ESPE Abstracts

Background: Implementation of neonatal screening programs for congenital hypothyroidism (CH) has reduced related nosologies and has eradicated CH-associated mental impairment. With the decrease of the TSH cut-off limits employed to avoid false negative results, milder cases of CH are diagnosed. Obviously, in a number of patients, especially among milder CH cases, thyroid dysfunction is transient. The diagnosis of transient vs. permanent CH is established in time. No specific p...

Background: FOXE1 gene variants containing alterations in the alanine tract length may confer susceptibility to primary ovarian insufficiency (POI). BMP15 gene variants have also been related to POI.Objective and hypotheses: To evaluate the contribution of FOXE1 and BMP15 variants in the pathogenesis of POI and to investigate the hypothesis of digenic inheritance in this disorder.Method: FOXE1 and BMP...

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: A mutation in EIF2S3 (NM_001415; Xp22.11) was previously associated with microcephaly and developmental delay in a single pedigree. EIF2S3 encodes the eukaryotic translation initiation factor 2 subunit 3 (eIF2γ), the largest of three EIF2 subunits. EIF2 initiates protein synthesis by forming a ternary complex with GTP and initiator methionyl-tRNA which then binds to the 40S ribosomal subunit, enabling scanning of mRNA from the 5′ end to...

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...