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dc.contributor.authorAbbara, Ali
dc.contributor.authorClarke, Sophie
dc.contributor.authorBrewster, Rosalind
dc.contributor.authorSimmonard, Alexia
dc.contributor.authorEng, Pei Chia
dc.contributor.authorPhylactou, Maria
dc.contributor.authorPapadopoulou, Deborah
dc.contributor.authorIzzi-Engbeaya, Chioma
dc.contributor.authorSam, Amir
dc.contributor.authorJonauskyte, Eliza
dc.contributor.authorComninos, Alexander
dc.contributor.authorMeeran, Karim
dc.contributor.authorKelsey, Tom
dc.contributor.authorDhillo, Waljit
dc.identifier.citationAbbara , A , Clarke , S , Brewster , R , Simmonard , A , Eng , P C , Phylactou , M , Papadopoulou , D , Izzi-Engbeaya , C , Sam , A , Jonauskyte , E , Comninos , A , Meeran , K , Kelsey , T & Dhillo , W 2020 , ' Pharmacodynamic response to anti-thyroid drugs in Graves’ hyperthyroidism ' , Frontiers in Endocrinology , vol. 11 , 286 .
dc.identifier.otherPURE: 267500867
dc.identifier.otherPURE UUID: 1c312a58-4762-48dc-a79e-3acb45ffad72
dc.identifier.otherORCID: /0000-0002-8091-1458/work/74117899
dc.identifier.otherWOS: 000537287700001
dc.identifier.otherScopus: 85085382439
dc.descriptionThe Section of Endocrinology and Investigative Medicine was funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EuroCHIP grant and was supported by the NIHR Biomedical Research Centre Funding Scheme. AA was supported by an NIHR Clinician Scientist award. SC was supported by an NIHR Clinical Lectureship. AC was supported by the NHS and BRC. WD was supported by an NIHR Research Professorship (RP-2014-05-001).en
dc.description.abstractObjective: Graves' disease is the commonest cause of hyperthyroidism in populations with sufficient dietary iodine intake. Anti-thyroid drugs (ATD) are often used as the initial treatment for Graves' hyperthyroidism, however there is a paucity of data relating the dose of ATD therapy to the effect on thyroid hormone levels, increasing the risk of both over- and under-treatment. We aimed to determine the pharmacodynamic response to the ATD carbimazole. Design: Retrospective cohort study. Methods: Participants were patients (n = 441) diagnosed with Graves' disease at Imperial College Healthcare NHS Trust between 2009 and 2018. The main outcome measure was change in thyroid hormone levels in response to ATD. Results: Baseline thyroid hormone levels were positively associated with TSH receptor antibody titres (P < 0.0001). Baseline free triiodothyronine (fT3) were linearly related to free thyroxine (fT4) levels in the hyperthyroid state (fT3 = fT4*0.97–11), and fell proportionately with carbimazole. The percentage falls in fT4 and fT3 per day were associated with carbimazole dose (P < 0.0001). The magnitude of fall in thyroid hormones after the same dose of carbimazole was lower during follow up than at the initiation visit. The fall in thyroid hormone levels approximated to a linear response if assessed at least 3 weeks after commencement of carbimazole. Following withdrawal of antithyroid drug treatment, the risk of relapse was greater in patients with higher initial fT4, initial TSH receptor antibody titre, males, smokers, and British Caucasian ethnicity. Conclusion: We identify a dose-response relationship for fall in thyroid hormones in response to carbimazole to aid in the selection of dose for Graves' hyperthyroidism.
dc.relation.ispartofFrontiers in Endocrinologyen
dc.rightsCopyright © 2020 Abbara, Clarke, Brewster, Simonnard, Eng, Phylactou, Papadopoulou, Izzi-Engbeaya, Sam, Wernig, Jonauskyte, Comninos, Meeran, Kelsey and Dhillo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectGraves‘ diseaseen
dc.subjectAnti-thyroid drug (ATD)en
dc.subjectAnti-thyroid drug therapyen
dc.subjectRC Internal medicineen
dc.subjectRM Therapeutics. Pharmacologyen
dc.titlePharmacodynamic response to anti-thyroid drugs in Graves’ hyperthyroidismen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Computer Scienceen
dc.contributor.institutionUniversity of St Andrews.Centre for Interdisciplinary Research in Computational Algebraen
dc.description.statusPeer revieweden

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