ESPE Abstracts

Background: In humans, loss-of-function mutations in Nicotinamide nucleotide transhydrogenase (NNT) cause familial glucocorticoid deficiency, a potentially fatal, adrenal-specific disorder characterized by increased ACTH and reduced cortisol levels. NNT is a highly conserved inner mitochondrial membrane protein, which supplies high concentrations of NADPH for detoxification of reactive oxygen species (ROS) by glutathione and thioredoxin pathways.<p class="abstext"...

Background: DMXL2 haploinsufficiency in humans was recently shown to cause the polyendocrine-polyneuropathia syndrome including a GnRH deficiency (OMIM #616113). The neuronal deletion of Dmxl2 in mice (Nes::Cre;Dmxl2loxp/wt) caused infertility and gonadotropic deficiency (Plos Biology 9 e1001952, 2014). Dmxl2 encodes rabconnectin-3α (rbcn-3α), which participates in the control of the V-ATPase activity an...

Background: The Topicon™ patch is a needle-free novel platform technology developed to achieve truly passive transdermal delivery of insulin. Here we report pharmacodynamic (PD) and pharmacokinetic (PK) studies comparing needle injection (s.c.) vs Topicon™ mediated patch delivery of the insulin analog glargine (LANTUS®) in streptozotocin-induced hairless rats.Objective and hypotheses: We sought to develop a convenient, af...

Background: In order to prevent virilization in CAH female fetuses, physicians have during the last thirty years used the synthetic glucocorticoid dexamethasone (DEX) as a therapeutic approach administered during early pregnancy. Due to the fact that treatment has to be started before the genotype of the fetus is known, seven out of eight treated fetuses will be subjected to high doses of DEX during early embryogenesis without benefit. Therefore, negative side effects cannot b...

Background: IGF1 and IGF2 are major regulators of somatic growth acting mainly through the IGF1R. Variants in IGF1 and in IGF1R were identified to cause intrauterine and postnatal growth retardation but variants in IGF2 have not yet been reported.Method: In a multigenerational family four affected members (two siblings, one first degree cousin and the daughter of one sibling) exhibited severe growth retardation with heights between −4.2 and −...

Background: Congenital multiple pituitary hormone deficiency (MPHD) arises from defects in pituitary development and is sometimes associated with craniofacial abnormalities. Mutations in the transcription factor PROP1 are the most common known genetic cause of the disorder. In this case the course of disease is progressive, and can lead to life threatening adrenal insufficiency.Objective and hypotheses: Our objective is to understand the role of PROP1 in...