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Alemtuzumab-induced thyroid dysfunction exhibits distinctive clinical and immunological features

Pariani, Nadia, Willis, Mark, Muller, Ilaria, Healy, Sarah, Nasser, Taha, McGowan, Anne, Lyons, Greta, Jones, Joanne, Chatterjee, Krishna, Dayan, Colin, Robertson, Neil, Coles, Alasdair and Moran, Carla 2018. Alemtuzumab-induced thyroid dysfunction exhibits distinctive clinical and immunological features. Journal of Clinical Endocrinology & Metabolism 108 (8) , pp. 3010-3018. 10.1210/jc.2018-00359

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Abstract

Context Alemtuzumab, a highly effective treatment for multiple sclerosis (MS), predisposes to Graves’ disease (GD) with a reportedly indolent course. Objective To determine the type, frequency and course of thyroid dysfunction (TD) in a cohort of alemtuzumab-treated MS patients in the UK. Design Case records of alemtuzumab-treated patients who developed TD were reviewed. Results 41.1% (102/248; 80F, 22M) of patients developed TD, principally GD (71.6%). Median onset was 17 months (range 2-107) following last dose; the majority (89%) within 3 years. Follow-up data (range 6-251 months) was available in 71 cases, of whom 52 (73.2%) developed GD: 10 of these (19.2%) had fluctuating TD. All 52 GD patients commenced anti-thyroid drugs (ATD): 3 required radioiodine (RAI) due to ATD side-effects, drug therapy is ongoing in 2; of those who completed a course, 16 are in remission, 1 developed spontaneous hypothyroidism, and 30 (64%) required definitive or long-term treatment (RAI n=17, thyroidectomy n=5, long-term ATDs n=8). 3 cases of thyroiditis and 16 cases of hypothyroidism were documented; 5 with anti-TPO antibody positivity only, 10 with positive TRAb, 1 hypothyroidism (uncertain aetiology). Bioassay confirmed both stimulating and blocking TRAb in a subset of fluctuating GD cases. Conclusions Contrary to published literature, we have recorded frequent occurrence of GD that required definitive or prolonged antithyroid drug treatment. Furthermore, fluctuating thyroid status in GD and unexpectedly high frequency of TRAb-positive hypothyroidism suggested changing activity of TRAb in this clinical context; we have documented the existence of both blocking and stimulating TRAb in these patients.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: The Endocrine Society
ISSN: 0021-972X
Date of First Compliant Deposit: 13 June 2018
Date of Acceptance: 1 June 2018
Last Modified: 19 Oct 2019 20:07
URI: http://orca-mwe.cf.ac.uk/id/eprint/112233

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