ESPE Abstracts

Background: Prenatal dexamethasone (DEX) treatment is in many countries offered to the pregnant woman, at risk of having a child with classic congenital adrenal hyperplasia (CAH), to reduce virilization in an affected female fetus. The treatment is effective in reducing virilization but may give long lasting effects on somatic and cognitive health. Here, we explore the potential effect on metabolism in children and adults not having CAH and exposed to DEX during the first trim...

Background: Increased risk of obesity and cardio-metabolic risk factors were reported in patients with classical congenital adrenal hyperplasia but little is known about adiposity among patients with non-classical congenital adrenal hyperplasia (NCCAH).Aim: To assess the prevalence of overweight, obesity and cardio-metabolic risk factors among NCCAH patients. Methods: A cross-sectional retrospective study of 114 NCCAH patients (93 ...

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders, affecting around 1/10 000 newborns worldwide. Postnatally, patients with classic CAH are treated with life-long glucocorticoid (GC) replacement therapy, such as hydrocortisone or prednisolone, and in the more severe cases also with mineralocorticoids. A negative impact of GCs on human cognition such as memory deficits have been reported bot...

Background: Congenital adrenal hyperplasia (CAH) is a relatively common monogenic recessive disorder with an incidence of 1/15 000 in most populations. It has been suggested that CYP21A2 deficiency is relatively common because it may confer a survival advantage to be a carrier. Carriers of CYP21A2 mutations typically do not have clinical symptoms but have a defined phenotype. The cortisol response to ACTH stimulation has been shown to be both...

Introduction: Congenital adrenal hyperplasia (CAH) is most often caused by 21-hydroxylase deficiency (21OHD: 95%) or by 11-hydroxylase deficiency (11OHD). Classic CAH results in impaired cortisol production and consequently elevated ACTH concentrations leading to chronic adrenal stimulation with strongly elevated adrenal steroid precursors before the enzymatic defect. In contrast to other forms of adrenal insufficiency, some untreated classic CAH patients seem to have less cli...

Background: Patients with Congenital Adrenal Hyperplasia (CAH) are at risk of several co-morbidities, such as impaired cognitive functions, short stature and adverse effects on metabolism. The causes of these effects are suboptimal glucocorticoid replacement therapy, adrenal crises and prenatal glucocorticoid exposure. However, there are no data available to this day how these factors are affecting epigenomic programs.Objective and hypot...

Background: Congenital adrenal hyperplasia (CAH) is a disease inherited by autosomal recessive manner and one of the most common congenital metabolic disorders. The incidence of CAH has been reported mainly through neonatal screening tests, mostly for 21-OHD. It is reported that 21-OHD occurs one in 15,000 people per year. However, there are few studies on all types of CAH incidence including 21-OHD. CAH is a rare disease, studies on large populations are needed to identify a ...

Introduction: An optimized replacement regimen with glucocorticoids and mineralocorticoids in subjects with congenital adrenal hyperplasia (CAH) aims at preventing life-threatening salt wasting and adrenal crises, virilization and pubertal precocity, and at enabling normal linear growth.Aims: We investigated puberty and its impact on final height in children and adolescents with CAH.Patients and Methods: In a cohort of post-pubesce...

Introduction: The Short Synacthen Test (SST) is the most popular diagnostic investigation of adrenal insufficiency (AI) amongst adult and paediatric endocrinologists. AI can present insidiously and symptoms may be non-specific. The number of medical indications for glucocorticoids is growing and SST usage is correspondingly increasing. There is evidence that an early morning plasma cortisol (EMC) of below ~100–150 nmol/l is highly predictive of failing the SST and the cor...

Background: Optimisation of hydrocortisone replacement therapy remains challenging due to complex pharmacokinetics as circulating cortisol is protein bound mainly to corticosteroid-binding globulin (CBG) that has a circadian rhythm.Objective: A detailed analysis of the CBG circadian rhythm and its impact on cortisol exposure during hydrocortisone replacement therapy.Methods: CBG was measured over 24 h in 14 healthy...

The amniotic fluid (AF) milieu is complex and essential to fetal well-being. Here we present a new LC-MS/MS method for the targeted metabolomics analysis of 20 unconjugated and conjugated steroids in 65 AF samples during mid-gestation. Sample preparation included protein precipitation, centrifugation, solid phase extraction and derivatization. We measured progesterone (Prog), 17α-hydroxyprogesterone (17OHProg), testosterone (T), estrone (E1), estradiol (E2), estriol (E3),...

Background: Adrenocortical Tumors (ACT) is a rare endocrine malignancy with heterogeneous presentation.Aim: To evaluate the clinical, biochemical and pathologic characteristics of pediatric ACT in a single tertiary center.Subjects and methods: Review of 28 medical records with childhood ACT (chronological age (CA) <18 years (y) treated between 1987 and 2017. Clinical, biochemical, and histological features (Wieneke index), stag...

