Psychological well-being on thyroid hormone replacement

Despite 100 years after the discovery of thyroxine, controversy still exists regarding optimal thyroid hormone replacement therapy. Several anecdotal reports suggest that thyroxine alone therapy does not normalise psychological wellbeing. My cross-sectional study (n=1922) provided the first evidence in support of the hypothesis that a small proportion of patients on thyroxine alone therapy have increased psychological morbidity despite having normal TSH (publication 1). My second study was the largest randomised placebo controlled study to date to compare the effects of thyroxine alone and combined T3/T4 therapy over a 12 months period. This categorically proved that thyroxine alone therapy should be the first choice for hypothyroid patients (publication 2). Further genetic analysis of the deiodinase genes showed that a sub-group of hypothyroid patients with an SNP on D2 gene do have reduced psychological wellbeing on thyroxine alone therapy and improve on combined T3/T4 therapy compared to those without (publication 5). Both these findings were shown only by our study and were possible because of the large size (n=700). Detailed analysis of the various thyroid hormones and their ratio from our study showed that in addition to TSH, free T4 should be taken into account when treating hypothyroid patients (publication 4). My pharmacokinetic study provided the crucial and first evidence of the profiles of thyroid hormones on once a day combined T3/T4 therapy, highlighting the need to use either slow-release T3 or multiple doses of T3 in a day (publication 3). Our invited commentary and review (publications 6-8 & 10) have highlighted the importance of “individualised set points” for thyroid hormones, the complexity of thyroid hormone transport and actions as well as an algorithm for approaching hypothyroid patients. My other work (publication 9) was the first to test the possibility and provided the first evidence of deiodinase gene polymorphisms affecting circulating thyroid hormone levels and their possible role in psychological wellbeing in normal population. Thus, my work in the area, “Psychological wellbeing in patients of thyroid hormone replacement therapy” has provided several landmark findings, resulting in 10 publications including 4 in JCEM, 2 in Lancet and 1 in Clinical Endocrinology