IMPE Abstracts

Congenital hyperinsulinism (CH) is the occurrence of hypoglycemia due to insulin secretion unrelated to glycemic level. The prevalence of this disease is not known in Brazil and there is no report of clinical characteristics of the cases. The Congenital Hyperinsulinism Association (HIC) was created by parents of children with CH. In order to know the clinical and demographic characteristics of children and adolescents with CH, a standard questionnaire was designed to be applie...

The growth hormone (GH)-insulin-like growth factor (IGF-1) axis determines growth during different stages of life. Mutations resulting in deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), a protease involved in the release of free IGF-1, leads to problems in growth, reduced bone density and body mass and mild glucose intolerance. To better understand the physiological role of PAPP-A2, we analyzed the metabolic status and lipid metabolism in a mouse model of homoz...

The accelerated growth phase observed during puberty depends on the combined effects of the somatotropic and gonadotropic axes. Our previous studies have demonstrated that relatively low concentrations of estradiol (20 pg/mL) and high concentrations of testosterone (10 ng/mL), potentiate the JAK2/STAT5 signaling pathway induced by GH in the human hepatic cell line (HEPG2). It is not known whether these effects are direct, or are mediated through the suppressors of cytokine sig...

Introduction: GH1 was the first gene associated with isolated GH deficiency (IGHD) due to a gene deletion described in 1981. Subsequently, frameshift, homozygous missense and nonsense allelic variants, and splice site allelic variants causing GHD were reported.Aim: Use whole exome sequencing (WES) in the search of variants in known genes and also new genes associated to IGHD and determine the effect of variants....

Background: IGF-1 receptor (IGF-1R) is widely expressed across many cell types in fetal and postnatal tissues. IGF-1R activation by IGF-1 and IGF-2 generates several responses including proliferation, and the protection of cells from apoptosis. Signaling through IGF-1R is the principal pathway responsible for somatic growth in fetal mammals, whereas in postnatal animals is achieved through synergistic interaction of growth hormone and the IGFs. IGF-1R gene mut...

Background: Lonapegsomatropin (TransCon hGH) is a once-weekly prodrug of somatropin, approved for the treatment of pediatric growth hormone deficiency (pGHD) by the US FDA and EMA. In the pivotal phase 3 heiGHt trial, lonapegsomatropin demonstrated noninferior and superior annualized heigh velocity (AHV) and a comparable safety profile to daily somatropin in children with GHD. The ongoing open-label extension trial, enliGHten, enrolled participants from the he...

LUM-201 (ibutamoren), an agonist of the growth hormone (GH) Secretagogue Receptor 1a (GHSR1a), is an investigational oral GH secretagogue currently in three iPGHD Phase 2 trials. A LUM-201 predictive enrichment marker (PEM) may be used to select previously diagnosed iPGHD patients likely to respond to LUM-201. PEM positivity is defined as baseline insulin-like growth factor-1 (IGF-1) level >30 ng/mL and a peak GH of ≥ 5 ng/mL in response to a single 0.8 mg/kg oral dose o...

Objectives: Although there are some recommendations in the literature on the assessments that should be performed in children on rhGH therapy, the level of consensus on these measurements is unclear. The objective of the current study was to identify the minimum dataset that could be measured in a routine clinical setting across the world.Methods: This exercise was undertaken through the GH Scientific Study Group (SSG) i...

During transition phase, pituitary hormones, particularly GH, play a relevant role on body composition and bone maturation. Aim: to evaluate the effect of rhGH discontinuation during this period, particularly regarding time without treatment, IGF1 levels and the presence of hydrocortisone concomitant therapy on body composition and bone mass. Fourteen transition GHD patients (females:7) were evaluated by dual X-ray absorptiometry (DXA) after a period of discontinuation. Multip...

Osteogenesis imperfecta (OI) is a genetic disease characterized by alterations in type I collagen, which determine a broad spectrum of clinical alterations. Although there is no specific treatment, drugs of the bisphosphonate class are used with the aim of improving bone quality with a reduction in fracture events and a gain in quality of life. In Brazil, current protocols use pamidronate, a second-generation bisphosphonate. The use of zoledronic acid, a third-generation bisph...