Endocrine Abstracts

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...

Background: No predictive biomarkers have been identified for clinically nonfunctioning pituitary tumour (NFPT) recurrence, with Ki67 being controversial. We employed quantitative mass spectrometry-based analyses to examine the differential expression of proteins in NFPTs.Methods: NFPTs were sub-grouped: non-invasive/non-recurrent group (NI/NR-G, n=5), invasive group (I-G, n=10) and recurrent group (R-G, n=5). Invasiveness was ...

Background: The cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) signalling pathway is an element of the innate immune response and is activated by the presence of DNA in the cytosol. Triggering of this immune response may occur in the setting of infection or neoplasia. Activation of this pathway results in phosphorylation of interferon regulatory factor 3 and downstream transcription of cytokines such as interferon β and interleukin-6. Polyinosinic:pol...

Introduction: Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHOA) is a rare genetic condition characterised by digital clubbing, pachydermia, hyperhidrosis, cutis verticis gyrata and periostosis. The SLCO2A1 transporter and HPGD enzyme genes play an important role in prostaglandin metabolism, hence loss of function mutations in them causes PHOA. To date, according to the VarSome database 101 and 41 variants have been identified in the SLCO...

Introduction: AIP mutations are responsible for 15-30% of cases of familial isolated pituitary adenomas. The pathophysiology that drives this AIP-related pituitary tumorigenesis is not fully understood. We developed a pituitary-specific Aip knockout (KO) mouse model, which mostly recapitulates the human phenotype.Aims: To performed comparative gene expression analysis of Aip-KO mouse pituitary tumours and AIP mutation positive ...

Introduction: Tumour microenvironment (TME) is determined by non-tumoral cells, including immune, stromal or endothelial cells, and influences tumorigenesis, proliferation, invasiveness and angiogenesis. Little is known about TME in pituitary adenomas (PAs). We aimed to characterise the TME of PAs and its role in their aggressiveness, focusing on PA-infiltrating immune cells and cytokine network.Methods: Cytokine secretome from 24 human PAs (16NFPAs, 8GH...

Background and aim: Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionary conserved and widely distributed throughout organism. Broad interest for AIP comes from involvement of loss-of-function AIP mutations in pituitary adenoma pathogenesis. The role of AIP in normal pituitary function is largely unknown. AIP is co-localized with GH in somatotroph secretory vesicles. Serum AIP protein was proteomically identified. We aimed at investigating whether AIP and GH are...

40-year-old female patient presented with acromegaly in 2008 (GH 61 (g/L, IGF-1 774 ng/ml PRL 1500 mU/L). Macro-adenoma invading the right cavernous sinus was found on MRI and she underwent two pituitary surgeries revealing sparsely granulated GH adenoma with scattered PRL cells, low Ki 67 and negative p53 immuno-staining. Her second cousin was treated for macro prolactinoma. Both patients tested negative for germline mutations in the AIP and menin genes. Treatment with somato...

Case history: A 63-year-old female presented with bi-temporal hemianopia. Pituitary MRI demonstrated a macroadenoma with suprasellar extension. Her medical history included a glomus tumour of the right ear treated with external beam radiotherapy (EBRT) 25 years previously. She had no evidence of pituitary hormone abnormality and had normal urinary metanephrines levels. She underwent transsphenoidal surgery with total resection and full recovery of her visual fields. Immunohist...

Introduction: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options. Mitotane is considered as a first-line therapy but only 30% of the patients showing an objective tumour response.Erlotinib and gefitinib (tyrosine kinase inhibitors – TKI) inhibit the epidermal growth factor receptor (EGFR), which is highly expressed and occasionally mutated in various cancers. EGFR expression was found to be a good ...