Endocrine Abstracts

Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 30% of pituitary gigantism cases. However, pathological accelerated growth and/or tall stature can be unrelated to the growth hormone (GH) axis, and may occur in isolation or as part of a syndrome, such as in Klinefelter, Marfan or Sotos syndromes. We report a five-generation kindred with two brothers with pituitary gigantism due to AIP mutation-positive GH-secreting pi...

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: 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...

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...

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...

Introduction: Angiogenesis is regulated by different components of the tumour microenvironment (TME) including cytokines and immune cells. Although angiogenesis has been studied in pituitary adenomas (PAs), the role of individual TME components in PA angiogenesis remains largely unknown. We aimed to characterise the role of the TME components in determining the angiogenesis of PAs, focusing on PA-infiltrating immune cells and the PA-derived cytokine network.<p class="abste...

Non-functioning pituitary adenomas (NFPAs) are the second most common subtype (15-43%) of all clinically presenting pituitary adenomas. Although the primary treatment of symptomatic NFPAs is surgery, gross total resection is achieved only in about 66% of the cases, and 20% of gross total resected tumours recur after 10 years. Despite recent advances in medical management of pituitary tumours, NFPAs remain the only subtype with no widely accepted pharmacological treatment. Expr...

The islet-enriched transcription factor MAFA regulates the expression of genes critical to beta cell function and insulin secretion. We previously described anovel MAFA mutation (c.191C > T, p.S64F) causing familial insulinomatosis and diabetes mellitus, with male carriers more often developing diabetes and females more prone to insulinomatosis. The exact molecular mechanisms underlying these phenotypes are unclear. In this study, we assessed glucose metabolism an...

Introduction: Germline AIP and MEN1 mutations are the main known aetiologies of familial pituitary neuroendocrine tumours (PitNETs), which represent 5% of all PitNETs. We compared the clinical and tumour characteristics of AIP (AIP mut) and MEN1 mutation-positive (MEN1 mut) PitNET patients.Methods: We retrospectively analysed 70 MEN1 mut and 167 AIP mut patients with PitNETs. MEN...