Consequences of Over-Diagnosing Hypothyroidism in an Ageing United Kingdom population (CODHA UK)

Problem

Hypothyroidism is a common condition with approximately 3-5% of the UK population suffering. Most people diagnosed with hypothyroidism are prescribed thyroid hormone replacement, typically levothyroxine. The number of prescriptions for levothyroxine is increasing each year in the UK. Subclinical hypothyroidism is diagnosed when a patient has elevated thyroid-stimulating hormone levels. There is evidence for rising thyroid-stimulating hormone levels with age, but despite this age-specific reference ranges for diagnosing hypothyroidism are not used. Therefore, we may be over-prescribing elderly patients with levothyroxine, giving worse cardiovascular and bone health outcomes.The aim of this study is to compare the cardiovascular (diagnosis of angina, myocardial infarction, stroke, peripheral vascular disease, or stent/revascularisation procedure) and bone health (diagnosis of osteoporosis, fragility fractures, or minimal trauma fractures) outcomes between people treated with levothyroxine with mildly elevated thyroid-stimulating hormone levels compared to those not receiving levothyroxine despite mildly elevated thyroid-stimulating hormone levels.

Approach

There will be two studies conducted. Firstly, a retrospective cohort study using electronic patient records held in The Health Improvement Network database. Secondly, an emulated target trial study will be conducted using the same patient records. A systematic review has also been completed as part of the background for this study. Both the cohort study and emulated target trial study will analyse patients aged 50 years and over with a recorded thyroid-stimulating hormone level of at least 4.0mIU/l. Preliminary counts from The Health Improvement Network show that 280,525 patients in the database are aged over 50 with an elevated thyroid-stimulating hormone level between 2006 and 2021. Of those patients, 128,452 also have a hypothyroidism diagnosis.

Findings

Preliminary work conducted at a large rural general practice in Northumberland, England has shown an excess of patients prescribed levothyroxine without a diagnosis of hypothyroidism. A systematic review completed as background work found only 3 small-scaled studies on the topic, with a pooled odds ratio of 1.11 (95% confidence interval 0.84 – 1.45). This systematic review indicates that levothyroxine may be associated with detrimental bone health and cardiovascular outcomes in elderly subclinical hypothyroid patients, however, the pooled analysis on the limited studies available is inconclusive.

Consequences

The main outputs from this study will be reports (funder, local and national policy makers) and academic publications, as well national and international conference presentations. The findings of this study aim to influence policy to introduced age-specific reference ranges for thyroid-stimulating hormone levels. The results from this study will be presented in the 2023-24 academic year.