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Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide

Lookup NU author(s): Dr Claire Wood, Mike Cole, Ruth Wood, Professor Simon PearceORCiD, Professor Timothy Cheetham



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2022 The authors Published by Bioscientifica Ltd.Objective: Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design: A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy. Methods: Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results: There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations. Conclusions: DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy.

Publication metadata

Author(s): Wood CL, Morrison N, Cole M, Donaldson M, Dunger DB, Wood R, Pearce SHS, Cheetham TD, Mayo A, Oxley C, Kirk J, Barrett T, Acerini C, Gregory J, Warner J, Stirling H, Greene S, Drake A, Shaikh G, Gault E-J, Staines J, Blair J, Dharmaraj P, Banerjee I, Ehtisham S, Johnstone H, Matthews D, Owen K, Thalange N, Dimitri P, Wright N, Wales J, Albanese A, Bain M

Publication type: Article

Publication status: Published

Journal: European Thyroid Journal

Year: 2022

Volume: 11

Issue: 1

Print publication date: 01/02/2022

Online publication date: 25/10/2021

Acceptance date: 25/10/2021

Date deposited: 09/02/2024

ISSN (print): 2235-0640

ISSN (electronic): 2235-0802

Publisher: BioScientifica Ltd.


DOI: 10.1530/ETJ-21-0043

PubMed id: 34981745


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Funder referenceFunder name
British Thyroid Foundation
Child Growth Foundation
Medical Research Council