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Rosa M. García-Moreno Endocrinology and Nutrition Department, Hospital Universitario La Paz, Madrid, Spain

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Cristina Escabias Nuclear Medicine Department, Hospital Universitario La Paz, Madrid, Spain

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Cristina Utrilla Radiology Department, Hospital Universitario La Paz, Madrid, Spain

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Elena Ruiz-Bravo Pathology Department, Hospital Universitario La Paz, Madrid, Spain

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Margarita Sánchez Ophthalmology Department, Hospital Universitario La Paz, Madrid, Spain

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Beatriz Lecumberri Endocrinology and Nutrition Department, Hospital Universitario La Paz, Madrid, Spain

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Background: Orbital radioiodine uptake in patients with thyroid cancer is very uncommon with only a few reported cases, most of them being metastasis. The accumulation of <sup>131</sup>I in nonthyroidal tissues and body fluids can lead to false-positive results in scintigraphy, which are sometimes difficult to differentiate from true metastases. Case Report: A post-therapy <sup>131</sup>I whole-body (WBI) scintigraphy in an asymptomatic 57-year-old female with papillary thyroid carcinoma (PTC) previously treated with total thyroidectomy and 6 ablative radioiodine doses showed a focal uptake in the right eyeball region. The lesion, placed in the orbital space, was surgically removed, and histology revealed a conjunctival inclusion cyst. Discussion: Ocular and orbital metastases from thyroid cancer, as well as some non-neoplastic disorders or contamination, are possible causes for <sup>131</sup>I uptake in the orbital region in scintigraphy. Conjunctival inclusion cyst is a condition associated with incidental <sup>131</sup>I uptake that had not been reported before and should be ruled out as a non-metastatic cause of orbital radioiodine uptake in patients with PTC.

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Ilaria Muller Thyroid Research Group, Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom

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Carla Moran Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom

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Beatriz Lecumberri Department of Endocrinology and Nutrition, La Paz University Hospital, IdiPAZ, Autonomous University of Madrid, Madrid, Spain

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Brigitte Decallonne Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

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Neil Robertson Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom

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Joanne Jones Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom

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Colin M. Dayan Thyroid Research Group, Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom

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Thyroid dysfunction (TD) frequently occurs as an autoimmune complication of immune reconstitution therapy (IRT), especially in individuals with multiple sclerosis treated with alemtuzumab, a pan-lymphocyte depleting drug with subsequent recovery of immune cell numbers. Less frequently, TD is triggered by highly active antiretroviral therapy (HAART) in patients infected with human immunodeficiency virus (HIV), or patients undergoing bone-marrow/hematopoietic-stem-cell transplantation (BMT/HSCT). In both alemtuzumab-induced TD and HIV/HAART patients, the commonest disorder is Graves’ disease (GD), followed by hypothyroidism and thyroiditis; Graves’ orbitopathy is observed in some GD patients. On the contrary, GD is rare post-BMT/HSCT, where hypothyroidism predominates probably as a consequence of the associated radiation damage. In alemtuzumab-induced TD, the autoantibodies against the thyrotropin receptor (TRAb) play a major role, and 2 main aspects distinguish this condition from the spontaneous form: (1) up to 20% of GD cases exhibit a fluctuating course, with alternating phases of hyper- and hypothyroidism, due to the coexistence of TRAb with stimulating and blocking function; (2) TRAb are also positive in about 70% of hypothyroid patients, with blocking TRAb responsible for nearly half of the cases. The present guidelines will provide up-to-date recommendations and suggestions dedicated to all phases of IRT-induced TD: (1) screening before IRT (recommendations 1–3); (2) monitoring during/after IRT (recommendations 4–7); (3) management of TD post-IRT (recommendations 8–17). The clinical management of IRT-induced TD, and in particular GD, can be challenging. In these guidelines, we propose a summary algorithm which has particular utility for nonspecialist physicians and which is tailored toward management of alemtuzumab-induced TD. However, we recommend prompt referral to specialist endocrinology services following diagnosis of any IRT-induced TD diagnosis, and in particular for pregnant women and those considering pregnancy.

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