Endocrine Abstracts

Background: Adrenocortical cancer (ACC) is an aggressive tumour with heterogeneous prognosis. Recently integrated genomics reported distinct genomic alterations: transcriptome “C1A” (high expression of proliferation/cell cycle-related genes) vs “C1B”, “CIMP” (CpG islands hypermethylation) vs “non-CIMP”, chromosome alterations “Noisy” (numerous and anarchic alterations) vs “Chromosomal” (extended patterns of loss of he...

Androgen receptor (AR) signaling is the main driver for prostate cancer progression and androgen ablation is the treatment of choice for tumors that spread beyond the prostate. Efficient at first, androgen ablation fails due in part to altered cell signaling and expression of AR spice variants. Cell signaling in prostate cancer is regulated by dual specificity phosphatases and tumor suppressors INPP4B and PTEN that are lost with prostate cancer progression. Loss of PTEN destab...

Primary Aldosteronism (PA), due to a unilateral aldosterone-producing adenoma of the adrenal (APA), is the commonest curable cause of Hypertension, but the prospects for cure fall with age. APAs rarely increase in size, suggesting an origin much earlier than the development of resistant hypertension. Most APAs have gain-of-function somatic mutations which result in increased Ca2+ entry, and constitutive activation of aldosterone production. Women with larger APAs, a...

A 33 year-old male bus driver with long standing pemphigus requiring high dose prednisolone, presented with acromegaly in 2001. MRI pituitary revealed a 2×2×0.5 cm pituitary adenoma and his GH levels of 14.8–16.4 nmo/L throughout and were not suppressible with glucose. His IGF1 was 191 nmol/l (normal range: 13–64 nmol/L), Prolactin 6,557 milliunit/L, testosterone 2 nmol/L and cortisol uninterpretable as he was on prednisolone. Trans-sphenoidal hypophysectom...

Differentiated thyroid cancer (DTC) of papillary (PTC) and follicular (FTC) types with invasive loco-regional or metastatic disease, poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), as well as the C-cell derived medullary thyroid cancers (MTC), represent the major cause of mortality amongst thyroid cancer patients. Because such patients are resistant to standard therapy, they may be excellent candidates for innovative adjuvant approaches such as molecular tar...

Background: Adrenocortical carcinoma (ACC) has a heterogeneous prognosis and current medical therapies have limited efficacy in its advanced stages. Genome-wide multi-omics-studies identified molecular patterns associated with clinical outcome. Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine.Methods: 117 tumor samples from 107 AC...

Primary Aldosteronism (PA), due to a unilateral aldosterone-producing adenoma of the adrenal (APA), is the commonest curable cause of Hypertension, but the prospects for cure fall with age. APAs rarely increase in size, suggesting an origin much earlier than the development of resistant hypertension. Most APAs have gain-of-function somatic mutations which result in increased Ca2+ entry, and constitutive activation of aldosterone production. Women with larger APAs, a...

Background: Vascular adhesion protein-1 (VAP-1) is a novel driver of tissue inflammation and fibrosis and may contribute to fibrotic complications of neuroendocrine tumours (NETs). We studied the VAP-1 expression in midgut NETs, which are associated with desmoplasia, and carcinoid heart disease (CHD), a significant complication of metastatic midgut NETs.Methods: Immunohistochemical analysis of paraffin-embedded midgut NETs and CHD valves were stained for...

Background: Our Diabetes Team look after approximately 220 T1DM patients aged 0–17 years. In 2014/15 NPDA we ranked amongst the top 5 paediatric units with mean HBA1c <65 mmol/mol. Susequently our ranking slipped, with increased mean HBA1c and fewer patients achieving HBA1c <58 mmol/mol.Objectives: We recognised a particular problem with poor control in the first year after diagnosis and identified the need to drive change to be able to achi...

Recently, we provided the first integrated genomic classification of pituitary neuroendocrine tumors (PitNETs), on a series of 134 tumors. This series covered all histological, secretion, invasion and growth speed types. This molecular classification supports the importance of pituitary lineage as proposed by the World Health Organization 2017 classification, but also individualizes new entities. Indeed, corticotroph tumors are split into three distinct molecular groups. In ad...