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Factors that influence the control of hypothyroidism and potential excess mortality associated with over-diagnosis in the elderly population.

School of Medicine

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Prof S Wilkes , Dr R Dew No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

PhD – 3 years full-time
NIHR Applied Research Collaboration North East and North Cumbria.
Theme 1: Multimorbidity, ageing and frailty.
Number of awards: 1
Start date and duration: 1st February 2021. The funding covers a three year PhD.

You will join a vibrant and growing research team in the new School of Medicine at the University of Sunderland.

Hypothyroidism is a common disease affecting 3-5% of the population and is the result of insufficient production of thyroid hormones. Over 99% of hypothyroid cases are caused by primary hypothyroidism or inadequate function of the thyroid gland and the majority of these are managed within the primary care setting. There are two vexing questions that challenge doctors and patients alike, firstly factors that influence/interfere with good thyroid control and secondly potential over-diagnosis in our ageing population, both of which can have adverse effects upon cardiovascular morbidity/mortality and bone health.

There is now a growing body of evidence describing the effects of a variety of factors on thyroid hormone therapy. Some of these factors include body weight, pregnancy, co-morbid conditions, consistency and quality of levothyroxine, drug interactions and dose timings, and behavioural factors such as adherence rates. Pharmacokinetic factors also play a role since levothyroxine is absorbed from the stomach and small bowel and its optimal absorption is dependent on the acidic environment of the stomach. Several factors are known to perturb absorption through this mechanism, including the use of calcium or iron salts, proton pump inhibitors, atrophic gastritis (pernicious anaemia) and coeliac disease. Pharmacogenomic associations may also be relevant to the adequacy of thyroxine therapy and the evidence in this area is increasing. For example within the metabolic pathway of thyroxine, polymorphisms in type 2 deiodinase, DIO2, (Thr92Ala) has been shown to influence the levothyroxine dose required to achieve target TSH levels.

Thus there are undoubtedly multifactorial reasons for poor response to therapy in patients with hypothyroidism. The review aims to summarise the contemporary literature and quantify the extent that clinical, behavioural and pharmacogenomic factors affect the response to levothyroxine and contribute to abnormal TSH levels in patients with primary hypothyroidism.

The second issue is that despite evidence for rising Thyroid Stimulating Hormone (TSH) levels with age, age-specific reference ranges for diagnosing hypothyroidism are not used because the evidence is not strong enough, and we may be over-treating elderly patients giving worse cardiovascular and bone health outcomes.

A retrospective cohort study that will use electronic patient records to determine any excess morbidity/mortality associated with age-related diagnostic thresholds. The primary outcome of this study is to compare the cardiovascular outcome between patients aged >50 years with mildly elevated TSH treated with LT4 versus those untreated. Secondary outcomes are bone health outcomes. Descriptive and inferential statistics will be used.

Findings may inform changes in treatment guidelines to improve cardiovascular outcomes (diagnosis of angina, myocardial infarction, stroke, peripheral vascular disease, stent/revascularisation procedure and cardiovascular death) in the elderly with a mildly elevated TSH.

Professor Scott Wilkes and Dr Rosie Dew, School of Medicine. Your extended supervisory team are leading academics from within the UK.

Eligibility Criteria:
The candidate should have a first degree (minimum 2:1) and Master’s degree in a related biomedical discipline, a strong desire to work in the subject area using large datasets and computational methods. A willingness to interact with people from many specialities, including biologists, clinicians, computer scientists and statisticians. Keenness to present their research findings at national and international meetings.

Some background in the following areas would be an advantage, but is not necessary, as attaining a level of fluency in these areas is expected over the course of the PhD:
- Database searching
- Academic writing and publication
- Statistics and knowledge of statistical analysis
- Knowledge of epidemiology

The award is available to UK/EU applicants only.

How to apply:
Applicants should send a copy of their CV and covering letter to Professor Scott Wilkes ([Email Address Removed]).
Closing date for applications: 22nd November 2020.

For further details regarding this exciting venture and opportunity, please contact Professor Scott Wilkes, Head of School of Medicine at [Email Address Removed].

Funding Notes

100% of UK/EU tuition fees paid, jointly funded by the University of Sunderland and The National Institute for Health Research Applied Research Collaborative North East and North Cumbria (NIHR ARC NENC), research consumables and annual living expenses stipend of £15,000 for each of the 3 years.

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