wEight chanGes, caRdio-mEtabolic risks and morTality in patients with hyperthyroidism (EGRET): a protocol for a CPRD-HES linked cohort study

Barbara Torlinska, Jonathan M Hazlehurst, Krishnarajah Nirantharakumar, G Neil Thomas, Julia R Priestley, Samuel J Finnikin, Philip Saunders, Keith R Abrams, Kristien Boelaert

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INTRODUCTION: Hyperthyroidism is a common condition affecting up to 3% of the UK population. Treatment improves symptoms and reduces the risk of atrial fibrillation and stroke that contribute to increased mortality. The most common symptom is weight loss, which is reversed during treatment. However, the weight regain may be excessive, contributing to increased risk of obesity. Current treatment options include antithyroid drugs, radioiodine and thyroidectomy. Whether there are differences in either weight change or the long-term cardiometabolic risk between the three treatments is unclear.

METHODS AND ANALYSIS: The study will establish the natural history of weight change in hyperthyroidism, investigate the risk of obesity and risks of cardiometabolic conditions and death relative to the treatment. The data on patients diagnosed with hyperthyroidism between 1 January 1996 and 31 December 2015 will come from Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office of National Statistics Death Registry. The weight changes will be modelled using a flexible joint modelling, accounting for mortality. Obesity prevalence in the general population will be sourced from Health Survey for England and compared with the post-treatment prevalence of obesity in patients with hyperthyroidism. The incidence and time-to-event of major adverse cardiovascular events, other cardiometabolic outcomes and mortality will be compared between the treatments using the inverse propensity weighting model. Incidence rate ratios of outcomes will be modelled with Poisson regression. Time to event will be analysed using Cox proportional hazards model. A competing risks approach will be adopted to estimate comparative incidences to allow for the impact of mortality.

ETHICS AND DISSEMINATION: The study will bring new knowledge on the risk of developing obesity, cardiometabolic morbidity and mortality following treatment for hyperthyroidism to inform clinical practice and public health policies. The results will be disseminated via open-access peer-reviewed publications and directly to the patients and public groups (Independent Scientific Advisory Committee protocol approval #20_000185).

Original languageEnglish
Article numbere055219
Number of pages8
JournalBMJ open
Issue number10
Publication statusPublished - 1 Oct 2021

Bibliographical note

Funding Information:
Competing interests KRA has served as a paid consultant, providing unrelated methodological advice to Abbvie, Amaris, Allergan, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Meyers Squibb, Creativ-Ceutical, GSK, ICON/Oxford Outcomes, Ipsen, Janssen, Eli Lilly, Merck, NICE, Novartis, NovoNordisk, Pfizer, PRMA, Roche and Takeda, and has received research funding from the Association of the British Pharmaceutical Industry, European Federation of Pharmaceutical Industries & Associations, Pfizer and Sanofi. He is a partner and director of Visible Analytics Limited, a healthcare consultancy company.

Contributors BT, JMH, KN, GNT, KRA and KB participated in the study’s conception and initial design, with further substantial contributions from SJF, PS and JRP. All authors participated in drafting the protocol and approved the final version. Funding This project is funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit programme (grant number NIHR200772). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Publisher Copyright:
© 2021 Author(s) (or their employer(s)). Re-use permitted under CC BY. Published by BMJ.


  • cardiac epidemiology
  • epidemiology
  • thyroid disease

ASJC Scopus subject areas

  • Medicine(all)


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