Endocrine Abstracts

Neuroendocrine tumours (NETs) occur in multiple sites including, the pancreas, gastrointestinal tract, lung, thymus, parathyroid, adrenals and pituitary. Current treatments for advanced NETs such as surgery, chemotherapy or radiotherapy, rarely achieve a cure due to metastases at presentation therefore additional therapeutic treatments are required. Identification of cell surface receptors or binding sites that are unique or up-regulated on tumour or neuroendocrine tissue coul...

Introduction: Loss-of-function mutations in AIP are associated with familial isolated pituitary adenoma, often leading to gigantism due to invasive GH-secreting pituitary adenomas. One challenging problem in the management of patients carrying a missense AIP variant is to determine whether the missense variant is a disease-causing mutation or not. As most of the molecular mechanisms involved in the control of growth and the cell cycle are well-conserved, we p...

Background: It is often difficult to define the clinical relevance of a novel gene variant. In silico analyses of variants located close to exon–intron-junctions are utilised to predict the result of these basepair changes. We have previously identified two splice-site variants in AIP and confirmed the predicted changes for c.249G>T, p.G83AfsX15 and c.807C>T. We identified the c.469-2A>G heterozygous variant located at the end of intron-3 in a childhood...

Introduction: 131I-MIBG is a well-established treatment modality for patients with neuroendocrine tumours (NETs). Our centre has now accumulated over 10 years of experience with 131I-MIBG therapy, with long term data to evaluate effects on disease progress and other long term outcomes following therapy. Bone marrow effects of radionuclide therapy may include prolonged suppression, myelodysplasia or even frank leukaemia. Incidence is thought to be low, but...

Background: 20% of the familial isolated pituitary adenoma (FIPA) population harbour an aryl hydrocarbon receptor-interacting protein (AIP) gene mutation. The recognition of whether a variant is pathogenic can be difficult, in cases where the observed change does not lead to a truncated protein. Segregation with disease in a family, in silico predictions, loss of heterozigosity in the tumour, in vitro functional studies and screening of the variant in controls may help in asce...

Introduction: Bone mineral density (BMD) and fracture tendency are influenced by diet, activity, drugs, and hormones. Recent studies highlight an inverse relationship between serotonin and BMD, of uncertain mechanism.Purpose: We investigated the relationship between serotonin metabolites and BMD in patients with sporadic neuroendocrine tumours (NETs), with and without the carcinoid syndrome.Materials and methods: One-year prospecti...

Background: Somatostatin analogues are very useful in the treatment of symptomatic neuroendocrine tumours, but effects on proliferation remain unclear. Overexpression of the proto-oncogene protein kinase Akt has been demonstrated in certain endocrine tumours, and activates downstream proteins including mTOR and p70S6K, which play a significant role in cell growth and proliferation. We have therefore explored the site of action of somatostatin in causing inhibition of prolifera...

Background: Cushing’s syndrome results from chronic exposure to excessive levels of glucocorticoids (GC). The clinical manifestations associated with hypercortisolaemia are variable and differ widely in severity, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to changes similar to the metabolic syndrome. We hypothesised that GC might influence the expression of the genes involved in lipogenesis and gl...

Background/objective: Published data suggest that growth hormone replacement (GHR) may be safely given to patients with hypopituitarism consequent upon a pituitary/peri-pituitary tumour. However, to date, these series have included a preponderance of patients treated with external pituitary irradiation. We have performed a retrospective study to evaluate the recurrence rate in a group of patients with pituitary/peripituitary tumours treated with GHR.Meth...

Background: Ghrelin was recently discovered as the natural ligand for the G protein-coupled growth hormone secretagogue receptor and induces GH release through GHS-R1a. The octanoylation of its third serine residue is responsible for GH release and receptor binding. A variant of ghrelin devoid of this modification, desoctanoyl-ghrelin, can neither bind to the receptor nor induce GH release. Ghrelin has also been shown to effect cellular proliferation, being pro-proliferative i...