Mast cells are known to control mineralocorticoid synthesis and secretion in human normal adrenal gland and aldosterone-producing adenomas through release of serotonin. We recently detected these immune cells in human fetal adrenal from 18 weeks of gestation in the subcapsular layer, in correlation with the expression of steroidogenic enzymes required for aldosterone biosynthesis. This observation suggests the implication of mast cells in the mineralocorticoid synthesizing pat...

The contiguous gene deletion syndrome, CAH-X, was reported in an 8.5% of Congenital Adrenal Hyperplasia (CAH) patients with a TNXA/TNXB chimera. This results in deletions of CYP21A2 gene, encoding 21-hydroxylase necessary for cortisol biosynthesis, and TNXB, encoding the extracellular matrix glycoprotein tenascin-X (TNX). There are three TNXA/TNXB chimeras (CH1, CH2, CH3) that differ in the junction site, resulting in TNXB haploinsu...

Background: The Low dose dexamethasone suppression test (LDDST) is an important investigation for suspected Cushing’s Syndrome (CS). The traditional definition of normal suppression of serum cortisol to ≤50 nmol/l during the LDDST (0.5 mg 6 hrly × 48 h) comes from a time when biochemical autoanalysers did not routinely detect very low values. Previous studies reported 5.1–8.3% of patients with Cushing’s Disease (CD) suppressed to <50 nmol/l at 48 ...

Objective: Congenital isolated ACTH deficiency (IAD) is a rare autosomal recessive disorder that is characterised by low levels of plasma ACTH and cortisol with normal pituitary structure and hormones. Clinical presentation can occur in the neonatal period, as well as later in childhood. Here, we report a patient with IAD due to a novel TPIT mutation.Case: A 48/12 years old girl presented with loss of concioussness and found to be hypoglycemic...

Background: P450 oxidoreductase (POR) mutations can present with disordered sexual development (46,XX virilisation as well as 46,XY under-masculinisation), perturbed steroidogenesis and mild to severe skeletal malformations. As POR is an obligate electron donating cofactor to many P450s, and as this interaction may vary from partner to partner, the phenotypic spectrum of PORD is extremely broad. Therefore, to characterize novel POR mutations, specific testing is required.<...

Context: The early activation of adrenal zona reticularis, denoted by increased circulating levels of adrenal androgens before the age of eight years in girls is called premature adrenarche (PA), while the concomitant appearance of pubic hair is termed premature pubarche (PP). Girls with PA-PP display an unfavorable metabolic, hormonal and psychologic profile, compared to their normal peers and are also at an increased risk of developing polycystic ovary syndrome (PCO...

Introduction: The low-dose synacthen test (LDT) is widely used to assess central adrenal insufficiency (CAI); however, the total serum cortisol (C) cut-off value is controversial. A correct diagnosis of CAI is required, but overdiagnosis may lead to unnecessary hormone replacement therapy. Salivary cortisol (SC) reflects the levels of free serum cortisol and is a noninvasive alternative.Objective: To define a new cut-off value of serum cortisol in pediat...

Background: Premature adrenarche (PA),characterized by high concentrations of DHEAS,has been considered a benign condition until recently,where associations to increased metabolic risk and PCOS have arisen,which may depend on ethnic background and infancy weight gain.Objective and hypotheses: To determine whether PA in girls determines:i)a different timing of pubertal events, and ii)a different pattern of Ovarian morphology/hormones and adrenal hormones....

Objective: To evaluate the impact of gestational age and birthweight on dehydroepiandrosterone and dehydroepiandrosterone-sulfate (DHEA and DHEA-S) in children born very preterm (VPT) appropriate for gestational age (GA) compared to children born at term (T).Methods: We recorded anthropometric parameters in 72 VPT (<32 GA) and 41 T (≥ 38 GA) aged 5.0–8.5 years. Birthweight standard deviation scores (BW-SDS) were calculated using INTERGROWT...

Background: PHA1 is a rare inherited disease characterized by resistance to aldosterone action and distinguished in two forms: the autosomal dominant renal form caused by mutations of the NR3C2 gene (MR) and the autosomal recessive systemic form caused by mutations of the subunit genes SCNN1A, SCNN1B, SCNN1G of the epithelial sodium channel (ENaC). The classic phenotype of the autosomal recessive form of PHA1 is usually severe, lifelong, and expressed with mu...

Introduction: Maternal perinatal mental disorders (PMDs) are associated with developmental and behavioral problems in the offspring, probably mediated by the programming of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis. Increased or decreased cortisol concentrations during pregnancy and the perinatal period have been associated with alterations in the stress responses of the offspring and with child behavioral problems; however, such associations remain unclear.<p ...

Background: In pediatric patients with adrenocortical tumors (ACT), morbidity and mortality rates have been extensively evaluated. However, there are almost no data on the late consequences of early exposure to high androgen levels on pubertal development and on final height (FH) in these patients.Objective: To investigate the impact of early exposure to androgen excess on gonadotropin-dependent pubertal development and on final height (...