Endocrine Abstracts

Background: Numerous observational studies suggested that variation in thyroid function parameters even within the normal range associates with adverse, in particular non-thyroidal, health outcomes, but causality for most remains to be established.Methods: We combined individual level and summary level genetic prediction methods, i.e., polygenic scores and Mendelian randomization (MR), to systematically test for an association between liability to variat...

The functional state of the thyroid is usually determined by thyrotropin (TSH), whose serum levels depend on circulating thyroid hormone (TH) levels. This feedback mechanism is tightly controlled in the individual and contrasts broad reference range for TSH in the general population, leading to the concept of subclinical thyroid disease. We studied a model of experimental thyrotoxicosis in humans employing an untargeted metabolome and proteome approach. This allowed us to gain...

Background: Numerous animal models have shown impressive beneficial metabolic effects of the putative thyroid hormone (TH)-derivative 3,5-diiodothyronine (3,5-T2), including the prevention of insulin resistance or the reversal of hepatic steatosis, in the absence of thyrotoxic side effects. In contrast, the endogenous fate of 3,5-T2 in humans is still unclear. Comprehensive molecular profiling holds promise to gain deeper insights in metabolic alterations associated with serum...

Objectives: THRA mutations cause Resistance to Thyroid Hormone α (RTHα), an underdiagnosed disorder with hypothyroid features but near-normal thyroid function tests (TFTs). We developed a pathway, combining molecular analyses, new biomarkers and physiological measurements, to better diagnose and treat this disorder.Methods: Structural and functional analyses of THRA variants, discovered by next generation sequencing in specifi...