Endocrine Abstracts

Hypothyroidism is the most frequent innate endocrine disorder, reaching a prevalence of 1 in 1200 newborns. Defects causing hypothyroidism occur at any level of the hypothalamus-pituitary-thyroid axis, but also at peripheral tissues, where alterations of intracellular transport, deiodination or nuclear action of thyroid hormone have been described in humans.In recent decades, molecular research found evidence that hypothyroidism is a genetic disease. Def...

Generation of hydrogen peroxide (H2O2) in thyroid cells is essential for the synthesis of thyroid hormone. H2O2 is produced by the Dual Oxidase 2 (DUOX2) at the apical membrane of the thyrocyte, where it is required by thyroperoxidase for the iodination of thyroglobulin. A dual oxidase maturation factor 2 (DUOXA2) was recently identified as an endoplasmic reticulum-resident protein required for expression of DUOX2 activity. DUOX2 and...

Thyroid hormone (TH) synthesis requires iodine, a scarce element whose recycling is mediated by DEHAL1 through deiodination of iodotyrosines MIT and DIT. In humans, DEHAL1 defects lead to severe congenital hypothyroidism (CH) non-detected by neonatal screening programs, which involves the risk of mental retardation in infants. The timing for establishment of this hypothyroidism remains unknown, but environmental iodine deficiency may represent a triggering factor. Whi...

Background: Most thyroid specific genes are transcriptionally regulated by TSH-TSHR signalling and T4-driven negative feedback of TSH secretion at the pituitary. However, local autoregulation of transcription has been described from IGF-IGFR, follicular thyroglobulin, or iodine. We aimed to investigate the TSH dependency of thyroid transcriptional regulation in the Dehal1 knockout, devoid of iodide-recycling capacity from iodotyrosines.Methods: ...

Generation of H2O2 at the apical membrane of thyroid cells is essential for iodination of thyroglobulin. Dual oxidase 2 (DUOX2) is the catalytic core of the thyroidal H2O2 generator, and its deficiency leads to congenital hypothyroidism (CH) in humans and mice. The Dual oxidase maturation factor 2 (DUOXA2) is a recently identified endoplasmic reticulum (ER)-resident protein required for expression of DUOX2 activity.<p class="abst...

Cinacalcet decreases and normalizes serum calcium levels across a broad severity range of primary hyperparathyroidism (PHPT), slightly reduces parathyroid hormone levels which generally remains elevated, whereas it has no effect on bone mineral density (BMD). Therefore, when administering cinacalcet to a patient with PHPT, concomitant treatment with an anti-catabolic drug should be considered.An open-labeled, prospective trial was conducted in 32 patient...

Thyroid hormones (TH) synthesis requires iodine, a scarce element whose recycling is mediated by the iodotyrosine dehalogenase (encoded by the DEHAL1 gene) through deiodination of mono- and di-iodotyrosines. In humans, biallelic mutations in DEHAL1 lead to a severe form of congenital hypothyroidism (CH) non detectable by neonatal screening programs, which involves the risk of mental retardation. The timing and triggering factors of this particular type of hyp...

Somatostatin is a pleiotropic neuropeptide that governs multiple biological targets, including tumor cell function, through a family of G protein-coupled receptors with 7-transmembrane domains (TMD), named sst1-5. However, we recently discovered sst5TMD4, an aberrantly spliced, truncated (only 4-TMDs) sst5-variant displaying unique molecular/functional features. sst5TM4 is overexpressed in various endocrine-related tumors exacerbating their malignant characteristics. Here, we ...