ESPE Abstracts

The McCune–Albright syndrome can be a disease of striking complexity, the management of which can be challenging. However, an understanding of the physiologic consequences of the underlying molecular and developmental biology makes the evaluation and treatment of this disease relatively straightforward. MAS arises from activating mutations in the ubiquitously expressed cAMP-signaling protein, Gsα. The mutations occur very early in development, prior to gas...

Osteoclasts are bone-resorbing cells important in normal growth plate development and bone remodeling. The development of osteoclasts is potently driven by mononuclear RANK and osteogenic cell RANKL interaction. Denosumab is a monoclonal antibody drug that targets RANKL and inhibits osteoclastogenesis. It is a potent and effective treatment for pathologic processes that involve bone resorption, such as osteoporosis and bone metastases, conditions for which it is approved. Deno...

Background: Many children with short stature (defined as height SDS <−2S.D.) have no identified cause for their growth impairment and are classified as either small for gestational age or idiopathic short stature depending on birth size. Whole exome sequencing (WES) is a useful tool to identify new genetic diagnoses in this group. Here we describe a recurrent NDUFB3 mutation in children with intra-uterine growth retardation, short stature and ...

Background: The need to understand the relationship between bone, muscle, and fat within the bone-muscle unit has recently gained great prominence. Although high resolution (HR) MRI is a non-invasive imaging modality that can provide this information, there is limited expertise in children and young people.Objectives: To establish MRI-based normative data for bone, bone marrow adiposity and muscle adiposity in children a...

Abnormal DNA methylation contributes to tumor progression and is emerging as a prognostic marker in several types of cancers. To investigate whether DNA methylation is associated with pediatric adrenocortical tumor (pACT) presentation and patient prognosis, we analyzed the methylation profile of 57 tumors (MethylationEPIC BeadChip Array-Illumina) and patients’ clinicopathological features and outcome. The study comprehended 40 girls and 17 boys, with median age at diagnos...

Background: It is well known that growth hormone (GH) brings about several effects, involving bone, body composition, lipids and glucose homeostasis. However, the complex interplay between these parameters is rather poorly studied in children with childhood-onset-GH deficiency (CO-GHD).Objective and hypotheses: To investigate lipids, adipokines (leptin- adiponectin- resistin) and glucose homeostasis and their relationship with bone and body composition i...

Synacthen tests are used widely in paediatric practice for diagnosis of AI. The standard dose test may be more specific and low dose test (LDSST), more sensitive. The LDSST requires dilution of commercially available Synacthen, which may result in unreliable dosing and over diagnosis of AI.Aim: To determine the prevalence of AI requiring treatment with hydrocortisone (a) daily (peak cortisol <350nmol/l) (b) on sick days only (peak co...

Catch-up growth (CUG) is characterized by a period of supranormal height velocity following a transient period of growth inhibition. The two classical hypotheses on the mechanism are the neuro-endocrine hypothesis (a central mechanism that would recognize the degree of mismatch between actual size and target size) and the growth plate hypothesis (local regulation of growth according to a preset cellular program of senescence, characterized by decreasing growth proliferation ra...

Study of the histopathology of human type 1 and 2 diabetes through the national pancreatic organ donor (nPOD) consortium has yielded interesting new insights that should also aid us in developing improved therapeutic approaches.1. When insulitis is observed, it usually shows a predominance of CD8 T cells, some of which are autoantigen specific (see also Coppieters et al. JEM 2012). It will be therapeutically challenging to remove/prevent CD8 mem...

Background: Cardiovascular disease (CVD) is the major cause of mortality in diabetes mellitus type 1 (T1DM). Dyslipidemia will increase this risk. Several guidelines have been published, how to treat dyslipidemia in T1DM, yet some studies have shown that the number of patients who are treated according to these guidelines is low.Objective and hypotheses: To investigate the frequency of dyslipidemia in children and adolescents with T1DM and if they are tr...