Autoimmune Thyroid Disease in Islet Transplant Recipients Discontinuing Immunosuppression Late After Lymphodepletion

Clinical islet transplantation (CIT) is an innovative strategy to treat highly selected individuals with type 1 diabetes mellitus (T1DM). Lymphodepletion with alemtuzumab or thymoglobulin is often used for induction therapy in CIT. Alemtuzumab was recently licensed as a treatment of relapsing remitting multiple sclerosis (RRMS). In RRMS, autoimmune thyroid disease (AITD) has developed in up to 40% of individuals treated with alemtuzumab. The appearance of AITD after CIT is not well described. We herein explore factors associated with AITD developing after CIT and any relationship with exposure to lymphodepleting antibodies (alemtuzumab or thymoglobulin).

Five cases of AITD developing after CIT for T1DM are described. All were female. Four cases had received alemtuzumab (20 to 40 mg) prior to at least one islet infusion, and one received thymoglobulin induction. The presentation with AITD was 18 to 135 months after first transplant and 11 to 18 months after withdrawal of all maintenance immunosuppression (IS). Four cases presented with clinical and biochemical evidence of hyperthyroidism from Graves disease. One case presented with biochemical evidence of hypothyroidism and positive TSH receptor antibodies. All were treated with conventional therapies for AITD.

Despite routine use of alemtuzumab, clinical presentations of AITD seem to be uncommon in patients with CIT receiving IS. However, AITD can develop after withdrawal of IS, highlighting the need for careful thyroid surveillance in this population.