Endocrine Abstracts

A 29 year old woman with multiple sclerosis and no history of thyroid dysfunction was referred to endocrinology with T3 thyrotoxicosis (TSH <0.01 mU/l, fT4 20.7 pmol/l, T3 2.9 nmol/l). She had received monoclonal alemtuzumab therapy 9 months prior. This hyperthyroid phase was short lived and in the absence of anti-thyroid medication developed symptomatic hypothyroidism within 2 months of referral (TSH 52.9 mU/l, T4 <5 pmol/l, T3 0.8 nmol/l). Thyroid receptor antibodies were raised (34 U/l) although thyroid peroxidase antibodies were within normal reference ranges (4.4 U/ml). Levothyroxine 100 mcg/day was initiated, but was downtitrated due to rising fT4 levels over the subsequent 6 months. Following the eventual discontinuation of levothyroxine, the patient was admitted acutely with symptomatic thyrotoxicosis (TSH <0.01 mU/l, fT4 34.9 pmol/l, T3 >9.2 nmol/l) with tachycardia (HR 160), anxiety, tremor and weight loss (>10 kg). High dose carbimazole therapy (60 mg/day) was initiated and the patient currently awaits radioactive iodine therapy for definitive treatment. Alemtuzumab is a humanised anti-CD52⁺ IgG1 monoclonal antibody utilised in the treatment of relapsing-remitting multiple sclerosis. It acts by targeting the CD52⁺ epitope on CD4⁺ and CD8⁺ T lymphocytes and B-cells, which results in their antibody- and complement-mediated depletion, subsequent repopulation and immune reconstitution. Up to one third of individuals receiving alemtuzumab experience thyroid dysfunction where fluctuations in thyroid activity are mediated via the coexistence and balance of thyroid receptor antibodies with stimulating and blocking functions. We report the case of a patient with relapsing-remitting multiple sclerosis who presented with three distinct phases of thyroid dysfunction following alemtuzumab. Surveillance of thyroid function is imperative in individuals receiving this therapy, and clinicians should be aware that thyroid dysfunction may alternate rapidly between hyperthyroid, euthyroid and hypothyroid states and severity.