department. At observation, he had no neck discomfort, compressive symptoms, or exophthalmos. Laboratory tests showed TSH <0.008 µU/ml, FT4 12.9 µg/dl, FT3 4.92 pg/ml (3.10-6.8), TRAb 3.17 U/l (<1.58 U/l), which confirmed the diagnosis of GD. Thyroid ultrasound revealed an enlarged thyroid gland, with heterogeneous echogenicity, but no nodules or cervical adenopathies. He currently maintains treatment with methimazole 10 mg/day and dupilumab 300 mg every 2 weeks.

Discussion: To the best of our knowledge, this is the first case ever reported of dupilumab-related GD. The suppression of Th2 cells through inhibition of IL-4 and IL-13 by dupilumab amplifies the Th1 pathway. In GD, the predominant patoghenic TSH receptor autoantibody is IgG1 isotype response, which is stimulate by Th1 cytokines. An increased Th1/Th2 ratio may promote the development of GD by dupilumab. More studies are needed to explain the underlying mechanism of this adverse effect. Thyroid function tests before treatment with dupilumab and during follow-up may be useful.