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dc.contributor.authorPariani, Nadia
dc.contributor.authorWillis, Mark
dc.contributor.authorMuller, Ilaria
dc.contributor.authorHealy, Sarah
dc.contributor.authorNasser, Taha
dc.contributor.authorMcGowan, Anne
dc.contributor.authorLyons, Greta
dc.contributor.authorJones, Joanna
dc.contributor.authorChatterjee, Krishna
dc.contributor.authorDayan, Colin
dc.contributor.authorRobertson, Neil
dc.contributor.authorColes, Alasdair
dc.contributor.authorMoran, Carla
dc.date.accessioned2018-10-10T17:31:11Z
dc.date.available2018-10-10T17:31:11Z
dc.date.issued2018-08-01
dc.identifier.issn0021-972X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283591
dc.description.abstractContext: 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 patients with MS in the United Kingdom. Design: Case records of alemtuzumab-treated patients who developed TD were reviewed. Results: A total of 41.1% (102 out of 248; 80 female and 22 male) of patients developed TD, principally GD (71.6%). Median onset was 17 months (range 2 to 107) following the last dose, with the majority (89%) within 3 years. Follow-up data (range 6 to 251 months) were available in 71 case subjects, of whom 52 (73.2%) developed GD: 10 of these (19.2%) had fluctuating TD. All 52 patients with GD commenced antithyroid drugs (ATDs): 3 required radioiodine (RAI) due to ATD side effects, and 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; and long-term ATDs, n = 8). Three cases of thyroiditis and 16 cases of hypothyroidism were documented: 5 with antithyroid peroxidase antibody positivity only, 10 with positive TSH receptor antibody (TRAb), and 1 of uncertain etiology. Bioassay confirmed both stimulating and blocking TRAb in a subset of fluctuating GD cases. Conclusions: Contrary to published literature, we recorded frequent occurrence of GD that required definitive or prolonged ATD 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.
dc.format.mediumPrint
dc.languageeng
dc.publisherThe Endocrine Society
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectMultiple Sclerosis
dc.subjectThyroid Diseases
dc.subjectThyroiditis
dc.subjectDisease Progression
dc.subjectRetrospective Studies
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectGraves Disease
dc.subjectMale
dc.subjectYoung Adult
dc.subjectAlemtuzumab
dc.titleAlemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features.
dc.typeArticle
prism.endingPage3018
prism.issueIdentifier8
prism.publicationDate2018
prism.publicationNameJ Clin Endocrinol Metab
prism.startingPage3010
prism.volume103
dc.identifier.doi10.17863/CAM.30953
dcterms.dateAccepted2018-06-01
rioxxterms.versionofrecord10.1210/jc.2018-00359
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08
dc.contributor.orcidJones, Joanna [0000-0003-4974-1371]
dc.contributor.orcidChatterjee, Krishna [0000-0002-2654-8854]
dc.contributor.orcidColes, Alasdair [0000-0003-4738-0760]
dc.identifier.eissn1945-7197
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMULTIPLE SCLEROSIS SOCIETY (39)
pubs.funder-project-idWellcome Trust (095564/Z/11/Z)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idWellcome Trust (105924/Z/14/Z)
pubs.funder-project-idWellcome Trust (105924/Z/14/A)
pubs.funder-project-idWellcome Trust (105924/Z/14/Z)
pubs.funder-project-idWellcome Trust (105924/Z/14/A)
pubs.funder-project-idMedical Research Council (G0502115)
pubs.funder-project-idMedical Research Council (G0600717)
pubs.funder-project-idMedical Research Council (G1100114)
cam.issuedOnline2018-06-06


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Except where otherwise noted, this item's licence is described as Attribution 4.0 International