Endocrine Abstracts

Treatment for congenital hypothyroidism (CH), based on thyroid extracts, was introduced more than 100 years ago and resulted in a compelling improvement of impaired growth, obesity, depression and severe delay of motor development. However, severe mental retardation remained despite treatment. It was only after the implementation of neonatal screening for CH in 1970s that intellectual outcomes improved to an average normal IQ. However, whether complete normalization of cogniti...

The highly conserved Leptin-Melanocortin signaling pathway plays a central role in the regulation of body weight and energy expenditure. Mutations in POMC and MC-4R lead to dosage dependent monogenetic obesity. However, several evidences suggest an epigenetic impact on the regulation of body weight. Moreover it has been shown recently that variants of the FTO gene, which affects ss DNA methylation in the arcuate nucleus, correlate with increased body weight in children and adu...

Isolated growth hormone deficiency (IGHD) type 1a is caused by defects of the GH-I gene resulting in severe short stature. Treatment with growth hormone may become ineffective due to significant production of growth hormone antibodies. However, this has only been reported in patients treated with pituitary derived growth hormone. We present five cases with IGHD type 1a successfully treated with recombinant human growth hormone (rhGH).Five patients from f...

Background: Current standard treatment for adrenal insufficiency in neonates and infants is unsatisfactory as unlicensed adult dosage formulations are used. These are generally difficult to administer and may give rise to inconsistencies in dose as the content uniformity of the dosage form cannot be verified.Methods: Infacort is a newly-developed immediate release formulation of hydrocortisone that is provided in appropriate unit dosage units (0.5, 1, 2,...

In two siblings suffering from congenital hypothyroidism we identified a homozygous missence mutation Ala579Val in transmembrane helix 5 of the thyrotropin receptor (TSHR) gene which motivated us to investigate molecular details of this mutation.We were interested, firstly, in the functional effects regarding signal transduction and, secondly, in the particular structural properties of the wild type receptor and the Ala579Val mutant. The aim was to gain ...

Background: Defective thyroid gland development occurs in 80% of congenital hypothyroidism (incidence of 1:3000–1:4000). Only <5% have been shown to be caused by molecular genetic defects in few transcription factor genes (Nkx2.1, Nkx2.5, Foxe1, Pax8, Hhex) which are known to play a role in thyroid gland development. Therefore, other genes with a critical role in early thyroid development are likely to be involved in the pathogenesis of thyroid dysgenesis.<p class...

Objective: The NKX2-1 gene, also known as TITF-1, TTF-1 or T/ebp, is a member of the homeodomain-containing NK-2 transcription factor gene family and expressed in early development of thyroid, lung and forebrain. Initial screening of patients with isolated congenital hypothyroidism failed to show mutations. The first human heterozygous deletion affecting the NKX2-1 gene to be reported was a neonate with respiratory failure, primary hypothyroidism and neurological signs matchin...

Background: It becomes increasingly evident that features of the metabolic syndrome are already present in young obese patients. Especially an impaired glucose metabolism with insulin resistance is an alarming sign of existing comorbidity of childhood obesity. Metformin has been argued as one pharmacological option to improve impaired glucose metabolism at least in obese adults. So far three prospective randomized studies were performed in childhood cohorts with <30 patien...

Introduction: Children with adrenal insufficiency requiring hydrocortisone rely on compounded adult medication. This study aimed to evaluate the absorption, palatability and safety of Alkindi® (hydrocortisone granules in capsules for opening).Methods: The phase 3 study was an open-label, single-dose study in a total of 24 children (aged 0–6 years) with adrenal insufficiency. Fasted children were given a single dose of Alkindi&#1...

Clinical Endocrinology, 2018, 88(1): 21–29 (DOI: https://doi.org/10.1111/cen.13447)...