8713 Fluctuating Graves' Disease: A Rare Complication of Alemtuzumab

Disclosure: B. Tran: None. D.A. Woodfield: None. D. Poudyal: None. P. Majety: None. Background: Alemtuzumab is a monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis. Its principal adverse effect is the development of autoimmunity. Thyroid autoimmunity is most common occurring in about 17% to 34%, with Graves’ disease (GD) comprising 60% to 70% of these cases. Alternating hypothyroidism and hyperthyroidism occur rarely in GD. Thyrotropin Receptor Binding Antibodies (TRAb) are functionally heterogeneous and can coexist in the same individual. They can be either stimulating, blocking, or neutral. Spontaneous switch between hypo- and hyperthyroidism, which can be bidirectional, occurs rarely and is thought to be due to a shift in the ratio between blocking and stimulating TRAbs. Clinical Case: A 42-year-old black woman with multiple sclerosis was treated with Alemtuzumab between 2019-2020, before which she was noted to have normal thyroid function tests. In 2022, she presented with hypothyroid symptoms and anterior neck pain with a Thyroid Stimulating Hormone (TSH) of 34.6 (0.35-4.94 uIU/mL) and elevated Thyroid-peroxidase (TPO) antibodies of 76 (0-34 IU/mL). She was started on levothyroxine 175 mcg. Over the next six months, her TSH gradually decreased and eventually became undetectable. Although the levothyroxine dose was gradually tapered, followed by complete cessation, she remained hyperthyroid, both clinically and biochemically. She had symptoms of palpitations, tremors, diaphoresis and a 20 lb weight loss. Additional workup was notable for elevated Thyroid-stimulating Immunoglobulin (TSI) at 19.3 (0-0.55 IU/L) and TRAb at 20 (0-1.75 IU/L). A radioactive iodine uptake scan showed increased and uniform tracer uptake of 72%, confirming GD. She was initially treated with methimazole (MMI) 20mg daily with rapid improvement. MMI was quickly tapered to 2.5mg daily within 2 months and while on this dose, her TSH rose to 58.2 necessitating cessation of MMI. Conclusion: This case illustrates the importance of continued monitoring for autoimmune thyroid complications, in patients receiving Alemtuzumab for multiple sclerosis, even after cessation of treatment. In patients presenting with hypothyroidism, both TPO and TRAb should be checked. Patients with TRAb-positive hypothyroidism should be closely monitored for potential fluctuation in disease course. Presentation: 6/1/2024