SFEBES2016 ePoster Presentations (1) (116 abstracts)
Graves’ disease with fluctuating thyroid status and hypothyroidism with positive anti-TSH receptor antibody levels – distinctive autoimmune side-effects following alemtuzumab therapy for multiple sclerosis
Nadia Pariani 1 , Mark Willis 3 , Ilaria Muller 4 , Sarah Healy 3 , Taha Nasser 3 , Joanne Jones 2 , V. Krishna K. Chatterjee 1 , Colin Dayan 4 , Neil Robertson 3 , Alasdair Coles 2 & Carla Moran 1
1Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; 2Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 3Department of Neurology, University Hospital Wales, Cardiff, UK; 4Institute of Molecular & Experimental Medicine, Cardiff University, Cardiff, UK.
Alemtuzumab, a highly effective, newly-licensed, treatment for multiple sclerosis (MS), is notably associated with Graves’ disease (GD), which reportedly has an indolent course.
Methods: Case record review of patients who developed thyroid dysfunction (TD) after alemtuzumab treatment in Cambridge & Cardiff, to determine type, frequency and course of TD.
Results: 41.8% (104/249; 81F, 23M) of alemtuzumab-treated patients developed TD, mainly GD (69%). Mean age was 37.7 years. Mean TD onset was 23 months (range 2–107 months) post alemtuzumab; most (88.5%) occurred within 3 years of the last dose.
We focused further analysis on the 74 cases with follow up data (median 5 years; range 5–198 months) post TD. 52 (70%) of these developed GD; nine of whom (17%) showed fluctuating thyroid status (seven transitioning from hypo to hyperthyroidism and two vice versa). 29 GD patients completed a course of anti-thyroid drug (ATD) therapy, with 48% (14/29) relapsing and 52% (15/29) in remission after drug withdrawal; eight patients had definitive treatment before the end of course of medical treatment mainly because of difficult control of thyroid function on ATD treatment. Three cases of thyroiditis, seven cases of anti-TPO antibody positive hypothyroidism, two seronegative hypothyroidism were identified; in 10 cases, hypothyroidism with positive TRAB was recorded. Seven of 62 (11.3%) TRAb+ patients had signs of Graves’ ophthalmopathy (GO); two with severe GO.
Conclusion: Post-alemtuzumab TD occurred more frequently then previously described. GD was the most common cause of TD, with post therapy relapse rate not lower than conventional GD. Fluctuating thyroid status in alemtuzumab-induced GD (17% of cases), together with an unexpectedly high occurrence of TRAB+ hypothyroidism, suggests that both stimulating and blocking anti-TSH receptor antibodies develop in this context. We aim to investigate this hypothesis by checking the TRAb bioactivity in those patients with fluctuating thyroid status.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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