Endocrine Abstracts

Background: PTEN hamartoma tumour syndrome (PHTS) is a rare autosomal dominant disorder characterised by macrocephaly and multiple hamartomas. It carries an increased risk of several cancers, including breast, thyroid and endometrium. PHTS is caused by inactivating mutations of PTEN (phosphate and tensin homologue deleted on chromosome 10), which encodes a tumour suppressor phosphatase. Published guidelines for surveillance are available for adult patients but not adv...

Background: PTEN hamartoma tumour syndromes (PHTS) are rare autosomal dominant inherited disorders characterised by macrocephaly, multiple hamartomas and an increased risk of several cancers, including breast, thyroid and endometrium. PTEN encodes a tumour suppressor phosphatase that regulates cell survival and migration. Published guidelines are available for adult patients but screening in children is currently not standardised. Moreover, there is poor genotype-phenotype cor...

Introduction: The debate surrounding the most suitable pituitary provocation test in children is controversial. There is a perception that the gold standard insulin tolerance test (ITT) is ‘dangerous’ and that the glucagon stimulation test (GST) is ‘safer’ and a more tolerable alternative, particularly in younger children. There have been no reports in the literature comparing patient experiences of these tests.Aim: To examine the tol...

Over 700 patients with known adrenal insufficiency are treated across the trust. Whilst unwell or fasting for a procedure, these patients potentially risk suffering an adrenal crisis. A flagging system has already been implemented on the electronic patient records (EPR) which identifies patients who are ‘on replacement Hydrocortisone’. Following an inpatient adrenal crisis which could have been more optimally managed, we sought to highlight care of this vulnerable co...

Background: Recombinant human Insulin-like growth factor-1 (rhIGF-1) is the only treatment for short stature due to primary IGF-1 deficiency and related disorders. However, treatment needs meticulous monitoring for adverse effects, especially hypoglycemia, obstructive sleep apnoea (OSA), raised intracranial hypertension, cardiac complications and skin reactions.Method: To determine therapeutic potential, efficacy and safety of rhIGF-1 treatment, case not...

Introduction: Hypercalcaemia secondary to malignancy is rare in childhood. Bisphosphonates have previously been shown to be effective in managing such cases in adults, however caution must be exercised in patients with renal failure or respiratory compromise. Denosumab, a RANKL monoclonal antibody is a very potent inhibitor of osteoclasts and can induce hypocalcaemia. It is not excreted by the kidney. Limited trials in adults have shown denosumab to have greater efficacy compa...

Background: The standard synacthen test (SST) is commonly utilised to interrogate the hypothalamo-pituitary-adrenal (HPA) axis in children. It comprises baseline and 30-minute serum cortisol concentrations (SCC), after injecting synthetic adrenocorticotropic hormone (ACTH)[1–24]. There is debate regarding the utility of a 60-minute SCC in the SST protocol with most studies to date conducted in adults.Aim: To assess the utility of a 60-minute SCC in ...

Introduction: The UK 100,000 Genomes Project (100KGP) investigated the genetic basis of rare disease. The molecular drivers of most paediatric pituitary disease remains unknown.Methods: Children with genetically unexplained pituitary disorders attending a tertiary paediatric endocrinology centre were recruited to the 100KGP and underwent whole genome sequencing. Parental DNA was obtained where feasible. Virtual gene panels were applied and bioinformatic ...

Background: Delta-like homologue 1 (DLK1) encodes a transmembrane protein, which may also be secreted into the circulation. Levels are known to rise in maternal serum during late gestation and our genetic studies in the mouse have shown that this DLK1 arises from the conceptus. The cell population that secretes DLK1 into the maternal circulation has not been identified. In humans DLK1 has been shown to be differentially expressed in intrauterine growth restricted (IUGR) when c...

Introduction: The Sonic hedgehog (Shh) pathway is an evolutionarily conserved signalling pathway, playing an essential role during embryonic development. Murine studies have shown the importance of Shh in the growth of the adrenocortical primordium. Shh expression has previously been described in relatively undifferentiated sub-capsular cells in the developing rodent adrenal, however the organisation of the human foetal adrenal (HFA) is unique. This novel study aimed to descri...