P-79 Graves’ Disease associated with alemtuzumab use for multiple sclerosis

Abstract

Abstract Introduction Alemtuzumab was the first humanized monoclonal antibody to be created and is directed against CD52, a lymphocyte cell surface marker of unknown function. It has been used to treat leukemia and organ transplant rejection. More recently, alemtuzumab has been demonstrated to be highly effective in treating relapsing-remitting multiple sclerosis (MS) disease. Thyroid disease develops in approximately 20% of patients using alemtuzumab for MS, and Graves’ disease is the most common among them. Graves’ disease has not been reported in the use of alemtuzumab for reasons other than MS. Clinical Case A 28-year-old female patient with a 10 year history of MS had been treated with pulse corticosteroid, β-interferon and fingolimod. She received alemtuzumab in May 2019 due to increased relapse rates. After the first dose of alemtuzumab, she could not continue her treatment program due to the COVID-19 pandemic. Thyrotoxic thyroid functions (TSH: <0.015 uIU/mL, free T4: 24.79 pmol/L) were detected in the laboratory examination of the patient who was admitted to the endocrinology outpatient clinic with the complaint of palpitation in April 2021. The review of the patient's past laboratory test results determined she was euthyroid before alemtuzumab treatment. She had no personal or family history of thyroid disease. She had no signs and symptoms of thyroid ophthalmopathy. Ultrasonographic examination of her thyroid gland revealed normal size gland and pseudonodular appearance in the parenchyma. Subsequent thyroid scintigraphy showed diffuse uptake of the radioisotope and reduced counting time of the examination. These results were consistent with Graves’ disease. The patient was started on 5 mg methimazole twice a day. Since the etiology of Graves’ disease was thought to be primarily related to alemtuzumab, the patient's MS treatment was continued with ocrelizumab. She stopped the methimazole treatment within 3 months and did not regularly show up to her follow-up visit. In November 2022, she was admitted to the outpatient department with palpitation, sweating, and irritability symptoms. Thyrotoxic thyroid functions were detected again (TSH:<0,015 uIU/mL, free T4: 26,82 pmol/L). She was restarted on 5 mg methimazole treatment twice a day. In June 2023, she was euthyroid (TSH: 0,496 uIU/mL, free T4: 5,42 pmol/L, free T4: 10,45 pmol/L) and her TSI level was undetectable. The methimazole was reduced to 5 mg once a day. She continues to her treatment and follow-up in our center. Conclusion Graves’ disease is a common complication of alemtuzumab use in MS. Alemtuzumab-associated Graves’ disease follows an atypical course compared to the classical form of the disease. The spontaneous remission rate is less than in the classical form of the disease, and medical treatment is often required. Thyroidectomy may be necessary in cases that do not respond to antithyroid agents. Close monitoring of thyroid function tests is essential in alemtuzumab-associated Graves’ disease.