Weight changes, cardio-metabolic risks and mortality in patients with hyperthyroidism; all-cohort natural history and comparison of treatment effects in a CPRD-HES linked study

Hyperthyroidism is a common condition that affects 3% of women and 0.3% of men in the UK adult population. Most common symptoms include weight loss, heat intolerance, tremor and palpitations.

Treatment to achieve euthyroid status improves symptoms and reduces the risk of atrial fibrillation and stroke that contribute to the increased mortality risk in hyperthyroidism. Current treatment options include: antithyroid drugs (ATDs), radioactive iodine (I-131 radioiodine) and thyroidectomy.

Weight gain during treatment is commonly seen, though it is unclear whether this simply represents regain of previously lost weight.

Whether there are differences in either weight change or the long-term cardio-metabolic risk between the three treatments is unclear. The absence of this information limits fully informed patient treatment choice.

The aim of this project is to investigate the risks of developing obesity, of developing cardio-metabolic conditions and of death in a large cohort of patients with hyperthyroidism and to compare the risks of these outcomes between all three modalities used to treat hyperthyroidism.

We propose to investigate the data collected in primary care pre- and post-diagnosis as a retrospective cohort study using Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and Office of National Statistics (ONS) Death Registry.

CPRD includes records from over 1,100 primary care practices within the UK including data from 35 million patients of whom 10 million are currently registered. CPRD is well-validated for epidemiological research across a range of health outcomes.

We will include patients with newly diagnosed hyperthyroidism in primary care between 1st January 1996 and 31st December 2015, allowing for a minimum of 4-years follow-up.

The diagnosis will be identified based on the appropriate Read codes; treatment administered will be based on the appropriate code: British National Formulary, Read system, the Office of Population Censuses and Surveys Classification of Interventions and Procedures (OPCS-4), or International Classification of Diseases.

From feasibility searches, we anticipate identifying 25,000 patients with newly diagnosed hyperthyroidism eligible for HES linkage whose data meet acceptable quality record criteria.

Our study will consist of three work packages: (1) modelling natural history of weight change during the course of hyperthyroidism treatment; (2) comparing post-treatment prevalence of obesity in the hyperthyroid cohort with the background population (Health Survey England); (3) analysing incidence of cardiovascular, metabolic and mortality outcomes between the three treatment arms.

Deeming real-life clinical trial not feasible, we are proposing analytical approaches emulating a clinical trial using routinely collected data.

We anticipate the results of our study to bring new knowledge on risks of becoming obese following the treatment for hyperthyroidism as well as risks of developing cardio-metabolic morbidity and mortality.

Our study has the unique potential to better inform treatment choice, a priority voiced by patients in during our Patients and Public Engagement meeting.

The findings from this study will also inform future design of any interventional studies to prevent excessive weight gain and adverse cardio-metabolic outcomes following treatment for hyperthyroidism.