Endocrine Abstracts

Background: Primary Aldosteronism (PA) is the commonest curable cause of hypertension. Whole exome sequencing (WES) of an aldosterone producing adenoma from a 46-year-old man with resistant hypertension revealed a novel somatic mutation (Val380Asp) of the single transmembrane domain of Cell Adhesion Molecule-1 (CADM1). A Gly379Asp mutation was identified by WES of a PA patient in Munich. Both patients were cured of hypertension by adrenalectomy.Method: A...

Background: PA is the commonest curable cause of hypertension. Whole exome sequencing (WES) in 2011 and 2013 identified common somatic mutations in genes regulating membrane polarisation in 60-80% of aldosterone-producing adenomas (APA). In search of the missing variants, we undertook further WES. One APA from a 46-year-old gentleman revealed a novel somatic mutation (Val380Asp); which introduced a charged amino-acid into the single transmembrane domain of Cell Adhesion Molecu...

Background: Sporadic aldosterone-producing adenomas (APA) are relevant cause of endocrine related hypertension in Primary Aldosteronism (PA). Next generation sequencing techniques have identified somatic mutations in APA harbored in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CTNNB1 and PRKACA genes. Yet, a number of APA harbor no mutations in candidate genes (designated as wild type, WT) and little is known about genotype/phenotype correlation.Objectives: We invest...

Introduction: Primary aldosteronism (PA) is mainly caused by unilateral aldosterone-producing adenomas (APA) or bilateral adrenal hyperplasia (BAH). Subtype differentiation relies on the invasive and technically challenging adrenal venous sampling (AVS). We recently demonstrated the potential utility of peripheral plasma steroid profiling by LC-MS/MS to distinguish APA and BAH. We tested the following hypotheses: first, if steroid profiling in combination with AVS, effectively...

Aldosterone-producing adenomas (APAs) are the most frequent cause of primary aldosteronism (PA). Somatic mutations of KCNJ5, ATP1A1, CACNA1D and ATP2B3 are involved in APAs formation while CTNNB1 and GNAS somatic mutations have been described in both APAs and in cortisol-producing adenomas (CPAs). In contrast, mutations of PRKACA coding for the catalytic subunit of protein kinase A have been yet only identified in ...

Introduction: The regular diagnostic workup for primary aldosteronism (PA) can be very demanding and involves multiple invasive as well as time and cost intensive diagnostic tests. Here we have explored the value of urinary steroid metabolome analysis in the diagnosis and differential diagnosis of PA. Previously, urinary 3α,5β-tetrahydroaldosterone (THAldo) has been suggested as a reliable screening test for PA and serum 18-oxocortisol and 18-hydroxycortisol have bee...

Objective: Adrenal vein sampling (AVS) is recognised by Endocrine Society guidelines as the only reliable mean to distinguish between aldosterone producing adenomas and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). However, AVS protocols are not standardised and vary between centres. The objective of the present study was to assess whether the presence or absence of contralateral adrenal (CL) suppression has an impact on the postope...

Objective: Bilateral adrenalectomy (BADX) is an important treatment option for patients with Cushing’s syndrome (CS). The outcome of this procedure has not been studied well.The aim was to analyze long-term outcome of CS patients treated with BADX.Design: Fifty patients with BADX treated since 1990 in two German centers were identified. 34 patients had Cushing’s disease (CD), nine ectopic Cushing-syndrome (ECS), and seven...

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...