IMPE Abstracts

Introduction: The genetic factors are frequently implicated in the growth impairment of short stature (SS) children, whether they are syndromic or apparently healthy. However, the investigation recommended by the consensus fails to establish the etiology in most cases. The difficulty to search for candidate genes increases the importance of using a hypothesis-free approach as whole exome sequencing (WES) for these children. Objective: To determine the diagnost...

Background: Somatrogon is a once-weekly treatment for children with pediatric GH deficiency (pGHD). The goal of this study was to simulate IGF-1 and IGF-1 SDS profiles and calculate the ratio and differences of observations to 96-hour values over the dosing interval.Methods: A population PK model was developed using data from a Phase 2 study and a Phase 3 study in children with pGHD. An indirect-response PK/PD model link...

Bardet-Biedl syndrome (BBS) is a rare disease associated with signaling defects in the melanocortin-4 receptor (MC4R) pathway that lead to hyperphagia, severe obesity, and, consequently, reduced quality of life (QOL). We investigated the impact of setmelanotide, an MC4R agonist, on weight, body composition, hunger, and QOL in a Phase 3 trial of patients with BBS to characterize clinically meaningful and patient-relevant benefit. Patients aged ≥6 years with BBS and obesity w...

Background: The leptin-melanocortin pathway regulates satiety and energy metabolism. Prohormone-convertase-1 (PCSK1) cleavage of hypothalamic proopiomelanocortin is an essential step in central leptin signaling and effects. The heterozygous N221D variant in PCSK1 is considered to increase obesity risk in humans through the decrease in enzymatic activity and/or loss of resilience to stressors and could also influence its role in proinsulin processing.<p cla...

Mechanisms underlying long-term sustained weight loss and glycemic normalization after obesity surgery involves changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). Designing dual or triple agonists based on glucagon-like peptide (GLP)-1 with glucagon, and/or glucose-dependent insulinotropic polypeptide (GIP) are promising novel approaches for anti-obesity drugs tackling different weight-regulatory pathways, albeit such developments co...

Background: Hepcidin is a protein that could be a link between iron and inflammation. Hepcidin sequesters iron, increasing intracellular ferritin, which promotes tissue damage through the cascade-amplified inflammation.Aim: To determine the association between hepcidin levels with inflammatory markers (PCR, ferritin, Lpa, and neutrophils), and glucose levels in indigenous school children living at 3750 m above sea level....

Background: Hyperandrogenemia resulting in estrogen-mediated accelerated bone maturation and early growth plate fusion largely contributes to short stature in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Aromatase inhibitors block androgen conversion to estrogen and have been used off-label in children with short stature to improve adult height. There have been no adequately powered studies supporting the use of aromatas...

Background: The adrenocorticotropic hormone (ACTH) is a 39 amino acid polypeptide secreted by the anterior pituitary and regulates cortisol secretion from the adrenal cortex. Cortisol has a negative feedback mechanism and regulates the biosynthesis and secretion of ACTH. Excess of ACTH is associated with a wide range of diseases including congenital adrenal hyperplasia (CAH). Classic CAH due to the 21-hydroxylase (CYP21A2) deficiency causes a reduction or loss...

Contemporary ACTH assays have variable susceptibility to interference by endogenous antibodies, particularly heterophile antibodies, leading potentially to unnecessary investigations1-6. Often, determining the cause of the spurious ACTH results is impossible beyond identifying the presence of interference of heterophile antibodies6. Here we describe two cases of Cushing Syndrome due to Primary Pigmented Nodular Adrenocortical Disease (PPNAD) whose evaluat...

Context: MIRAGE syndrome (OMIM #617053) is a multiorgan disorder including hypoplasia of the adrenal glands and gonads (Narumi S et al., Nat Genet 2016). The syndrome is caused by heterozygous pathogenic SAMD9 variants with potent growth-inhibitory activity. There is no effective treatment for the syndrome, and approximately 40% of documented cases die before age 3.Objective: We aimed to establish a screening me...