Endocrine Abstracts

Thyroid hormone receptors (TRs) modulate various physiological functions in many organs. The conservation of TRα and TRβ isoforms during evolution of vertebrates suggests different roles for these TRs in thyroid hormone-dependent regulation of gene expression. TRα and TRβ are widely distributed and overlapping in several tissues, and their functional divergence is mainly attributed to their variable tissue expression patterns and intrinsic properties of spe...

The thyroid hormone (TH) feedback is the principal mechanism contributing to maintain the circulating levels of thyroid hormones within the physiological limits that are required for an adequate action at the tissue level. Therefore, circulating TSH determination is considered the most accurate parameter to diagnose a disorder of thyroid function. Several defects are known to be associated with the disruption of such mechanism, but their intimate understanding is still limited...

Anaemia in RTHα patients correlates with documented abnormal erythropoiesis and reduced haematocrit in TRα-null or mutant mice, but the underlying mechanisms and characterization of the defect remain elusive. In a previous work, we described that the injection of several hTRα variants in zebrafish eggs caused a marked reduction of circulating erythrocytes at later stages of the erythropoiesis. To characterise the involvement of TRα during erythrocyte develo...

Introduction: Since 2012, different heterozygous mutations in the THRA gene have been described in patients with resistance to thyroid hormone alpha (RTHα). The associating symptoms are reminiscent of untreated congenital hypothyroidism (growth retardation, psycho-neuromotor disorders, delayed bone development and bradycardia) but with raised T3/T4 ratio and normal TSH levels. All genetic abnormalities act in a dominant negative (DN) manner against functional rec...

Patients with resistance to thyroid hormone β (RTHβ) often display a neurocognitive phenotype, but the underlying biological defects have not been characterized. The predominant receptor isoform expressed in brain tissue is TRα1 leading to the assumption that this receptor accounts for most of the T3 effects. Nevertheless, TRα and TRβ are both expressed in brain therefore our study aims to understand the impact of a mutant THRβ on TH action in the...

Thyroid hormone (TH) action is required for the adequate brain development. While TRα1 is recognized as the predominant receptor mediating most of these effects in brain tissue, the expression of both TRα and TRβ during development prompts further examination on their respective role. The study aims to investigate the role of TRβ during cortical neuron differentiation, taking advantage of induced pluripotent stem cells (iPSCs) obtained from patients with re...

Objective: decreased survival and higher cardiovascular risk have been reported in a UK cohort of RTHβ patients, but there is no evidence from other countries.Methods: retrospective study of an Italian cohort of RTHβ patients, carrying heterozygous pathogenic variants in the THRB gene and diagnosed in the period between 1984 and 2023. We collected records at diagnosis of 284 cases, whereas longitudinal data were available in 249 RTH&#9...