ESPE Abstracts

Background: Dominant mutations in ABCC8 can cause congenital hyperinsulinism (CHI), which is characterised by unregulated insulin secretion.Objective and hypotheses: To understand the molecular basis of medically unresponsive CHI due to dominant ABCC8 mutations.Method: We investigated ten patients with diazoxide unresponsive CHI who required a near total pancreatectomy. DNA sequencing revealed seven dominant heter...

Background: Growth retardation affects more than 80% of patients with Noonan syndrome (NS; MIM#163950), one of the most common developmental disorders, but its origin remains poorly understood. We have demonstrated that mutations of the tyrosine phosphatase SHP2, that are responsible for half the cases of NS, impair the systemic production of Insulin-like growth factor 1 (IGF1), the biological mediator of GH acting on growth plate, through a hyperactivation of the Ras/Mitogen-...

Objectives: GH deficiency (GHD) and small for gestational age (SGA) status are associated with cardiovascular risks. We therefore investigated antiatherogenic effects of GH.Methods: Subfractions of LDL and HDL, lipoprotein-associated phospholipase A2 (Lp-PLA2), and high-sensitivity C-reactive protein (hsCRP) were measured at baseline, after 8 and 52 weeks of GH treatment in 51 short children born SGA (n=33) or with GHD (n=18).<p cla...

Background: Leydig-cell tumours in children are rare, comprising only 4 to 9% of all primary testis tumours in prepubertal males. These boys present with isosexual precocious pseudopuberty characterized by increased testosterone and low gonadotropin levels. We describe two cases and will discuss differential diagnosis and pathogenesis.Case 1: C. was first referred at 8 years old for pubertal development with accelerated growth since 4 years of age. His v...

Background: Pituitary stalk interruption syndrome (PSIS) is a frequent cause of congenital hypopituitarism. Patients are initially referred for the evaluation of hypoglycemia during the neonatal period or growth retardation during infancy or childhood. PSIS are either associated with extra-pituitary malformations (EPM+) or isolated (EPM−).Objective and hypotheses: To compare baseline characteristics, GH response, and long term evolution in patients...

Background: Genetic defects in the Wnt signaling pathway lead to early-onset osteoporosis (EOOP). Romosozumab is a monoclonal antibody against sclerostin, an inhibitor of the Wnt/ß-catenin pathway. Romosozumab has shown great efficacy in adult osteoporosis, however its effect in patients with Wnt-related EOOP is unknown. In monoallelic loss-of-function WNT1 mutations, romosozumab could potentially stimulate the defective Wnt signaling pathway an...

Background: Children with biallelic GHRHR gene pathogenic variants share a phenotype of growth failure starting in infancy and resulting in a proportionate short stature and bone age delay due to a complete isolated growth hormone (GH) deficiency. The genotype ranges from rare promotor mutations to the more frequent splicing mutations, some genotypes being specific to certain geographic areas. Diagnosis is mainly made around the age of 7 years and more often i...

Background: Hypercalcaemia has various etiologies and treatment is often challenging. Therapeutic options include aggressive fluid management, loop diuretics and antiresorptive drugs. Since both hypercalcaemia and bisphosphonates can cause acute kidney injury (AKI), bisphosphonates are not recommended in patients with renal impairment. Denosumab, an antiresorptive human monoclonal antibody, is not associated with AKI and offers a temporary treatment option. Ho...

Background: Congenital Hypothyroidism (CH) is the most common neonatal endocrinologic disorder and one of the most preventable causes of mental retardation and neurological alterations in children. The incidence of CH lies between 1 in 2000-3000 newborns. The replacement therapy with levothyroxine (LT4) should be started immediately since studies show that a rapid normalization of TSH and fT4 optimizes the neurodevelopmental outcome. Infants with Down syndrome...

Background: COVID19 Lockdown resulted in an extreme change in daily lifestyle with a significant increase in weight and loss of quality of life, as well as an increase in the risk of secondary health conditions even in young people. One reason for this is a fatal change in the nutritional situation, especially among adolescents. Convincing models to counter this problem are missing so far. Multiprofessional training programs could reveal an outstanding effect ...