Endocrine Abstracts

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...

Adult-onset hypothyroidism is associated with cognitive dysfunction, and a significant fraction of hypothyroid patients still shows persistent disturbances despite standard T4 replacement therapy. Experimental results showed that tissue levels of T4 metabolites, particularly T1AM, are decreased in hypothyroidism and remain low after T4 replacement. Thyroid hormones are important for the promotion of neurogenesis and neuron migration to different areas of the cerebral cortex, i...

Congenital Hypothyroidism (CH) is the most common congenital endocrine disease and avoidable cause of severe mental retardation. The CH pathogenesis may include the contribution of genetic and environmental factors. However, causal mutations have been found in a minority of cases. Moreover, the elevated frequency of discordance for CH phenotype between monozygotic (MZ) twins suggests the involvement of non-Mendelian mechanisms. Aim of this study was to investigate the role of ...

Objectives: During prenatal neurodevelopment, maternal-to-fetal thyroxine (T4) transfer is critical, particularly during the first half of pregnancy when the fetal thyroid gland is immature. Transcellular transport of thyroid hormones (TH) is facilitated by TH transporters. Monocarboxylate transporter 8 (MCT8) is a specific TH transporter that is crucial for transport of TH with a prominent expression at the blood-brain barrier. MCT8 deficiency is a rare disorder consisting of...

Background: Previously, we identified a novel gene, BOREALIN/CDCA8 in congenital hypothyroidism. Patients with BOREALIN mutations had thyroid dysgenesis, from asymmetric lobes to athyreosis (Carré et al. Hum Mol Genet 2017). Borealin is a major component of the Chromosomal Passenger Complex, an essential regulator of mitosis. We demonstrated a new feature of BOREALIN: involvement in the adhesion and the migration of the thyrocytes.<...