Neuropsychiatric outcomes, muscular function and exploration of metabolic pathways disrupted in subclinical thyroid dysfunction: a prospective evaluation and impact of treatment
Description: <p>Subclinical thyroid dysfunction (SCTD), defined as mild hypo- or hyperfunction of the thyroid, is affecting about 10% of the adults aged ≥65 years. SCTD is associated with multiple problems of the older age, including cardiovascular disease and fractures. In 2008, we formed the international Thyroid Studies Collaboration with the goal of clarifying the risks of SCTD. Furthermore, we also conducted a large randomized controlled trial (RCT) of thyroxine (thyroid hormone substitute) therapy among elderly with subclinical hypothyroidism to clarify the benefits of treatment. Current evidence suggests that SCTD has an important role in cognitive, emotional, and muscular function, but data are limited and the pathophysiological mechanisms remain unclear. </p><p>We now propose to expand our successful international Thyroid Studies Collaboration with existing individual data from 73’000 participants of 18 prospective cohorts in order to assess the association between SCTD and the risk of cognitive impairment, depressive symptoms, muscular function and falls. Second, we propose to investigate within our ongoing RCT of elderly participants with subclinical hypothyroidism (TRUST trial) the impact of thyroxine therapy on fatigue, depressive symptoms and muscular function. We will also use a state-of-the-art metabolomics platform to explore the changes in metabolic pathways in response to thyroxine treatment using metabolomics, a novel method in biomedical research that explores metabolic pathways. Third, we will summarize the whole existing scientific evidence on the effect of thyroxine therapy in subclinical hypothyroidism to inform future guidelines. </p><p>Our proposal will lead to a better understanding of SCTD and its risks and will elucidate the underlying pathophysiological mechanisms. Results will help clinicians accurately identify patients at increased neuropsychiatric risk and better define optimal thresholds for targeted thyroxine therapy to prevent these risks. </p>
Amount: CHF 904,000
Funding type: research
Funder scheme: Project funding
Start date: 2017-07-01
End date: 2021-06-30
Investigator: Rodondi, Nicolas
Institution: University of Berne – BE
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Funded outputs count: 42
Funder award ID: 172676
OpenAlex ID: G517517375