Endocrine Abstracts

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...

Protein Kinase A (PKA) consists of two catalytic and two regulatory subunits with several isoforms (Cα,β,γ, RIα,IIα,Iβ,IIβ). In 30–40% of cortisol-producing adrenocortical adenomas (CPA) heterozygous activating somatic mutations in the catalytic subunit α (Cα) of PKA have been found. Previous reports found strikingly reduced levels of RIIβ in CPA compared to other adrenocortical tumors. Here, we investigated the correlatio...

Background: Adjuvant mitotane therapy is frequently used in Europe following surgery for adrenocortical carcinoma (ACC). Management of adjuvant mitotane is mainly empirical and a major open question is the optimal duration of therapy, because no study has ever addressed this issue.Objective: We aimed to assess the outcome of ACC patients who were treated with adjuvant mitotane for at least one year following surgery and then discontinued therapy for othe...

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...

Introduction: Adrenocortical carcinoma (ACC) is an aggressive malignancy with a high rate of recurrence. Regular post-operative follow-up imaging is necessary, but associated with high radiation exposure and frequent diagnostic ambiguity. Urine steroid metabolomics has recently been introduced as a novel diagnostic tool for the detection of adrenocortical malignancy in patients with adrenal incidentalomas. Here we present the first clinical study assessing the performance of t...

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...