FRI554 Pretibial Myxedema Associated With Hashimoto Thyroiditis Treated With Teprotumumab

Disclosure: E.M. Niedzialkowska: None. B. Ajaz: None. A. Pokharel: None. Introduction: Pretibial myxedema (PTM) is a localized thyroid-associated dermopathy characterized by local thickening of the skin of the lower extremities. It mostly develops after the onset of thyroid eye disease (TED). Majority of the cases are associated with Graves disease (GD) but infrequently it can occur in Hashimoto thyroiditis (HT) in the presence of thyroid stimulating immunoglobulins (TSIs). Orbital fibroblasts and the pretibial dermis share antigenic sites that underlie autoimmune thyroid disease. IGF-1 has been reported to potentiate the effects of TSH and TSI on TSHR signaling and fibroblast proliferation. Teprotumumab, a novel monoclonal antibody that blocks IGF-1R receptors, is registered for TED treatment. It is plausible it also improves outcomes in PTM through the same mechanism. Clinical case: 52 year old female reported to our Endocrinology clinic with proptosis and myxedema. The patient was diagnosed with hypothyroidism at the age of 21 and was on substitutional dose of levothyroxine, 125 mcg daily. She developed TED 7 years prior with bilateral exophthalmos with medial rectus muscle infiltration. She underwent 5 decompression surgeries and steroid courses due to concern for optic nerve compression. 4 years prior to the visit she developed bilateral, erythematous pitting edema of the lower extremities with involvement of the pretibial areas, ankles and toes and underwent excess left toe callus excision. Despite multiple courses of intralesional steroid injections and topical ammonium lactate use the patient reported persistent edema, pruritus, and restriction of motion. Laboratory results were significant for TSH of 1.73 uIU/mL (n 0.40 - 4.50 uIU/mL), TRAB >40 IU/L (0.00 - 1.75 IU/L), TSI 4.95 (n <0.10 IU/L), TPO antibody <=35 IU/mL, free ft3 2.5 pg/ml (1.7 - 3.7 pg/mL), free ft4 1.0 (0.7 - 1.5 ng/dL). The patient underwent thyroidectomy with pathology results consistent with Hashimoto thyroiditis (thyroiditis with thyroid follicles, Hurthle cell change, marked lymphoid and fibroadipose tissue). Following the procedure she experienced PTM and TED flare up. Subsequent orbital decompression and orbital steroid injections provided minimal improvement. The patient was started on Teprotumumab (8 infusions every 3 weeks) with marked improvement of orbitopathy (CAS reduction from 6/10 to 1/10) and significant reduction of lower extremity edema and rash. Conclusion: We present the case of Hashimoto thyroiditis associated with TED with PTM successfully treated with Teprotumumab. In TED, TSI binds to IGF-1R creating a complex that promotes orbital inflammation. Teprotumumab is believed to degrade antibody-receptor complex and downregulate fibroblast activation and glycosaminoglycans deposition. We postulate the same process may occur in dermal fibroblasts in the light of PTM improvement after teprotumumab treatment. Presentation: Friday, June 16, 2023