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Randomised trial of block and replace vs dose titration thionamide in young people with thyrotoxicosis

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



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Objective: First-line treatment of thyrotoxicosis in young people is thionamide anti-thyroid drug (ATD) in a blocking dose with levothyroxine replacement (block and replace, BR) or in a smaller dose tailored to render the patient euthyroid (dose titration, DT). Our objective was to determine which regimen provides more stable biochemical control. Design: A multi-centre phase III, open-label randomised trial comparing BR with DT in patients aged 2-17 years with newly diagnosed thyrotoxicosis at 15 UK centres. Methods: Patients were randomised shortly after diagnosis and treated for 3 years. The primary outcome was the percentage of serum thyroid-stimulating hormone (TSH) levels in the reference range between 6 months and 3 years. Secondary outcomes included the proportion of Free thyroxine (FT4) levels in the reference range, adverse event frequency and 4 years outcome (remission/relapse). Results: Eighty-two patients were randomised, with details on clinical course in 81 (62 Female); 40 were allocated to BR (41 DT). Three withdrew with one ineligible. The mean percentage of serum TSH within reference range was 60.2% in BR and 63.8% in DT patients; adjusted difference 4.3%, 95% CI (-7.8 to 16.4); P = 0.48. Proportions for FT4 were 79.2% in BR and 85.7% in DT patients; adjusted difference 6.8%, (-0.2 to 15.6); P = 0.13. Three patients developed neutropenia - all on BR. 6 BR and 10 DT patients were in remission at 4y. Conclusion: This randomised trial has shown no evidence to suggest that BR, when managing the young patient with thyrotoxicosis, is associated with improved biochemical stability when compared to DT.

Publication metadata

Author(s): Wood CL, Cole M, Donaldson M, Dunger DB, Wood R, Morrison N, Matthews JNS, Pearce SHS, Cheetham TD

Publication type: Article

Publication status: Published

Journal: European Journal of Endocrinology

Year: 2020

Volume: 183

Issue: 6

Pages: 637-645

Online publication date: 01/12/2020

Acceptance date: 18/09/2020

Date deposited: 16/11/2020

ISSN (print): 0804-4643

ISSN (electronic): 1479-683X

Publisher: BioScientifica Ltd.


DOI: 10.1530/EJE-20-0617

PubMed id: 33107439


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