Claire L Wood1,2, Michael Cole3, Malcolm Donaldson4, David B Dunger5,6, Ruth Wood7, Niamh Morrison1, John N S Matthews8,8, Simon H S Pearce2,9, Timothy D Cheetham1,2. 1. Department of Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK. 2. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK. 3. Population Health Sciences Institute, Newcastle University, Baddiley-Clark Building, Newcastle upon Tyne, UK. 4. Department of Child Health, University of Glasgow School of Medicine, Glasgow, UK. 5. Department of Paediatrics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK. 6. Wellcome Trust-MRC Institute of Metabolic Sciences, University of Cambridge, Cambridge, UK. 7. Newcastle Clinical Trials Unit, Statistics & Physics, Newcastle University, Newcastle-upon-Tyne, UK. 8. School of Mathematics, Statistics & Physics, Newcastle University, Newcastle-upon-Tyne, UK. 9. Department of Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
Abstract
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.
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.
Authors: Tim D Cheetham; Michael Cole; Mario Abinun; Amit Allahabadia; Tim Barratt; Justin H Davies; Paul Dimitri; Amanda Drake; Zainaba Mohamed; Robert D Murray; Caroline A Steele; Nicola Zammitt; Sonya Carnell; Jonathan Prichard; Gillian Watson; Sophie Hambleton; John N S Matthews; Simon H S Pearce Journal: J Clin Endocrinol Metab Date: 2022-02-17 Impact factor: 5.958
Authors: Claire L Wood; Niamh Morrison; Michael Cole; Malcolm Donaldson; David B Dunger; Ruth Wood; Simon H S Pearce; Timothy D Cheetham Journal: Eur Thyroid J Date: 2022-01-01
Authors: Christiaan F Mooij; Timothy D Cheetham; Frederik A Verburg; Anja Eckstein; Simon H Pearce; Juliane Léger; A S Paul van Trotsenburg Journal: Eur Thyroid J Date: 2022-01-01