ESPE Abstracts

Background: Insulin-like growth factor I (IGF-I) is one of the important hormonal mediators of human growth. Circulating IGF-I exists in a ternary complex bound to the acid-labile subunit (ALS) and one of its six binding proteins (BPs). IGF-I bound to ALS and BPs needs to be liberated by either Pregnancy Associated Plasma Protease A (PAPP-A) or A2 (PAPP-A2) to reach its receptor. Stanniocalcin 2 (STC2) is a potent inhibitor of both PAPP-A and PAPP-A2. Genome-wide association s...

Background: The type I IGF1R plays a role in intrauterine and postnatal growth. Heterozygous IGF1R mutations have been identified in over 20 families. Some of them are linked to the etiology of short stature in previous studies. In addition, we previously reported that a heterozygous nonsense mutation (p.Q1250X) of the IGF1R gene led to decrease IGF1R protein expression through endoplasmic reticulum-associated protein degradation (ERAD) mechanism, resulted in...

Background: Silver Russell syndrome (SRS) is genetically heterogenous and around 30% of patients with clinical SRS have no genetic diagnosis. Mutations in HMGA2 have recently been identified causing growth failure and an SRS-like phenotype. Despite strong evidence of the crucial role of HMGA2 in growth across species, the mechanism of action of HMGA2 in human linear growth is unclear.Objective:...

Background: Silver Russell syndrome (SRS) is a heterogeneous disorder characterised by intrauterine and post-natal growth retardation, relative macrocephaly, protruding forehead, feeding difficulties and body asymmetry. Variants in HMGA2 are a rare cause of SRS and despite strong evidence for the crucial role of HMGA2 in growth regulation, its functional role in human linear growth is unclear.Methods: Patients w...

Circadian clock system is an evolutionarily conserved system, by which organisms adapt their metabolic activities to environmental inputs including nutrient availability. The master pacemaker of the clock system is located in the suprachiasmatic nucleus (SCN) in the hypothalamus. The neurons in the SCN are entrained by the signals from the light through the retinal-hypothalamic tract and the light-dark cycle of the environment creates the rhythmic patterning of behavioral and ...

Background: Children born SGA have been implicated to be at higher risk for subsequent obesity; however, the body composition, especially fat distribution, in SGS short stature (SGA-SS) patients and the effects of growth hormone (GH) therapy on body composition in SGA-SS have not been fully studied.Purpose: To unravel the effects of GH therapy on body fat mass, body fat distribution, muscle mass, and bone mineral density...

Background: The Prader and Quigley classifications (P/Q-C), used widely to evaluate external/internal genitalia in differences/disorders of sexual development (DSD) patients, are sometimes unsuitable for determining the stage/grade because they were originally designed to assess 46,XX 21-hydroxylase deficiency (21OHD) and 46,XY androgen receptor defects (ARD), respectively. The external masculinization score (EMS) is also used to assess masculinization of the ...

Background: We have proposed a simple and comprehensive scoring system to evaluate clinical features of differences/disorders of sexual development (DSD); however, its clinical evaluation has not been performed.Aim: To evaluate the association between this newly proposed DSD scoring system (DSD-SS) and assigned gender in patients with 45,X/46,XY mosaicism.Methods: DSD-SS involves e...

Norditropin® was approved for children with short stature due to NS in Japan in 2017. The aim of this post-marketing surveillance study was to evaluate long-term safety and effectiveness of Norditropin® for the approved indication. This real-world non-interventional study (NCT03435627) was conducted February 2018–January 2022. Seventy patients enrolled: 35 received Norditropin® after study initiation (new patients); 35 were previously ra...

Treatment of short stature in children born small for gestational age (SGA) requires daily growth hormone (GH) injections that can be burdensome for patients and caregivers. Once-weekly somapacitan is a long-acting GH in phase 3 development for replacement therapy in children with GH deficiency. We report the 52-week results of the first phase 2, multinational, randomised, open-label, controlled, dose-finding trial (NCT03878446) investigating efficacy and safety of somapacitan...