Abstract #1400968: A Case of Co-Existing Alemtuzumab-Induced Thyroid Disorders

Abstract

Alemtuzumab (ALZ) is an anti-CD52 monoclonal antibody effective in treating relapsing-remitting Multiple Sclerosis (MS). ALZ is hypothesized to augment immune function due to mature lymphocyte depletion; it may also predispose patients to secondary autoimmune disorders during the immune system recovery phase, with thyroid dysfunction occurring in up to 33%. We a case of a woman with MS who developed Hashimoto’s thyroiditis followed by Graves’ disease after ALZ use. A 43-year-old woman with MS was referred for management of hyperthyroidism after experiencing 1 year of palpitations, insomnia, and tremors. She completed two doses of ALZ nineteen months apart. Nine months after her 2nd ALZ dose, she developed hypothyroidism (TSH 38 mIU/L, TPO 856 IU/L, and low FT4 0.2ng/dL); she was treated to euthyroidism with levothyroxine. Sixteen months after her 2nd dose, she developed hyperthyroidism, persisting after levothyroxine cessation: TSH 0.02 mIU/L, FT4 1.9ng/dL, FT3 7.4pg/mL, TRAb 9.6, TSI 385, and TPO 83 IU/L. Her Graves’ disease course was complicated by the development of mild unilateral proptosis and diplopia. Past medical history included neurogenic bladder and anxiety, treated with mirabegron and alprazolam. Family history was notable for thyroidectomy in her mother for unknown indication. Physical exam showed stable vitals, mild active thyroid eye disease, goiter, and fine bilateral hand tremor. She was initially treated with methimazole, but unfortunately developed significant hepatotoxicity. She was recommended for total thyroidectomy, which she underwent without complication following preparation with potassium iodide. This case highlights an interesting presentation of co-existing autoimmune thyroid disorders in an ALZ-treated patient. ALZ has a rapid and long-lasting effect on the immune system, leading to qualitative and quantitative lymphocyte changes. ALZ induced Graves’ disease (AIGD) is the most common thyroid disorder, followed by Hashimoto’s thyroiditis & silent thyroiditis at 63%, 15%, & 9%, respectively. Most of those with AIGD had overt symptoms, and 10% reported ophthalmopathy. They peak around 28 months after the last dose, concurring with the B cell slow recovery phase. Over half of patients with AIGD required anti-thyroid medications (56%), 22% underwent radioactive iodine, and 11% underwent thyroidectomy. Interestingly, MS patients who developed AIGD had better overall MS disease prognosis. The frequency of ALZ-associated thyroid disease underscores the importance of routine thyroid function monitoring every 3 months following ALZ, and a provision of thyroid education materials for earlier identification of thyroid disorders.