Endocrine Abstracts

Background: The d3-growth hormone receptor (GHR) polymorphism is a common variant characterized by genomic deletion of exon 3 (d3) of the GHR gene. It could be linked to a better growth response to GH, but the findings are controversial. Due to the lack of IGF-I feedback on the tumoral GH secretion, acromegaly seems to be a good model to study functional characteristics of this polymorphism. Aim of the study was to investigate possible influences of d3-GHR on GH and IGF-I rela...

Celiac disease is a chronic inflammatory autoimmune disorder often associated with other endocrine autoimmune diseases, such as type I diabetes mellitus, Addison’s disease and Hashimoto’s thyroiditis. In these patients, LH, FSH and GH secretion has been poorly investigated. Aim of this study is to evaluate anterior pituitary function, and in particular hypotalamic-pituitary-gonadal (HPG) axis and GH-IGF-I axis, in adult patients with treated celiac disease. For this ...

Introduction: Adrenocortical carcinoma (ACC) is a rare, aggressive tumour with unsatisfactory treatment options in advanced disease. Activation of epithelial to mesenchymal transition (EMT) has been described as causative of metastatic spread in a variety of human cancers. Accordingly, new drugs were developed specifically targeting EMT with a focus on HGF/c-MET and FGF/FGFR signalling. We here asked whether EMT is a relevant mechanism in ACC.Methods: Ex...

Current systemic treatment options for patients with ACCs are far from being satisfactory. DNA damage/repair mechanisms, which involve e.g. ATM/ATR-signalling or RRM1/RRM2 encoded ribonucleotide reductase (RNR) activation commonly contribute to drug resistance. Moreover, also the regulation of RRM2b, the p53-induced alternative to RRM2, is of unclear importance for ACC. Upon extensive drug screening, including a large panel of classical chemotherapies (doxorubicin, etoposide, ...

Background: Adrenal tumours are found in 3-7% of adults. The European guidelines on management of adrenal incidentalomas (first published in 2016 and recently updated) have standardised the management of these patients, but evidence of guideline impact on clinical care is lacking.Methods: Retrospective review of the mode of presentation, radiological characteristics and final diagnosis of a large cohort of patients with ...

Introduction: Up to 3-7% of adults have an adrenal incidentaloma. These are most frequently non-functioning adenomas (NFA) but can be associated with adrenal hormone excess. According to the ESE-ENSAT guidelines on adrenal incidentalomas (2016), an accurate endocrine work-up is recommended.Methods: We provide an extensive retrospective analysis of patients with adrenal tumours referred to a large UK tertiary centre betwe...

Background: Pheochromocytoma is associated with systemic inflammation, but the underlying mechanisms are unclear. Hypothesising a putative effect of catecholamines on immune cells, we investigated the relationship between plasma metanephrine levels and haematological parameters – as surrogates for systemic inflammation – in patients with pheochromocytoma. Moreover, we aimed to assess the influence of preoperative α-blockade treatment on the inflammation-based sc...

Background: Adrenocortical adenomas (ACA) can be associated with different degrees of cortisol excess. Genetic alterations in the cAMP/PKA pathway are observed in up to 60% of cases with overt Cushing syndrome (CS-ACA) and 15% of cases with mild autonomous cortisol secretion (MACS-ACA), while variants in the gene coding for β-catenin (CTNNB1) are more frequent in MACS-ACA and non-functioning adrenal tumours (NFAT). We aimed to test whether somatic variants could ...

Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within the mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating NNT mutations lead to isolated primary adrenal insufficiency, suggesting a selective vulnerability of adrenoc...

Adrenocortical Carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. Here we evaluated a potential new treatment target for ACC, focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within the mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating NNT mutations lead to isolated primary adrenal insufficiency, suggesting a selective vulnerability of adrenoc...