Title: Study of Optimal Replacement of Thyroxine in ElDerly (SORTED)- a feasibility study.
Funder: Department of Health (England)

Abstract: Background Hypothyroidism has a prevalence of up to 16% in elderly females and the number of individuals diagnosed with it is expected to rise due to increased life expectancy. Currently, all individuals with hypothyroidism are treated as a homogenous group, irrespective of age, to aim for serum TSH levels within the reference range. However, thyroxine metabolism is altered and bodily turnover is decreased in advanced age. Furthermore, ‘age-adjusted’ reference ranges are not employed. Moreover, mild hypothyroidism in the very elderly may have a protective influence on mobility and cardiovascular mortality compared to euthyroid or hyperthyroid individuals. Therefore, it is imperative to determine the optimal thyroid replacement strategy for the large number of older individuals with this problem. Aims The aim of this feasibility study is to furnish data to plan a large multicentre HTA-funded RCT of lower dose versus usual dose L-thyroxine (LT4) therapy in elderly hypothyroid individuals. The specific aims of the feasibility study are: 1. To determine the resources, tools and methodology required prior to performing a large RCT in elderly people with hypothyroidism 2. To study whether participating in the trial is acceptable to and well-tolerated by patients, and supported by their GPs 3. To explore the length of time needed to achieve full recruitment 4. To understand patients willingness to participate in the trial 5. To audit current practice of the management of hypothyroidism in elderly individuals. (Are all patients treated similarly, are there adverse effects or worse outcome?) Plan of Investigation Fifty individuals aged >=80 years currently being treated for primary hypothyroidism with LT4 in the community will be recruited from local primary care practices. Participants will be randomised in a single blinded manner to usual dose LT4 (target TSH level 0.4 – 4.0 mU/L) or lower dose LT4 (target TSH levels 4.1 – 8.0 mU/L). Post randomisation, individuals will be assessed at 12 weeks (and thyroxine dose adjusted) and finally at 24 weeks (close of study) with a final set of investigations including hypothyroid specific quality of life scores, mobility and serum cardiovascular risk markers. A qualitative study in a subgroup of participants will be undertaken. Morbidity and mortality of elderly treated hypothyroid individuals will be evaluated in a retrospective audit. Potential Impact If this feasibility study shows that elderly individuals with treated primary hypothyroidism will participate in a RCT of lower dose vs usual dose LT4 and if it confirms that patients participate and feel no worse on lower dose therapy, then an application for funding a full RCT will be made to the Health Technology Assessment (HTA) for the Clinical Evaluation and Trials funding stream. This will be designed with the specific aim to assess mortality, cardiovascular morbidity and quality of life. This research will add to the strength of accumulating evidence that normal population reference ranges for serum TSH and thyroid hormones need to be age-specific and could provide seminal data to change management of hypothyroidism in very elderly patients in the NHS and the wider world.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: METABOLIC AND ENDOCRINE