ESPE Abstracts

Background: DAVID syndrome (deficit in anterior pituitary function and variable immune deficiency) (J Clin Endocrinol Metab 97 E121, 2012) can be caused by NFKB2 mutations (Am J Hum Genet 93 13, 2013). All patients have an orthotopic posterior pituitary (PP) and most only ACTH deficiency.Objective and Hypothesis: To describe a girl with common variable immunodeficiency (CVID), ectopic PP (EPP) ...

Background: In children undergoing investigation of testicular function the relationship between serum anti-Mullerian hormone (AMH) and the testosterone response to hCG stimulation test (HST) is unclear.Method: 75 children (3F, 72M) with a median age of 1.08 years (range, 0.003, 14.3) were investigated for suspected DSD by AMH on D1 and testosterone on D1 and D4, before and after 3-day HST. Of these children, 27 had an additional prolonged HST. Normal te...

Background: Calculation of a urinary steroid metabolite ratio (uSMR) may be a useful method of improving diagnostic yield when investigating disorders of steroid hormone synthesis. Our aim was to investigate the range of uSMR in children with suspected disorders of steroid hormone synthesis.Methods: Ten ratios were calculated on steroid metabolite data analysed by GC-MS in urine samples collected between 2008 and 2010 from 94 children who were undergoing...

Background: GH insensitivity (GHI) encompasses growth failure, low serum IGF-1 and normal/elevated serum growth hormone (GH) (basal level >5 μg/L and/or peak on provocation testing >10 μg/L). In a significant number of children the molecular cause is unknown.Objective: To investigate the genetic etiology of GHI in a cohort of children by candidate gene (CGS) and whole exome (WES) sequencing.Methods: About 109 pati...

Background: Children born small for gestational age (SGA) are at increased risk of coronary heart disease and type 2 diabetes in adulthood, due to reprogramming of endocrine and metabolic functions. Dysregulation of specific miRNAs in response to genetic and environmental factors contribute to aberrant gene expression patterns underlying metabolic dysfunction.Objective and hypotheses: We aimed to identify miRNAs associated with increased risk of obesity ...

Background: Germline mutations in SDHB gene are associated with the familial paraganglioma (PGL) syndrome that carries the highest malignant potential. Although penetrance is lower than initially described, lack of effective treatments for metastatic PGLs makes screening essential for early tumour detection, surgical removal and improved outcome. However, no consensus exists in relation to timing and mode of screening.Objective: To assess publis...

Background: Noonan syndrome (NS) is caused by variants in multiple genes regulating the RAS/MAPK signalling cascade. NS can present with growth failure associated with growth hormone insensitivity (GHI; low IGF-I and normal/elevated GH levels). Variants in LZTR1 lead to NS, although the interaction of LZTR1 with the RAS/MAPK and the GH-IGF-1 pathways remain to be elucidated.Objectives: To gain insights into the ...

Among the many complications of type 1 diabetes (T1D), hypoglycemia is an acute concern for children with T1D and their families. Moreover, fear of hypoglycemia is a common barrier to achieving glucose targets. Numerous advances in care have been made since the Diabetes Control and Complications Trial was published in 1993 in which lower HbA1c was associated with increasing risk of severe hypoglycemia. More recent data indicate that lower HbA1c (7% ISPAD target) can be ach...

Glucocorticoids (cortisol in humans, corticosterone in rodents) are critical regulators of energy metabolism and immunity. Their secretion by the adrenal gland follows a circadian pattern, with serum concentrations peaking before the active phase (day in humans, night in rodents). Synthetic glucocorticoids are the most potent anti-inflammatory agents known, and are widely used therapeutically, with >1% of the UK population holding a prescription long-term. However, frequen...

Background: The arrangement of beta cells within islets of Langerhans produces a gain-of-function in insulin release through the generation of rhythmic activity patterns. A privileged role for individual beta cells in orchestrating these responses has long-been suspected, but not directly examined.Objective and hypotheses: Identify and characterize a rare subpopulation of beta cells tasked with pacemaking insulin release.Method: Op...