Endocrine Abstracts

Background: Genetic alterations underlying the pathogenesis of autonomous cortisol secretion and early adrenocortical tumorigenesis have been identified in 40% of adrenocortical tumors (ACT). Nonetheless, the molecular events leading to development of ACT and steroid secretion remain obscure for a large proportion of patients.Aim: Aims of our study were to investigate the relationship between transcriptome profile and genetic background in a large series...

The effective treatment and optimal prognosis of hypercortisolism (Cushing’s syndrome – CS) depend on accurate and early diagnosis. However, hormonal assays can be complex, requiring multiple tests, and not predictive for any related complications, neither for their duration and severity. Identifying novel, specific and easily measurable biomarkers may improve CS diagnosis as well as the evaluation of complications. Since stress-associated epigenetic markers can be...

Rationale: Endothelial dysfunction (ED) is a hallmark of primary aldosteronism and paves the way for subsequent atherosclerotic disease. Past research has confirmed that one factor involved in ED is disturbed nitric oxide (NO) signalling. Since defects in NO release alone cannot explain the whole effect, we set out to address the role of endothelial CYP-expoygenase products (epoxyeicosatrienoic acids, EETs) in aldosterone-mediated endothelial dysfunction.<p class="abstext"...

IntroductionSomatic USP8 mutations are found in around 50% of Cushing’s disease tumours and are located in a single mutational hotspot that contains the recognition site for 14–3-3. These proteins bind to phosphoserine recognition motifs to alter the function and location of their target proteins, and are deregulated in several cancers. AimTo explore the expression and function of 14–3-3 prot...

IntroductionTP53 mutations have been rarely reported in pituitary tumours. Recently two exploratory exome sequencing studies have identified somatic TP53 mutations in a small number of functional corticotroph tumours (6/18 and 4/10) with USP8 wild type (wt) status, suggesting that they may be more frequent than previously thought. Nevertheless, the clinical impact of those mutations is still unknown.AimTo det...

Background: Confirmation of primary aldosteronism (PA) with the saline infusion test (SIT) requires accurate measurements of plasma aldosterone, best achieved by mass spectrometry. Performance of the test and appropriate cut-offs remain inadequately defined.Design and methods: This prospective multicenter cohort study involved 451 patients with suspected PA who underwent a seated SIT. Among these, there were 90 and 76 in whom PA was respectively confirmed and excluded based on...

Background: Diagnostic stratification of patients with suspected primary aldosteronism (PA) is a multistep process reliant on tests that are not infallible. Only through prospective studies can diagnostic accuracy be appropriately assessed.Methods: The PROSALDO trial enrolled 819 patients between 2019 and 2023 to assess steroid profiles against routine tests for diagnostic stratification. A combination of these tests and outcome assessments, including me...

Background: Treatment of adrenocortical carcinoma (ACC) is unsatisfactory in advanced stages. Oral mitotane remains a mainstay of treatment. Response rates of ACC to immune checkpoint inhibition (ICI) are disappointing and markers of response have not been identified. Tumoural infiltration with cells of the adaptive immune system is sparse in ACC tissue. Growth/differentiation factor 15 (GDF-15) is a cytokine that has been described to impair tumoral immune infiltration and is...

Introduction: Bilateral Macronodular Adrenocortical Disease (BMAD) is a rare cause of Cushing syndrome due to bilateral adrenocortical macronodules. Germline inactivating variants of the tumor suppressor gene ARMC5 have been described by our group 10 years ago and are responsible for 20-25% of apparently sporadic BMAD cases and 80% of familial presentations. ARMC5 patients present with a more pronounced phenotype than wild-type patients, in terms of cortisol ...

Background: Steroid synthesis inhibitors, like metyrapone, osilodrostat, and ketoconazole are used as second-line treatment in all types of endogenous Cushing’s syndrome (CS). However, a direct comparison of these three drugs is missing. This study aimed to compare these drugs in the short-term therapy of CS.Design: Retrospective multicenter study involving 15 European centers.Methods: Patients with CS treated with metyrapone,...