Reactivation after total thyroidectomy? A thyroid eye disease case that challenges established clinical paradigms

Summary: Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves' disease, with an incidence of approximately 1.9 cases per 10,000 inhabitants per year. Its pathophysiology involves an autoimmune response mediated by TSH receptor antibodies (TRAbs), leading to inflammation, fibroblast activation, and orbital tissue remodeling. Although TED typically becomes inactive within 1-3 years, 5-10% of patients experience recurrences. Persistence or reactivation after total thyroidectomy is uncommon, and published reports remain limited. We report a 56-year-old man with Graves' disease diagnosed in 2020 and multiple TED reactivations treated with intravenous methylprednisolone. In 2022, he was diagnosed with low-risk papillary thyroid carcinoma (T1a N0 M0) and underwent total thyroidectomy; radioiodine therapy was withheld due to orbitopathy. Despite complete surgery, he developed a new reactivation in November 2023. In March 2025, he presented with ocular pain; active TED was confirmed with a CAS of 6/7 and moderate-to-severe EUGOGO classification. Laboratory tests revealed positive TRAbs and suppressed TSH. A multidisciplinary team recommended another steroid course followed by tocilizumab. TED reactivation after thyroidectomy is rare and challenges the rationale of antigen removal. Possible mechanisms include microscopic residual thyroid tissue or persistent TRAb activity. Similar reports are limited, and this appears to be the first case described in Colombia. This case highlights the need for multidisciplinary management and the potential role of immunomodulators such as tocilizumab in refractory post-thyroidectomy TED. Further research is needed to clarify factors contributing to disease persistence. Learning points: TED reactivation can occur even after total thyroidectomy, challenging the traditional belief that removing the thyroid eliminates antigenic stimuli. Persistently elevated TRAb levels or microscopic residual thyroid tissue may contribute to post-surgical disease activity. Early thyroidectomy does not guarantee sustained TED remission, especially in cases with severe or recurrent activity. Multidisciplinary involvement is essential, particularly in complex cases involving both autoimmune disease and thyroid carcinoma. Tocilizumab represents a valuable second-line option for TED refractory to glucocorticoids, aligning with emerging evidence for immunomodulatory therapies. This is the first case reported in Colombia with these clinical characteristics, highlighting the rarity and importance of awareness.