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Common variation in thyroid hormone status; effects on key health outcomes

Taylor, Peter ORCID: 2018. Common variation in thyroid hormone status; effects on key health outcomes. PhD Thesis, Cardiff University.
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Chronic pathological variation in thyroid function has major adverse outcomes on adult health, pregnancy and childhood development. However, it is less clear whether more minor variation, including variation across and just outside the reference-range has sufficient impact to justify intervention in selected individuals. Aims To investigate the relationship between modest variation in thyroid function on health outcomes, and how our treatment of hypothyroidism may relate to this, including screening for and treating low thyroid function in pregnancy. Scope I investigated the relationship between variation in thyroid function within the normal reference-range on health outcomes and identified that lower thyroid function was associated with adverse cardiovascular and metabolic outcomes and higher thyroid function was associated with adverse bone outcomes. I also identified in the ALSPAC cohort that TSH, FT3 and FT4 were all associated with body composition. However, FT3 was surprisingly positively associated with fat mass and genetic analyses indicated that higher fat mass was driving the higher FT3 levels. I then investigated current UK management of hypothyroidism utilising a large primary care database. Here I demonstrated a falling TSH threshold at levothyroxine initiation and a high risk of over-treatment. Individuals with depression or tiredness were more likely to be over-replaced. Women with suboptimal replacement during pregnancy had a higher risk of foetal loss. I then utilised data from the CATS trial and data linkage via SAIL to demonstrate that screening for and treating low thyroid function during pregnancy reduces foetal loss. Conclusion Common variation in thyroid status appears to be a modifiable risk factor for adverse health outcomes. Targeted treatment in patient sub-groups may provide substantial benefit. Furthermore, FT3 appears to be more fluid and influenced by external factors. Further research into novel methods of assessing tissue thyroid hormone levels may provide clarity to the treatment of borderline thyroid function.

Item Type: Thesis (PhD)
Date Type: Submission
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 17 September 2018
Last Modified: 08 Nov 2022 11:28

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