Management of pregnancy in patients with Graves’ disease secondary to alemtuzumab: a case series and literature review

Introduction Alemtuzumab treatment for multiple sclerosis frequently induces Graves’ disease (GD), characterized by common coexistence of stimulating and blocking anti-thyrotropin receptor autoantibodies (TRAb), causing fluctuations of thyroid function. Alemtuzumab-induced TRAb-positive hypothyroidism is also common. These conditions are challenging to manage during pregnancy, considering the imperative necessity to maintain euthyroidism to minimize risks for both pregnancy and fetal/neonatal outcomes. Methods We reviewed the clinical course and therapeutic management of four pregnant women affected with alemtuzumab-induced GD or TRAb-positive hypothyroidism followed at our Institution, and seven additional cases published in literature. Results At our institution two patients with alemtuzumab-induced GD (one diagnosed before pregnancy, the other during the third trimester) showed a good control of thyroid function on anti-thyroid drugs (ATD). Two women had alemtuzumab-induced TRAb positive hypothyroidism; during pregnancy thyroid function was partially controlled with levothyroxine (LT4) alone in one case, and fully controlled with block and replace (ATD and LT4) in the other case. No pregnancy or fetal/neonatal negative outcomes were observed, except for preterm delivery of a healthy baby in Case 3, due to emergency cesarean section for pre-eclampsia progressing to HELLP syndrome. The literature search showed seven additional cases of pregnant women with alemtuzumab-induced GD (N = 5) or TRAb-positive hypothyroidism (N = 2), mainly diagnosed during gestation, especially in the first trimester. Six newborns developed transient thyroid dysfunction, often requiring treatment and later resolved. Conclusion The clinical management of alemtuzumab-induced thyroid dysfunction during pregnancy is challenged by frequent difficult maternal biochemical thyroid control and TRAb-mediated fetal/neonatal thyroid dysfunction. These patients need to be managed in a specialist setting, with close monitoring of maternal thyroid function and fetal/neonatal parameters, especially in cases with high TRAb titers.