Lessons from Randomised Clinical Trials for Triiodothyronine Treatment of Hypothyroidism: Have They Achieved Their Objectives?

Journal of Thyroid Research
Rudolf HoermannJohannes W Dietrich

Abstract

Randomised controlled trials are deemed to be the strongest class of evidence in evidence-based medicine. Failure of trials to prove superiority of T3/T4 combination therapy over standard LT4 monotherapy has greatly influenced guidelines, while not resolving the ongoing debate. Novel studies have recently produced more evidence from the examination of homeostatic equilibria in humans and experimental treatment protocols in animals. This has exacerbated a serious disagreement with evidence from the clinical trials. We contrasted the weight of statistical evidence against strong physiological counterarguments. Revisiting this controversy, we identify areas of improvement for trial design related to validation and sensitivity of QoL instruments, patient selection, statistical power, collider stratification bias, and response heterogeneity to treatment. Given the high individuality expressed by thyroid hormones, their interrelationships, and shifted comfort zones, the response to LT4 treatment produces a statistical amalgamation bias (Simpson's paradox), which has a key influence on interpretation. In addition to drug efficacy, as tested by RCTs, efficiency in clinical practice and safety profiles requires reevaluation. Accordingly...Continue Reading

References

May 4, 2006·The Journal of Clinical Endocrinology and Metabolism·Simona Grozinsky-GlasbergLeonard Leibovici
Sep 26, 2008·Endocrine Reviews·Balázs GerebenAntonio C Bianco
Mar 18, 2009·Nursing Research·Suzanne AmeringerSandra Ward
Jul 7, 2009·Annual Review of Psychology·Patrick J Curran, Daniel J Bauer
Mar 20, 2010·European Journal of Endocrinology·Rudolf HoermannRolf Larisch
Oct 1, 2010·Endocrine Reviews·S PiehlJ Köhrle
Nov 28, 2012·European Journal of Endocrinology·Rudolf HoermannJohannes W Dietrich
Jan 24, 2013·Thyroid : Official Journal of the American Thyroid Association·Greet L RoefErnst R Rietzschel
Mar 30, 2013·The Journal of Clinical Endocrinology and Metabolism·Thanh D HoangMohamed K M Shakir
Aug 27, 2013·Current Opinion in Endocrinology, Diabetes, and Obesity·Leonard Wartofsky
Sep 17, 2013·Circulation. Arrhythmia and Electrophysiology·Youhua ZhangA Martin Gerdes
Jan 5, 2014·Clinical and Translational Gastroenterology·Amit G SingalAkbar K Waljee
Jan 18, 2014·Endocrine Reviews·Bernadette Biondi, Leonard Wartofsky
Jul 1, 2012·European Thyroid Journal·Wilmar M WiersingaMark P J Vanderpump
Jul 9, 2014·The Journal of Clinical Endocrinology and Metabolism·Torquil WattMogens Groenvold
Oct 1, 2014·Thyroid : Official Journal of the American Thyroid Association·Jacqueline JonklaasUNKNOWN American Thyroid Association Task Force on Thyroid Hormone Replacement
Jan 3, 2015·The Journal of Clinical Investigation·Joao Pedro Werneck de CastroAntonio C Bianco
Jan 9, 2015·The Journal of Clinical Endocrinology and Metabolism·Elizabeth A McAninchAntonio C Bianco
Mar 10, 2015·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·R HoermannJ W Dietrich
May 27, 2015·Clinical Endocrinology·Onyebuchi OkosiemeMark Vanderpump
Jul 15, 2015·European Journal of Endocrinology·Nienke Kelderman-BolkArie Berghout
Aug 12, 2015·The Journal of Clinical Endocrinology and Metabolism·Layal ChakerOscar H Franco
Sep 13, 2015·The Lancet. Diabetes & Endocrinology·Elizabeth A McAninch, Antonio C Bianco
Nov 8, 2015·World Journal of Surgery·Megan K ApplewhiteBriseis Aschebrook-Kilfoy
Dec 17, 2015·Journal of the American College of Cardiology·Stuart J PocockTim J Collier
Mar 5, 2016·Clinical Endocrinology·Graham P LeeseLouise A Donnelly
Apr 1, 2016·Thyroid : Official Journal of the American Thyroid Association·Jacqueline Jonklaas, Kenneth D Burman
May 4, 2016·Expert Review of Clinical Pharmacology·Jacqueline Jonklaas
Jul 5, 2016·Frontiers in Endocrinology·Johannes W DietrichRudolf Hoermann
Nov 23, 2016·Frontiers in Endocrinology·Rudolf HoermannJohannes W Dietrich
Jan 7, 2017·Thyroid : Official Journal of the American Thyroid Association·Mitsuru ItoNobuyuki Amino
May 6, 2017·Thyroid : Official Journal of the American Thyroid Association·Christel HedmanCatharina Ihre Lundgren
Jun 21, 2017·Current Opinion in Endocrinology, Diabetes, and Obesity·Jacqueline Jonklaas
Sep 1, 2017·European Journal of Endocrinology·Wilmar M Wiersinga
Oct 19, 2017·Frontiers in Endocrinology·Ramkumarie BaliramTerry F Davies
Oct 25, 2017·Circulation·Christine BaumgartnerUNKNOWN Thyroid Studies Collaboration
Nov 21, 2017·PloS One·Rudolf HoermannJohannes Wolfgang Christian Dietrich
Jan 30, 2018·Frontiers in Endocrinology·Rudolf HoermannJohannes W Dietrich
Feb 6, 2018·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Rolf LarischRudolf Hoermann
Feb 27, 2018·Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing·Shao-Bin WeiChang-Sheng Ma

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Citations

Oct 17, 2019·Frontiers in Endocrinology·Rudolf HoermannJohannes W Dietrich
May 16, 2019·Thyroid : Official Journal of the American Thyroid Association·Elena IzkhakovLital Keinan-Boker
Oct 17, 2019·Endocrine·Wilmar M Wiersinga
May 29, 2021·Klinicheskaia laboratornaia diagnostika·I A TsanavaA V Melikova
Sep 24, 2021·Current Medical Research and Opinion·Ulrike Gottwald-Hostalek, George J Kahaly
Aug 4, 2021·Thyroid : Official Journal of the American Thyroid Association·Juan Manuel Millan-AlanisRené Rodríguez-Gutiérrez
Dec 11, 2021·Frontiers in Cardiovascular Medicine·Assem AweimerJohannes W Dietrich

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