Endocrine Abstracts

Introduction: Loss of function mutations in SGPL1, a key component of sphingolipid metabolism, are associated with accumulation of sphingolipid intermediates giving rise to a multisystemic disease incorporating primary adrenal insufficiency (PAI) and progressive renal and neurological disease. Sphingolipid accumulation is implicated in mitochondrial pathology.Objective: To investigate the impact of SGPL1 deficiency on mitochondrial morphology/ f...

Introduction: The management of type 1 diabetes (T1D) in young children can be extremely challenging due to high insulin sensitivity, unpredictable eating and activity and difficulty recognizing symptoms of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) therapy is beneficial in managing young children, however the small insulin doses required challenge the accuracy of standard concentration (100 IU/ml) CSII.Case report and literature revi...

Small cell lung cancer (SCLC) is distinguished by its neuroendocrine phenotype and secretion of hormone biomarkers. Tumours initially respond well to therapy but almost invariably relapse with a therapy-resistant phenotype. We have previously described pro-opiomelanocortin (POMC) as a potential biomarker of SCLC. In this study, we investigated how POMC acts as a biomarker of tumour response to treatment.SCLC cells (DMS 79) were injected subcutaneously in...

Acromegaly causes impaired insulin sensitivity and reduced fat mass. Using acipimox to block lipolysis, the impact of free fatty acids (FFA) on insulin sensitivity in active acromegaly was investigated. 1H MRS was used to quantify triglyceride (TG) content of liver and muscle.Methods: 6 patients with active acromegaly (AA) (5M, age 59 (34–70), IGF-I (ng/ml) (median (range)) (452 (342–1002)) were studied on 2 visits; (i) baseline (BL)...

Objective: Aldosterone-producing adenomas (APA) are a major cause of primary aldosteronism. Somatic mutations explain the excess aldosterone production in the majority of patients with APA with mutations in KCNJ5 encoding a potassium channel the most prevalent in most reported populations. Mechanisms driving cell proliferation are largely undefined.Design and method: Quantitative transcriptome analysis using RNA-seq was used to identify differen...

Articular cartilage maintenance and repair is regulated by numerous endocrine and paracrine factors. Investigation of molecular mechanisms underlying osteoarthritis (OA) is limited by inability to identify early stage disease and individuals at risk of progression. Susceptibility to OA is genetically determined and the availability of mice from the International Knockout Mouse Consortium with deletions of every known gene provides a unique opportunity to investigate its pathop...

Visinin-like 1 (VSNL1) is upregulated in aldosterone-producing adenomas (APA) compared to normal adrenals. We demonstrate that VSNL1 overexpression in adrenocortical carcinoma cells (NCI H295R) upregulates basal and angiotensin II (Ang II)-stimulated CYP11B2 gene expression 3.2- and 1.5-fold, respectively. Conversely, silencing VSNL1 by RNA interference decreases Ang II-stimulated CYP11B2 expression and aldosterone secretion by 41 and 34.5%, respectively. Mutations in the pota...

Background: GH replacement during the childhood-adult transition period is important for somatic maturation. The aim of the study was to explore the factors influencing IGF1 response to GH during transition.Methods: KIMS (Pfizer International Metabolic Study) database in UK was interrogated, and 98 patients (55 male, median age 20.7 years (15.7–25.8)) with childhood-onset GH deficiency (Co-GHD), who were started on adult dose of GH during transition...

20% of cases of FIPA have AIP gene mutations. These adenomas are often large and invasive. Our index case presented aged 13 with pituitary apoplexy. Histology showed necrotic tissue. He continued to grow and was 195 cm 4 y later. GH excess was confirmed. After treatment with octreotide and radiotherapy remission was achieved. His first cousin had also been successfully treated for acromegaly. This led to the original familial diagnosis. Subsequently, the c.910C>T, p.R304X ...

Background: GH therapy during the transition period is important for somatic maturation. Identification of factors associated with low IGF-I levels may be useful in optimising GH replacement therapy.Objectives: To explore the prevalence and determinants of insufficient GH replacement during transitionMethods: Childhood-onset GH deficient (CO-GHD) patients (n=65) who stopped therapy, and were started on adult GH dose during t...