ESPE Abstracts

Background: The underlying pathogenic mechanisms governing growth restriction of Noonan syndrome (NS) remain elusive. Monoallelic inactivating LZTR1 gene variants have been implicated as a cause of NS due to hyperactivation of the canonical RAS-MAPK signalling pathway. Missense LZTR1 variants have been associated with defective ubiquitination theoretically leading to increased Ras substrate availability. Ubiquitination is implicated in growth...

Pseudohypoparathyroidism (PHP) and related disorders lead to a wide spectrum of abnormal physical characteristics, neurocognitive and endocrine abnormalities. PHP (including all subtypes), pseudoPHP, acrodysostosis and progressive osseous heteroplasia refer to heterogeneous disorders characterized by physical findings, differently associated in each subtype, including short bones, short stature, stocky build, subcutaneous ectopic ossifications, as well as laboratory abnormalit...

Background: Down Syndrome (DS) patients have a higher incidence of primary hypothyroidism. We previously demonstrated that transgenic mice overexpressing Dyrk1A had developmental (larger primary thyroids at E15.5 stage of development), morphological (disorganized follicles) and functional (significant lower plasma T4) impairments similar to DS thyroidal impairments (Endocrinology 2015). DYRK1A, localized in the DS critical region on chromosome 21, is therefore the can...

Objectives: Hypophosphatasia (HP) is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity. The symptoms are highly variable in their clinical expression, which ranges from stillbirth without a mineralized bone to early loss of teeth without bone symptoms. We aimed to report a patient with HP presenting with fibrous dysplasia.Methods:</st...

Background and objective: Given phenotype variability as well as limited utility of conventional endocrine investigations in reaching the diagnosis in a 46,XY patient suspected of a disorder of sex development (DSD), there is an increasingly stronger argument for considering targeted genetic sequencing at an earlier stage of the evaluation process. This study focused on identifying the relationship between clinical examination, endocrine and radiological assessment, as well as...

Background: Next-generation sequencing (NGS) technologies have improved our knowledge about the genetic basis of congenital hypothyroidism (CH). The objective of our study was to evaluate the molecular genetic etiology in our primary CH cohort by using the NGS-based panel.Subjects and Methods: The clinical and genetic characteristics of 147 patients (61 female) from 129 unrelated families were evaluated. The patients wer...

Introduction: Worldwide the Short Synacthen Test (SST) is the most popular diagnostic investigation for adrenal insufficiency (AI) amongst both paediatric and adult endocrinologists. Cannulation and blood sampling are required making it invasive, time-consuming and resource-intensive. We have previously validated a reliably absorbed and well tolerated formulation of nasal synacthen (Nasacthin003) in healthy adult males, measuring the glucocorticoid response in salivary cortiso...

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and one of the most common preventable cause of intellectual disability in the world. CH may be due to developmental or functional thyroid defects (primary or peripheral CH) or be hypothalamo-pituitary in origin (central CH). In most cases, primary CH is caused by a developmental malformation of the gland (thyroid dysgenesis, TD) or by a defect in thyroid hormones synthesis (dyshormonogenesis, DH). T...

Osteogenesis imperfecta (OI) is a rare genetic disease characterized by bone fragility and an increased risk of fractures. Intravenous bisphosphonates are the current gold standard for the treatment of OI: the aim of this therapy is an increase in Bone Mass Density (BMD) and a consequent reduction in pathological fracture rates. Currently, the only bisphosphonate approved in Italy for pediatric population is neridronate, infused in hospital once every four months. In San Raffa...

Introduction: Autoimmune Polyglandular Syndrome Type I (APS1) is a rare condition caused by mutations in the AIRE gene (autoimmune regulator). The diagnosis is challenging and delayed due to its non-specific clinical manifestations such as candidiasis, hypoparathyroidism and hypoadrenalism. More than a hundred mutations of this gene have been described and hereby we present a girl who was found to have a novel mutation of AIRE gene with patho...