Endocrine Abstracts

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: 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...

Aryl hydrocarbon receptor-interacting protein (AIP) is a highly expressed, evolutionary conserved little-known co-chaperone molecule that can bind to client proteins. Heterozygous loss-of-function mutations of AIP are associated with pituitary adenomas. Multiple lines of evidence suggest that AIP has important functions beyond the pituitary gland. Homozygous loss of AIP is lethal, with cardiac abnormalities seen in mice and failure-to-thrive seen in fruit flies and C.elegans. ...

Background: No predictive biomarkers for NFPT recurrence have been identified, apart from Ki67. We employed high-throughput mass spectrometry-based analyses to examine the phosphorylation pattern of different subsets of NFPTs. Methods: Based on histopathological, radiological and surgical features, NFPTs were sub-grouped into three groups: non-invasive (n = 15), invasive (n = 10) and recurrent (n = 5) subtypes. Invasiveness was...

Introduction: Patients with a germline loss-of-function mutation in AIP are predisposed to young-onset GH excess resulting in gigantism or acromegaly. Acromegaly leads to disease-specific cardiomyopathy with biventricular hypertrophy and diastolic dysfunction progressing to fulminant cardiac failure if left untreated, therefore it is vital to have a tractable animal model to investigate the diseaseFindings: Our AipFlox/Flox;<...

Introduction: Hormone macromolecules are complexes of hormones with other compounds, most often with IgG immunoglobulin. They show variable immunoreactivity in immunochemical tests (IRMA, ELISA, CLIA, ECLIA) and usually have a weak biological effect. They can interfere with immunological assays of various hormones. Some known hormone macrocomplexes are: BB-PRL (24% - 34%), macro-TSH (0.6% - 1.2%) and very rare macromolecules of various hormones: calcitonin, PTH, insulin (singl...

Introduction: The tumour microenvironment significantly influences tumour behaviour. Little is known about the pituitary adenoma microenvironment. AIP mutation positive (AIPpos) patients develop often aggressively growing pituitary tumours and the study of their microenvironment might identify factors leading to this aggressive phenotype which could help predict tumour behaviour and identify novel therapeutic targets.</p...