An overactive thyroid gland (hyperthyroidism) is common. Leaving the condition untreated can lead to serious health consequences as well as significant weight loss; however, treatment has been linked to additional weight gain, which is associated with increased risk of diabetes and heart disease.
The treatments for hyperthyroidism include surgery, radioiodine or medication. Recent studies showed significant differences in mortality between these treatments. However, not much is known about any other health risks.
Patients told us that weight gain and associated health risks were important issues as part of decision-making in which treatment to choose. They were disappointed that there was not much information available and that there was no ongoing research in that field. They felt strongly about the need to warn patients of potential risk of excessive weight gain, if such exists, and about the need to prevent the excess weight gain that many of them had experienced when they were treated.
The objective of this research is: (i) to investigate weight changes during treatment; (ii) to establish the risk of weight gain in each treatment; (iii) to compare the risk of developing diabetes, dementia, heart conditions or death in each treatment option. Currently, there is little information on this for UK patients.
Based on the results we aim to produce high quality information for doctors and patients about the risks of different treatment options to support more informed decision-making. If our study shows excessive weight gain following treatment for hyperthyroidism, we will develop a plan to prevent this.
The study aims to establish the natural history of weight changes in hyperthyroidism in any of the three treatment modalities, investigate the risk of obesity in regard to the treatment and compare these risks to the background population, and establish risks of cardio-metabolic conditions and death in each treatment modality. The data on patients diagnosed with hyperthyroidism between 01/04/1997 and 31/12/2015 will come from Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and ONS Death Registry.
The natural history of weight changes will be modelled longitudinally using a flexible joint modelling approach, accounting for mortality (wp1). BMI and obesity prevalence in the background population will be sourced from Health Survey England and compared with the post-treatment prevalence of obesity in patients with hyperthyroidism, stratified by sex with adjustment for age (wp2). Analyses of the incidence and time-to-event of major adverse cardiovascular events (MACE), other cardio-metabolic outcomes, diagnosis of dementia and mortality in each treatment modality will be compared using inverse weights of propensity score (wp3). Incidence rate ratios of outcomes will be modelled with Poisson regression adjusting for time-varying covariates. 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. Pairwise comparisons will be corrected for multiple testing by applying Bonferroni correction.
Our study will bring new knowledge on the risks of developing obesity following the treatment for hyperthyroidism and risks of developing cardio-metabolic morbidity and mortality. Our study has the unique potential to better inform treatment choice, a priority voiced by patients. The findings will also inform the future design of any interventional studies to prevent excessive weight gain and adverse cardio-metabolic outcomes following treatment for hyperthyroidism.
• Body weight changes over time;
• Prevalence of obesity;
• Incidence rate and time-to-event of:
Composite endpoint of major adverse cardiovascular events (MACE) defined as the occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke as per admission to hospital;
admission to hospital due to congestive heart failure;
admission to hospital due to ischaemic heart disease;
admission to hospital due to stroke and transient ischaemic attack (TIA);
either admission to hospital or diagnosis at GP of diabetes mellitus;
diagnosis of dementia
all-cause mortality as per ONS record.
Barbara Torlinska - Chief Investigator - University of Birmingham
Barbara Torlinska - Corresponding Applicant - University of Birmingham
Daniel Lasserson - Collaborator - University of Warwick
G. Neil Thomas - Collaborator - University of Birmingham
Jonathan Hazlehurst - Collaborator - University of Birmingham
Julia Priestley - Collaborator - British Thyroid Foundation
Keith Abrams - Collaborator - University of Leicester
Krishnarajah Nirantharakumar - Collaborator - University of Birmingham
Kristien Boelaert - Collaborator - University of Birmingham
Philip Saunders - Collaborator - NHS BIRMINGHAM AND SOLIHULL CCG
Samuel Finnikin - Collaborator - University of Birmingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation