Graves’ Disease, a Late Complication of Chronic Graft vs Host Disease

Introduction: Graft-versus-host disease (GVHD), a complication of bone marrow transplant (BMT), occurs when the donor white blood cells attack the recipient’s host cells and can occur acutely or chronically several years post-transplant. It is very rare for chronic GVHD to cause hyperthyroidism due to Grave’s disease and thyrotoxicosis years after BMT. Hyperthyroidism after BMT is thought to occur by GVHD or by donor’s auto-reactive lymphocytes transferred to recipient, with majority of cases occurring with donors that have an underlying autoimmune thyroid condition. Case Report: We report a 62 year old male who presented with palpitations, tremors, sweating, weight loss, and anxiety for 3 weeks. Past medical history was significant for allogenic BMT due to AML 14 years ago, which was further complicated by GVHD of eye, liver and skin. Physical exam was negative for thyromegaly or thyroid tenderness. Initial work up showed TSH 0.03 (normal 0.4-5.0 MUI/l), free T4 3.32 (normal 0.6-1.2 ng/dl), TSI 194 % (normal <140 %). Ultrasound revealed a diffuse hypervascular thyroid gland with numerous avascular cystic areas in both lobes and increased homogenous, symmetrical uptake consistent with Graves’ disease was noted on radioactive iodine uptake scan. With clinical suspicion of GVHD leading to Graves’ disease with subsequent thyrotoxicosis, he was started on methimazole. However, due to persistent increase in transaminases, concern for agranulocytosis with methimazole, and risk of developing worsening GVHD of the skin or eye with radioactive iodine therapy, he underwent total thyroidectomy. His pathology showed bilateral lymphoepithelial lesions with florid follicular hyperplasia, marked monocytoid hyperplasia, and Germinal B cells positive for CD10 and negative for BCL2. Lymphoepithelial lesions can be seen in chronic lymphocytic thyroiditis due to persistent inflammation. Conclusion: This case raises the question on the etiology of thyroid nodules and Graves’ disease occurring after BMT. We believe that his pathology findings may be due to chronic GVHD. Hyperthyroidism after BMT is extremely rare, with only a few case reports documenting this phenomenon. We believe that our patient developed hyperthyroidism 14 years after BMT most likely as a sequela of chronic GVHD with underlying immune dysregulation leading to formation of TSI and thyroiditis due to cellular invasion. This suggest a multifactorial etiology of hyperthyroidism in patients with GVHD. However, more prospective studies are required to the explain etiology of hyperthyroidism in GVHD. Moreover, such patients should be closely monitored for development of thyroid dysfunction or thyroid nodules.