1. Applying for EU FP7 research funding
David J Stott
David Cargill Professor of Geriatric Medicine

3. Summer 2010

4. Sabbatical, Leiden; Jan-March 2011

6. TRUST
Multi-modal effects of Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism; a randomised placebo-controlled Trial
THEME [HEALTH ] Investigator-driven clinical trials for therapeutic interventions in elderly populations

9. Definition – subclinical hypothyroidism
Few / no symptoms or signs of thyroid dysfunction
TSH > 4.5 IU/L
Serum free thyroxine (fT4) within the reference range
Excludes patients on T4 hormone treatment
Consensus conference
Surks, JAMA 2004;291:228

10. Prevalence of elevated TSH by age and gender
Canaris et al ,
The Colorado Thyroid Disease Prevalence Study, Arch Intern Med
2000;160:

11. Brain Heart Vascular system Bone Muscle Executive function
Verbal memory
Heart
Cardiac output
Atrial fibrillation
Vascular system
Cholesterol
Bone
Muscle

12. Subclinical Hypothyroidism and Coronary Heart Disease Mortality
Systematic review and meta-analysis
Prospective cohort studies
55,287 subjects, 6.2% subclinical hypothyroidism
HRs for CHD mortality
TSH mIU/L, HR 1.09 (95% CI, )
TSH mIU/L, HR 1.42 (95% CI, )
TSH mIU/L, HR 1.58 (95% CI, )
P=0.005 for trend
Similar results for CHD events
No association total mortality
Rodondi et al, JAMA. 2010;304:

13. Hypothyroidism in the Leiden 85+ study
No association with poor health status
disability, depression, cognitive impairment
Increased TSH and lower fT4 associated with lower mortality
HR 0.77 (95% CI ; P=0.009) per SD increase of TSH
HR 1.16 (95% CI, ; P=0.009) per SD increase of fT4
Gussekloo et al, JAMA, 2004;292:2591

14. Thyroid hormone replacement for subclinical hypothyroidism
Cochrane Database of Systematic Reviews
12 controlled trials, 6-14 months duration, 350 patients
Levo-thyroxine replacement versus placebo / no treatment
No data on (cardiovascular) mortality or morbidity
No significant improvement in symptoms, mood, QOL
Inconsistent effects on cognitive function
Probable reduction in total cholesterol
Improved LV diastolic function (echo)
Only 4 studies reported adverse events with no statistically significant differences between groups
Villar et al, CDSR, 2009

15. Balancing act – benefits and risks

16. Acknowledgements Funders EU FP7 Wellcome Trust CSO Scottish Executive
Collaborators
Ian Ford
Naveed Sattar
Gordon Lowe
Michele Robertson
Ann Rumley
Paul Welsh
Christopher J Packard
James Shepherd
Stuart Cobbe
Stella Trompet
Rudi Westendorp
Anton de Craen
J Wouter Jukema
Brendan Buckley
Patricia Kearney
Nicolas Rodondi
Funders
EU FP7
Wellcome Trust
CSO Scottish Executive
Bristol-Myers Squibb
Chest Heart and Stroke Scotland