IMPE Abstracts

Context: Premature adrenarche in girls is defined biochemically by an increase in adrenal androgen (DHEA and DHEAS) levels above the age-specific reference range before age 8 years. Recently, increased levels of 11-oxyandrogens have also been observed in girls with premature adrenarche. On the other hand, epigenetic control of some genes that code for enzymes that participate in the synthetic pathway to 11-oxyandrogens (e.g., CYP11B1) has been describ...

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. The LUM-201 predictive enrichment marker (PEM) may be used to identify patients previously diagnosed with iPGHD who are likely to respond to LUM-201. PEM positivity is defined as a 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...

Perceived diabetes stigma (PDS) has been associated with worse clinical and psychosocial outcomes in adults. Our objective was to examine the associations between PDS, glycemic control, diabetes complications, psychosocial variables, and substance use in adolescents and young adults (AYAs) with type 1 diabetes (T1D) and type 2 diabetes (T2D) in the SEARCH for Diabetes in Youth study, 2016-2019. We hypothesized that greater PDS was associated with worse glycemic control, greate...

Nuclear receptor subfamily 5 group A member 1 (NR5A1), is a member of the nuclear receptor family. It plays a crucial role in transcriptional regulation of genes involved in steroidogenesis, gonadal development and reproduction. NR5A1 mutations represent one of the most frequent defects associated with 46,XY gonadal dysgenesis, associated with a wide phenotypic spectrum of DSD. Some patients with mutations in the NR5A1 may have normal testosterone le...

Introduction: Children classified as idiopathic short stature (ISS) may have a monogenic cause that can explain their growth disorder. In this context, genetic tests emerge as a new diagnostic tool. Objectives: To determine the usefulness of WES for the genetic investigation of children with ISS.Patients and Methods: We sequentially enrolled 95 children with ISS without previous genetic testing, except for karyotyping fo...

Background: Vosoritide increases annualized growth velocity (AGV) in children with achondroplasia aged 5 to 18 years. This global, phase 2, randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of vosoritide on growth in children with achondroplasia aged 3 months to <5 years.Methods: This study compared once-daily subcutaneous administration of vosoritide, at doses of 15 or 30 mg/kg of b...

Background: Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia, affecting between 1 in 15,000 to 1 in 30,000 live births. People with ACH are at risk for several significant co-morbidities, including foramen magnum stenosis, obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis, and a propensity towards obesity. PROPEL is a prospective, non-interventional study designed to examine baseline growth param...

Background: Achondroplasia (ACH) is the most common form of short-limbed skeletal dysplasias and is caused by an activating pathogenic variant of the fibroblast growth factor receptor 3 (FGFR3) gene. People with ACH are at risk for several significant co-morbidities, including foramen magnum stenosis, obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis, and a propensity towards obesity. Decreased bone mass was r...

Background: Bone age (BA) is commonly used in pediatrics to define skeletal maturity for medical and non-medical purposes. Normal range is represented by 2 standard deviations (SDs) &pm; the mean. A BA > &pm;2 SDs from the chronological age (CA) is considered abnormal. BA in achondroplasia (ACH) has not been fully characterized; calculation is challenging given difficulties in comparing x-rays with standard radiographs if using the Greulich-Pyle (G&P) m...

Objectives: Vosoritide is a potent stimulator of endochondral bone growth and is in development for the treatment of achondroplasia, the most common form of disproportionate short stature. We previously reported on a 52-week, phase 3, pivotal study that demonstrated a significant improvement in annualized growth velocity (AGV) when vosoritide was compared to placebo in children with achondroplasia aged 5-18 years (Savarirayan et al, Lancet, 2020). Thi...