Endocrine Abstracts

Background: Resistance to thyroid hormone alpha (RTHα), caused by mutations in the T3-receptor alpha 1 (TRα1) isoform, includes growth retardation, intellectual disability, and abnormal thyroid function tests. The current paradigm entails that disease features arise from decreased T3 action in TRα1-expressing tissues. However, also for patients that carry mutations that completely abolish T3-stimulated activity, neurological features vary strongly, ranging from ...

The adrenal gland produces corticosteroids essential for hydromineral and metabolic homeostasis. It is organised, in mice, in two concentric layers. The zona glomerulosa (zG) and fasciculate (zF), renewed from progenitors located in the capsular periphery. Centripetal renewal and maintenance of cortical zonation are dependant of a balance between WNT/β-catenin and ACTH/PKA signalling pathways. They provide recruitment and consecutive differentiation of progenitors into zG...

Iodine is a trace element required for thyroid hormone production. Requirements increase in pregnancy, when even mild deficiency may affect offspring neurocognitive development.The gold standard for assessing iodine status is population surveys of urinary iodine concentration (UIC). The WHO also suggests a population prevalence of >3% of TSH values > 5 mIU/L indicates deficiency. A recent UK survey of 700 teenage girls demonstrated ...

Iodine is a trace element required for thyroid hormone production. Requirements increase in pregnancy, when even mild deficiency may affect offspring neurocognitive development.The gold standard for assessing iodine status is population surveys of urinary iodine concentration (UIC). The WHO also suggests a population prevalence of >3% of TSH values > 5 mIU/L indicates deficiency. A recent UK survey of 700 teenage girls demonstrated ...

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: MCT8 deficiency is caused by loss-of-function (LoF) mutations in thyroid hormone (TH) transporter MCT8. Patients have developmental delay and abnormal thyroid function tests (TFTs). The large phenotypic variability is not understood. Moreover, phenotypes arising from LoF mutations could be employed to enhance understanding of physiology in the general population. Also, computational disease variant classifiers have poor predictive power to ascertain impact of MCT8 ...

Background: Neuroendocrine neoplasms (NEN) are known to be associated with specific familial syndromes. However, the incidence of pathogenic germline variants (PGVs) in unselected NEN patients is unknown. In this study, we aim to determine the prevalence and clinical utility of PGVs in unselected NEN patients using universal a genetic testing approach.Methods: We undertook a prospective study of germline genetic testing using a > 80 gene next-generat...

Introduction: Adequate thyroid hormone availability during early life is crucial for normal child growth and development. Fetal growth in utero heavily depends on angiogenesis. Placental growth factor (PlGF) is a proangiogenic factor sharing high homology with vascular endothelial growth factor (VEGF) whereas soluble FMS-like tyrosine kinase-1 (sFlt1) is a potent antagonist of VEGF and PlGF signaling. Since the thyroid is a highly vascularized organ, we hypothesized t...

Background: FOP is an ultra-rare, severely disabling genetic disorder characterised by cumulative heterotopic ossification (HO), often preceded by episodic flare-ups, leading to physical disability and early death. Initial misdiagnosis can occur in ~90% of individuals leading to unnecessary, often harmful interventions. FOP is diagnosed and managed by multiple specialists, including endocrinologists.Objective: A prospective, 36-month, global natural...

Obesity is a growing global epidemic and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs which aim to cause effective weight loss with minimal side effects. Two related peptide hormones, glucagon and glucagon-like peptide 1 (GLP-1), are the subject of this investigation. Both have been found to reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. It is...