Graves Disease Due to Immune Reconstitution on Alemtuzumab Therapy

Alemtuzumab is a CD52 monoclonal antibody approved for the treatment of multiple sclerosis. Autoimmune thyroid dysfunction can occur in 20-30% of patients receiving the drug. We report here a case of Alemtuzumab induced Graves disease that developed after 29 months since the start of the medication.

Case Description:

A 45-year-old male with family history of unknown thyroid disorder, presented to our clinic with symptoms of tachycardia, un-intentional weight loss, heat intolerance and hyper-defecation in May 2021. No prior thyroid lab results were available. Interestingly, he received 3 infusions of Alemtuzumab for multiple sclerosis in the past 2.5 years with the last infusion 12 months back. Blood work showed a suppressed TSH 0.01 uIU/mL (0.35-4.94 uIU/mL), an elevated free T4 3.78 ng/dL (0.7-1.32 ng/dL), free T3 was >20 pg/mL (2.3-4.2 pg/mL), the thyroid stimulating immunoglobulin (TSI) was >40 IU/L ( <0.5 IU/L) and normal serum chemistry and liver tests. Bedside thyroid ultrasound revealed hypervascularity with diffuse heterogeneity without any discrete nodules. Thyroid uptake and scan with 292 mCi 123-Iodine showed increased 1-hour and 24-hour uptake at 63% and 67% respectively. Diagnosis of Graves disease was made and treatment with methimazole 5 mg one tab twice a day and propranolol 10 mg twice a day was initiated. At 3-months follow up, sympatho-adrenergic symptoms had resolved and there was improvement in all hyperthyroid symptoms. Repeat free T4 had decreased to 2.04 ng/mL with a suppressed TSH. Methimazole and beta-blocker therapy were continued at this point and close follow up was recommended.

Discussion:

Thyroid autoimmunity can occur on Alemtuzumab therapy due to immune reconstitution from dysregulation of T lymphocytes with an onset ranging from 6-60 months. Susceptibility to develop Graves’ disease is common, with an incidence of 60-70% in such patients. It is pertinent to get baseline thyroid function tests and quarterly monitoring for up-to 4 years on Alemtuzumab treatment given the high risk of developing thyroid dysfunction. Treatment of Graves disease remains the same in these patients with thionamides, iodine ablation or surgery.