Alemtuzumab-Induced Hypothyroidism Presenting in Pregnancy - the First 2 Reported Cases

Abstract

Abstract Introduction: Alemtuzumab is a monoclonal antibody that improves outcomes in patients with relapsing-remitting multiple sclerosis. It binds to CD52 and causes a profound depletion of B and T lymphocytes. Autoreactive T cells often form as the immune system repopulates, causing autoimmune thyroid dysfunction in approximately 35% of patients. Alemtuzumab has been associated with new-onset hyperthyroidism during a subsequent pregnancy. Here, we present the first two cases of alemtuzumab-induced hypothyroidism diagnosed in pregnancy. Diagnosing and treating de novo thyroid dysfunction in pregnancy is essential for optimal fetal development and maternal wellbeing. Clinical Cases: Case A: A 28-year-old woman conceived 26 months after alemtuzumab therapy. Prior to pregnancy, routine TFTs showed euthyroidism. At 17 weeks’ gestation she presented with fatigue, and blood tests confirmed overt hypothyroidism (TSH >100mIU/L (<4IU/L), fT4 3.7pmol/L (9-15pmol/L)). TRABs were positive. She was treated with levothyroxine, and TFTs normalised by 38 weeks’ gestation. Serial fetal ultrasounds showed constant growth velocity and no fetal goitre or tachycardia. The baby was born at term with birthweight on the 30th centile. On day 5 postpartum, the baby had a normal TSH of 3.1mIU/l (0.27-4.20mIU/l) but elevated fT4 of 31.5pmol/L (12-22pmol/L), which fell spontaneously to 22.0pmol/L by day 11. Case B: A 37-year-old woman conceived 19 months after alemtuzumab therapy. Prior to pregnancy, routine TFTs had been within normal limits. However at 5 weeks’ gestation, blood tests showed overt hypothyroidism (TSH 47.9mIU/L (<4iU/L)), fT4 8.8pmol/l (10-16pmol/L)). Her only symptom was fatigue. TRABs were elevated. She was treated with levothyroxine, and TFTs normalised by 16 weeks’ gestation. Serial fetal ultrasound scans showed constant growth velocity and no fetal goitre or tachycardia. The baby was born at term with birthweight on the 25th centile. On day 1 postpartum, the baby had a normal fT4 (16.5pmol/l)but elevated TSH 13.02mIU/L, which normalised spontaneously by day 11 tp 1/64mIU/l. Conclusion: To optimise pregnancy outcomes, we recommend that women previously treated with alemtuzumab should be screened monthly for thyroid dysfunction during a subsequent pregnancy. The neonatal team should be alert to transient neonatal thyroid dysfunction, which, like spontaneous alloimmune neonatal thyroid disease, appears to settle spontaneously.