Endocrine Abstracts

Aim: The aim of investigation to determine clinical aggressiveness diagnostic markers in patients with non-functional pituitary adenomas (NFPA), and growth hormone deficiency (GHD) in the formation of gravity neuroendocrine disease symptoms.Material and methods: We observed in 87 patients (including man – 44 women – 43) of which have a verified diagnosis of NFPA after surgery – 31 which were subjected transnasal adenomectomy of the pituiat...

Introduction: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 15–30% of familial isolated pituitary adenomas (FIPA). We report a 4-generation FIPA kindred with a heterozygous AIP gene deletion in exon 2, highlighting the benefits of genetic screening and management challenges in affected subjects and asymptomatic carriers.Patients: A 45y woman died of a spinal ependymoma (obligate carrier)...

Introduction: Metformin is used as a first line treatment in type 2 diabetes. Several studies suggest that patients with type 2 diabetes treated with metformin may have reduced cancer risk. Recently it has been shown that Metformin acts directly on mitochondria to alter cellular bioenergetics and reduce tumorigenesis. We have shown that anti-proliferative effect of Mitotane is related with changes of expression of the genes involved in mitochondrial metabolism in human adrenoc...

Introduction: Tumours with aryl hydrocarbon receptor interacting (AIP) mutations often show an unusually aggressive and invasive clinical course as up to 80% of AIP positive pituitary adenomas have a certain degree of extrasellar extension. The exact mechanisms by which AIP inactivation promotes an aggressive behaviour remain unknown. The majority of adenohypophysis is composed of sinuous cords of epithelial cells and consequently, molecules that can induce remodellin...

Introduction: Mutations in the aryl hydrocarbon receptor-interaction protein (AIP) gene predisposes to growth hormone or prolactin secretin adenomas, usually, manifesting before the age of 30 years old. There are 834 variants of the AIP reported in the GnomAD database and over 100 variants have been described in patients with pituitary adenomas. While the pathogenic role of variants resulting in truncated protein is beyond doubt, determination of the clinical...

Introduction: Acromegaly is a neuroendocrine disorder caused by excessive secretion of growth hormone (GH). Current treatment includes surgery, radiotherapy and drugs like somatostatin or dopamine receptor agonist. In spite of combination of therapies cure rate is dismal. There is a quest for new therapeutic targets with optimal efficacy, least side effect without any cost constraints. Recently, a few reports have shown that tyrosine kinase inhibitor (Imatinib) causes growth f...

Background: Pituitary apoplexy (PitApo) has significant associated-morbidity and its management is not yet standardised.Aim: To describe prevalence and characteristics of PitApo patients in GH deficient (GHD) patients compared with two control populations.Patients and methods: Patients with ‘infarction-apoplexy’ GHD aetiology code were identified from Pfizer International Metabolic Database (KIMS). Baseline characteristic...

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...

Locus-specific databases (LSDBs) have been recently developed in response to the increasing number of genetic changes reported in the human genome. LSDBs have been created for several genes implicated in endocrine syndromes, for example MEN1, VHL, RET, GNAS, PRKAR1A and the SDH subunits. Mutations in AIP are found in about 20% of familial isolated pituitary adenoma (FIPA) patients.The aim of this proj...

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...