Endocrine Abstracts

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,...

Introduction and rationale: Cushing’s syndrome (CS) is a rare disease with hypercortisolism caused either by ACTH excess from a pituitary or non-pituitary tumor or by an ACTH-independent primary adrenal overproduction of cortisol. It is associated with significant comorbidities potentially lethal: hypertension, diabetes, coagulopathy, cardiovascular disease, infections, and osteoporotic fractures. It is usually managed by surgery and/or medical treatment with steroidogene...

Recent studies have reported a high prevalence of USP8 mutations in corticotroph adenomas causing Cushing’s disease. Nelson’s syndrome is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory Cushing’s disease that is caused by the development of an ACTH-secreting tumor in the pituitary gland. Whether USP8 alterations are also present in Nelson’s tumors has not been studied in detail so far....

Genetic alterations affecting the PKA/cAMP pathway are commonly found in cortisol-producing adrenocortical adenomas (ACAs), while activating mutations in the gene coding for β-catenin (CTNNB1) have been reported in both adenomas and carcinomas. However, the molecular pathogenesis of most ACAs is still unclear. Aim of the study was a comprehensive genetic characterization of sporadic ACAs and the identification of novel molecular markers involved in adrenal tumori...

Background and Methods: Corticotropin-independent Cushing’s syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis of cortisol producing adrenal adenomas is not well understood. Therefore, exome sequencing was performed in 10 cortisol-producing adenomas and recurrent mutations in candidate genes were evaluated in additional 171 patients with adrenocortical tumors. In addition, genome-wide copy number analysis was performed in 35 pati...

Metyrapone treatment in endogenous Cushing’s syndrome. Results from a prospective multicenter, open-label, phase III/IV study: PROMPTBackground: Metyrapone is a steroidogenesis inhibitor approved in Europe for the treatment of endogenous Cushing’s syndrome (CS) based on observational retrospective studies published over more than 50 years. We present data from the first prospective study designed to confirm metyrapone efficacy and good tolera...