Translational studies towards understanding clinical effects of thyroid hormone

Despite adequate restoration of biochemical euthyroidism with replacement therapy with levothyroxine, a substantial amount of patients (~10-15%) with hypothyroidism display significant impairment of psychological well-being compared to controls of similar age and sex and show decrements in health status. The reasons for these observations are still unknown. The general focus of this thesis is therefore to explore the cause of persisting symptoms in treated hypothyroid patients and to find new biomarkers for thyroid state.
Health-related QoL was impaired in 143 athyreotic patients with differentiated thyroid cancer on levothyroxine replacement therapy compared with a Dutch reference group. However, we did not find any association between thyroid function tests and QoL within our study group.
We studied if microRNAs in serum are regulated by thyroid state in 13 patients with differentiated thyroid cancer off and on levothyroxine. The expression of 384 microRNAs was assessed with a TaqMan MicroRNA Array. The generated selected serum miRNA profile did not reveal new biomarkers for thyroid state.
Next generation RNA sequencing was performed in whole blood samples in a cohort of 8 patients on and off LT4 treatment. We demonstrated that numerous genes are regulated in different thyroid states. We also found that thyroid hormone affects gene expression in platelets, which might explain the reported increased risk of thrombosis in patients with hyperthyroidism.