ESPE Abstracts

Background: The hepatokine FGF21 signals through a dual receptor complex consisting of FGFR1c and the obligatory co-receptor β-Klotho to regulate glucose and lipid metabolism. Interestingly, female mice with Fgf21 transgenic overexpression are not only resistant to high-fat diet induced obesity but also present with hypogonadotropic hypogonadism (HH) and infertility. Loss-of-function (LOF) mutations in FGFR1 are a frequent cause of congenital HH (CHH). W...

Background: Congenital diabetes insipidus (DI) can be due to mutations in the arginine vasopressin (AVP) gene (familial neurohypophyseal DI), the AVP receptor type 2 (AVPR2) or aquaporin 2 (AQP2) genes (congenital nephrogenic DI, NDI). The clinical manifestation of congenital NDI, especially the response to AVP, can vary greatly depending on the functional effect of the AVPR2 mutation. Here we present two male siblings with NDI and partial response to ddAVP.<p class="abste...

Background: The increasing number of transgender adolescents presenting in early puberty requires to investigate the effects of long-term puberty suppression and gender-affirming hormones (GAH) on body composition and metabolism. Clinical studies have ethical and practical limitations. A preclinical mouse model may be helpful to gain mechanistic insights.Methods: Prepubertal (4week-old) female mice were treated with the ...

Background: Transgender individuals increasingly present at gender services in childhood. Consequently, to suppress pubertal development, more adolescents are long-term exposed to gonadotropin-releasing hormone analogues (GnRHa), from onset of puberty until start of gender-affirming hormones (GAH), around 16 years. Prolonged GnRHa may compromise bone health more than shorter-term treatment. If earlier start of GAH, when psychologically indicated, may partially...

The high rate of false-positive (FP) results in congenital adrenal hyperplasia newborn screening (CAH-NBS) worldwide challenges NBS-programs and reinforces the need of high specificity subsequent tests. Few studies assessed the efficacy of different serum steroids by the available methodologies. Serum 21-deoxycortisol-21DF demonstrated a high diagnostic accuracy in CAH children/adults but was not evaluated in the NBS context. Objective: to evaluate the efficacy of confirmatory...

Background: An activation cascade of specific genes sets up the initiation of sex determination leading in males to testes formation and synthesis of testicular hormones. Disruption of this gene cascade may cause a spectrum of disorders/differences of sex development (DSD) phenotypes. Here we describe for the first time two sisters suffering from 46,XY DSD, who by whole exome sequencing were shown to carry a mutation in the X-linked StAR-related lipid transfer...

Here, we report on a female adolescent with overweight and a very high DHEAS serum level. The hypothesis that the origin of DHEAS excess was the presence of either an ovarian or a suprarenal DHEAS-producing tumor was not confirmed. Sonographic and MRT investigations did not support its presence. In addition, effective dexamethasone suppression of DHEA and DHEAS excluded this diagnosis. Steroid sulfatase (STS) hydrolyses alkyl and aryl steroid sulfates to their unconjugated for...

Introduction: Since 2000 understanding of biology of sex development increased tremendously thanks to genetic research. This lead to new classification for persons with disorders/differences of sex development (DSD) based on genetics, and guidelines from the UK recommend revising medical care for persons with DSD by setting up interdisciplinary DSD teams. In Switzerland, persons with DSD asked for better care, stimulating the Swiss National Ethics Commission in 2012 to recomme...

Background: Most congenital adrenal hyperplasia (CAH) patients carry mutations derived from conversion events involving the pseudogene, and the remaining carry new mutations varying according to ethnicity. A good genotype-phenotype correlation is observed, allowing the use of molecular analysis in clinical practice.Objective and hypotheses: To review the molecular diagnosis in a large cohort of CAH patients in order to create a diagnostic panel in our po...

Background: SOX2 is an early developmental transcription factor implicated in pituitary development; heterozygous SOX2 mutations have been reported in patients with a severe ocular phenotype and hypogonadotrophic hypogonadism (HH) with/without associated abnormalities. SOX2 physically interacts with β-catenin, a member of the Wnt-signalling pathway, via its carboxyl-terminus and it represses in vitroβ-catenin mediated activation.<p class="abstex...