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

Wood, C. L., Morrison, N., Cole, M., Donaldson, M., Dunger, D. B., Wood, R., Pearce, S. H.S. and Cheetham, T. D. (2022) Initial response of young people with thyrotoxicosis to block and replace or dose titration thionamide. European Thyroid Journal, 11(1), e210043. (doi: 10.1530/etj-21-0043) (PMID:34981745) (PMCID:PMC9142802)

Abstract

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.

• Item Type: Articles
• Additional Information: Funding: This trial was funded by both the British Thyroid Foundation and by the Child Growth Foundation. C W was funded by the Medical Research Council/MDUK (MR/N020588/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Donaldson, Dr Malcolm
• Authors: Wood, C. L., Morrison, N., Cole, M., Donaldson, M., Dunger, D. B., Wood, R., Pearce, S. H.S., and Cheetham, T. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: European Thyroid Journal
• Publisher: Bioscientifica
• ISSN: 2235-0640
• ISSN (Online): 2235-0802
• Published Online: 01 January 2022
• Copyright Holders: Copyright © The authors 2022
• First Published: First published in European Thyroid Journal 11(1):e210043
• Publisher Policy: Reproduced under a Creative Commons Licence