7865 Thyroid Acropachy: A Clinical Response to Teprotumumab

Abstract Disclosure: J. Lira: None. M. Zaidi: None. S. Kim: None. Background: Thyroid acropachy is a rare extrathyroidal manifestation of Graves disease (1). Due to its rarity, generally benign clinical course and the limited understanding of its pathophysiology, there is currently no specific treatment for thyroid acropathy. Clinical Case: A 25-year-old Asian male with a history of Graves disease, for which he had undergone total thyroidectomy 2 years prior, presented with worsening double vision. The patient also complained of swelling in the legs, and pain and stiffness in his hands and feet. On exam, he displayed bilateral asymmetric proptosis, conjunctival injection, and lid lags. Nodular and plaque-like lesions with non-pitting edema were observed on both pretibial skin. The fusiform swelling of fingers and prominent clubbing of finger- and toe-nails was noted. Upon further questioning, he admitted to smoking at least a pack of cigarettes a day. His laboratory findings were as follows: TSH 0.40 uIU/ml (0.4 - 4.2) with levothyroxine supplement, thyrotropin receptor Ab (TRAB) 81.1 IU/L (0.0 - 1.75), which was significantly elevated compared with 34.6 IU/L right after thyroidectomy. A skin biopsy was performed, revealing well-differentiated myxomatous lesion involving dermis and subcutaneous fat, with a splaying of the collagen by abundant mucin representing hyaluronic acid, confirming thyroid dermopathy. Bilateral hand X-rays showed soft tissue swelling and extensive bilateral periostitis and subperiosteal bone formation in metacarpals and phalanges, consistent with thyroid acropachy. After showing non-response to a trial of Prednisone, Teprotumumab was initiated for Graves ophthalmopathy. The patient was advised to quit smoking. Following five infusions, significant improvement was observed in proptosis and orbital inflammation. The pretibial myxedematous lesion also improved. Furthermore, there was a marked decrease in swelling in bilateral metacarpals and phalanges with regaining full range of motion. All extrathyroidal manifestations further improved after the completion of a total of eight infusions of Teprotumumab, with TRAB levels down to 14.3 IU/L. Conclusion: Our case is the first example demonstrating clinical improvement in patients with thyroid acropathy following Teprotumumab treatment. This observation implies that the pathophysiology of thyroid acropathy encompasses the interplay between TSH receptor and IGF-1 receptor signaling, akin to Grave ophthalmopathy, and suggests that the direct skeletal effect of TSH may be caused by the interaction with IGF-1 pathway, as shown in pre-clinical study (2). Reference: (1) Fatourechi V et al, J Clin Endocrinol Metab. 2002 (2) Boutin A et al, Front Endocrinol (Lausanne). 2020 Presentation: 6/1/2024