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Is there a difference in mortality and cardiovascular disease in patients with subclinical hypothyroidism who are treated with levothyroxine compared to those who are not treated?


School of Medicine

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Prof C McCowan , Dr A Azcoaga-Lorenzo , Dr Utkarsh Agrawal Agrawal No more applications being accepted Funded PhD Project (Students Worldwide)

About the Project

Subclinical hypothyroidism (SCH) is a biochemical state where thyrotropin TSH is elevated above the reference range but free thyroxine (T4) levels are within the reference range. It is often detected incidentally, although some people may experience symptoms. The reported prevalence of subclinical hypothyroidism varies significantly between 3% up to 15 % with a higher incidence associated with increasing age and female sex. Few clinical trials have found that treatment do not provide apparent benefits in terms of improving symptoms or quality of life in the short term. However, there is not robust evidence on how treatment affect long term outcomes. Observational studies involving patients with subclinical hypothyroidism have shown lower risk of cardiovascular events, frailty fractures and death among patients who received levothyroxine than among patients who did not receive levothyroxine. However, data on the associations with these long-term outcomes are conflicting among different large prospective cohorts and data from randomised controlled trials to inform the effects of treatment of subclinical hypothyroidism are lacking. This conflicting findings and different interpretations of the existing evidence translate into variable recommendations from clinical guidelines. Only in the last 12 months The BMJ has published two guidelines on subclinical hypothyroidism whose recommendations differ. Moreover, despite population-based screening of asymptomatic adults for thyroid disorders is not recommended, as there is no evidence that this is beneficial, is one of the most demanded tests by GPs and there are concerns about overuse and the cost that this implies. As the number of people tested is high it is expected that significant number of patients will be continue being diagnosed with SCH. This study will benefit patients by increasing the evidence on the appropriate clinical management of this condition but also has the potentiality to inform doctors on the indications for testing which will contribute to a better use of resources.

Research objective

To compare the risks of cardiovascular events and total mortality for adults with subclinical hypothyroidism among patients who received levothyroxine and among patients who did not receive levothyroxine.
Proposed methods
We propose to perform a clinical trial emulation. Although only adequately powered randomized controlled intervention trials would be able to demonstrate whether treatment of SCH is worthwhile in terms of improvement in both, cardiovascular disease risk and mortality, such a trial has not been performed to date and due to the long follow up period that would be needed it might never happen. Observational analyses of big databases might not the preferred choice for comparative effectiveness research however, using the adequate methods it’s possible to answer causal questions when the trial is not feasible.

Entry requirements
The candidate should possess skills in research methods, communication and scientific writing as well as the ability to work and learn from colleagues based in multiple disciplines. The candidate should have an interest and enthusiasm for the topic and methods of the studentship. Applicants for this project must have an Undergraduate degree (1st class Honours or 2:1) or Masters degree, or equivalent, in a relevant discipline e.g. public health, epidemiology, computer science, statistics or other numerate subjects.

The successful candidate will join a multidisciplinary health data science team and will gain skills and experience in systematic evidence synthesis, epidemiology, secondary data analysis, health data science, statistics and written and verbal communication skills.


Start date
As soon as possible.

For further details on the project or informal enquiries please contact Professor Colin McCowan on
[Email Address Removed]

How to apply

Applications should be submitted via the University application system at https://www.st-andrews.ac.uk/study/apply/postgraduate/research/


Closing date
Friday 28th August

Funding Notes

This is a 3 year funded PhD studentships comprising of tuition fees at Home/EU rate and stipend at current UKRI rates.


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