Endocrine Abstracts

Long-acting somatostatin analogues normalize serum IGF-I levels in about 65% of acromegalic patients. Somatostatin analogs reduce GH secretion but also induce GH resistance of the liver because of low portal insulin levels; i.e. patients have a relative high GH level and a GH resistance of the liver which results in a relative low IGF-I action because of high IGFBP1 levels, but the other tissues still have normal GH sensitivity. One might predict that long-term follow-up of tr...

Introduction: Adequate hormone replacement therapy in adrenal insufficiency is essential. Patients should have basic knowledge about their condition and what to do in situations which could trigger an adrenal crisis. Education on how and when hydrocortisone replacement therapy should be adjusted as well as instruction and practice an emergency injection are considered important measures to prevent an adrenal crisis. A standardized nurse-led group-based education programme (GEP...

Medical treatment of acromegaly is based on either suppressing pituitary GH secretion or inhibiting GH action by preventing interaction with its receptor in order to suppress the elevated levels of IGF1. AZP-3813 is a 16-amino acid, bicyclic peptide antagonist of the GH receptor (GHR) derived from peptide sequences discovered using a unique, cell-free in vitro transcription-translation system screened against the human GHR, and that was optimized by rational design to increase...

The key metabolic hormone, leptin, acts in part through the liver to regulate glucose homeostasis, as well as the maturation of both adipocytes and osteoblasts. These actions have been demonstrated to be mediated by insulin-like growth factor binding protein 2 (IGFBP-2), independent of its ability to bind IGF1. The effects of IGFBP-2 on adipocyte and osteoblast maturation can be localized to a short peptide sequence within the unique heparin binding domain (HBD-1) of IGFBP-2. ...

Background: Efficacy and safety of combination treatment of pasireotide LAR with pegvisomant (PEGV) has not been studied yet. Switching to Pasireotide LAR in patients previously controlled with long-acting somatostatin analogues (LA-SSAs) and PEGV could reduce the required PEGV dose to normalize serum IGF1 levels, while the effect on glucose metabolism is unknown.Methods: We enrolled 60 acromegaly patients >18 years with acromegaly who had normal IGF...

The peptides acylated and unacylated ghrelin (AG and UAG) are produced predominantly in the stomach. AG is the only known circulating orexigenic hormone with obesogenic and insulin-desensitising properties. Recent evidence suggests that UAG can inhibit these activities of AG. To investigate potential inhibitory effects of UAG and AZP-531, a UAG analogue, on AG-induced appetite and obesity we used an established rat model of diet induced obesity. Animals were fed a high-fat die...

Introduction: Prader-Willi syndrome (PWS) is a complex hypothalamic disorder, combining hypotonia, intellectual disability (ID), pituitary hormone deficiencies and hyperphagia. In PWS, up to 3% of patients die every year. In half of the patients, the cause of death is obesity related and / or of cardiovascular origin. Obesity is caused by hyperphagia combined with a low energy expenditure. Untreated hormone deficiencies like hypogonadism and hypothyroidism can cause low muscle...

Objective: Acromegaly is caused by a growth hormone (GH)-secreting pituitary tumor and its signs are linked to increasedGH-dependent hepatic insulin-like growth factor I (IGF-I) synthesis. A eucaloric very low-carbohydrate ketogenic diet (euVLCK; < 50 g/day) induces ketosis and reduces portal insulin concentrations, which down-regulate hepatic GH receptors and reduce IGF-I synthesis. Somatostatin receptor ligands (SRLs) reduce GH secretion by the pituitary tumor,resul...

Ghrelin, the endogenous GH secretagogue, has an important role in metabolic homeostasis. It exists in two major molecular forms: acylated (AG) and des-acylated (DAG). Many studies suggest different roles for these two forms in energy balance regulation. In the present study, we compared the effects of acute intracerebroventricular (ICV) administration of AG, DAG and their combination (AG+DAG) to young adult Wistar rats on food intake and central melanocortin system modulation....

Introduction: Pegvisomant (PEGV) has an efficacy of >90% to control insulin-like growth factor (IGF-1), however in everyday practice a limited efficacy of 63% was reported.Aim: To assess efficacy in the largest single center cohort of acromegalics using PEGV.Methods: A 112 subjects (65 male) were not controlled with high-dose somatostatin analogues (LA-SRIF) for at least 6 months. To control acromegaly, 109 subjects added PEGV ...