ESPE Abstracts

Background: IGF1 is mainly sequestered in a 150 kDa ternary complex with IGFBP3 and the acid-labile subunit (ALS). Dissociation of IGF1 from the ternary complex is in part regulated by proteolysis of IGFBP3, which reduces its affinity for IGF1. Short children born SGA have lower IGF1 and IGFBP3 levels compared to healthy peers.Objective and hypotheses: To determine complex formation in healthy normal statured children, and assess variables influencing co...

Background: Heterozygous GHR gene variants were found in 5–8% of idiopathic short stature (ISS) children. Frequent polymorphisms within GHR coding regions, but not intronic SNPs, have been investigated in ISS.Objectives: To characterize GHR gene variants in ISS children, and to test their influence on height and the peripheral GH/IGF1/IGFBPs system.Methods: GHR gene (coding/intronic flanking...

Background: GH is secreted in a pulsatile manner. The resulting GH peaks are known to be associated with growth, whereas the trough levels between the peaks are thought to be associated with metabolism in different tissues. GH trough levels were identified as a metabolically active signal in rats in the 1980th leading to differences in fat patterning with central obesity. Obese children are known to have low bone mass and bone mass is reduced in short children.<p class="ab...

Introduction: Complete ALS deficiency (ALS-D), caused by inactivating mutations in both IGFALS gene alleles, presents severe IGF1 and IGFBP3 deficiencies associated to moderate growth retardation.Aim: To characterize the molecular defect in a family where the index case and his father presented short stature and IGF1 and IGFBP3 deficiencies.Methods: IGF1, IGFBP3, and GH serum levels were determined by CLIA, ALS by ELISA an...

Background: A reduced GH response to different stimulation tests have been documented in both children and adults with Prader–Willi syndrome (PWS), independently from obesity. Previous reports suggested the hypothesis of an age dependent derangement of the hypothalamus–pituitary axis occurring in PWS subjects.Objective and hypotheses: In this longitudinal study we re-evaluated the GH responsiveness to a combined test after long-term GH therapy ...

Background: Patients with mutations of the short-stature-homeobox-containing (SHOX) gene likely have impaired growth, with or without a spectrum of skeletal anomalies consistent with mesomelic skeletal dysplasia. In a multinational clinical trial, GH has been shown to increase growth rate and final height (FH).Objective and hypotheses: The aim of this analysis was to describe FH outcome after GH treatment in an observational setting (Genetics and Neuroen...

Background: Recent studies have suggested a role of IGF1 as a candidate prognostic marker for cardiometabolic complications of obesity.Objective: To investigate the relationship between IGF1 serum levels and both biochemical and metabolic parameters as well as body composition in a cohort of obese children.Methods: obese subjects (130F/157M), aged 11.2±2.7 years, were studied. Anthropometry, biochemical and metabolic parameter...

Background: The GH/IGF1 axis has important roles in growth, metabolism, lipid profile and body composition. GH receptor disrupted mice (GHRKO mice) are resistant to the action of GH, thereby, GHRKO mice are dwarf, hypoinsulinemic, hypoglycemic and obese. Consumption of a high fat diet (HFD) induces inflammatory processes in a multitude of peripheral tissues, including hypothalamus.Objective and hypotheses: Our aim was to evaluate the effect of HFD intake...

Introduction: Previous reports support the hypothesis of an age dependent derangement of the hypothalamus–pituitary axis occurring in PWS subjects. In this context, transition years represent an important phase of growth process when somatic development reaches its completion. In the general population, GH deficiency (GHD) during the transition phase is associated with deterioration of body composition, metabolic alterations and reduced bone mineral density. PWS subjects ...

Background: Silver Russell syndrome (SRS) is characterized by low birth weight, severe postnatal short stature and distinctive facies. In ~50% of patients, (epi)genetic alterations can be detected (~40% hypomethylation of H19 on chromosome 11, ~10% maternal uniparental disomy (UPD) 7). As SRS patients are usually born small for gestational age (SGA), they are treated with GH to improve height. However, data on long-term effects of GH treatment in SRS patients are very limited....

Background: GH treatment is effective in improving adult height (AH) in short children born Small for Gestational Age. If SGA children are short at the start of puberty, they could benefit from combined GH/GnRH Analogue (GnRHa) treatment.Objective and hypotheses: To determine the timing and progression of pubertal development in short SGA children, comparing GH treatment with combined GH/GnRHa treatment.Method: For the present stud...

Background: Recombinant human GH (rhGH) is normally administered as a daily s.c. injection. NNC0195-0092 is a reversible albumin-binding GH derivative developed with the aim of reducing clearance and thereby extending the exposure. It has previously been demonstrated that NNC0195-0092 is well tolerated in healthy subjects with the potential for once weekly administration.Objective and hypotheses: In this trial NNC0195-0092 was administrated subcutaneousl...

Background: Treating central precocious puberty with GnRH agonist (GnRHa) to increase height gain is well-established. Although not recommended, GnRHa have also been used in patients with IGHD at onset of puberty yet there are few data on its efficacy.Objective and hypotheses: Growth prediction models derived from KIGS (Pfizer International Growth Database) may provide an opportunity to estimate additional height gain produced by pubertal blockade.<p...