{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:25:44Z","timestamp":1793053544918,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The best approach to patients with adrenal incidentaloma (AI) and possible autonomous cortisol secretion (PACS) is debated. The aim of this study was to assess the metabolic effect of adrenalectomy in AI patients with PACS in relation to cortisol secretion parameters, peripheral activation, and glucocorticoid sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This is a multicenter randomized study (NCT number: NCT04860180).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty-two AI outpatients (40\u201375 years) with AI &amp;gt;1 cm and cortisol after overnight dexamethasone suppression test (F-1mgDST) between 50 and 138 nmol\/L were randomized to adrenalectomy (Arm A) or a conservative approach (Arm B). Fifty-five patients completed the 6-month follow-up, 25 patients in Arm A (17 female patients, aged 62.5 \u00b1 10.4 years) and 30 patients in Arm B (24 female patients, 66.1 \u00b1 9.1 years). Plasma adrenocorticotroph hormone (ACTH), 24-h urinary free cortisol, 24-h urinary free cortisone, F-1mgDST, glucose, lipids, glycated hemoglobin (HbA1c) levels, blood pressure (BP), body weight, and treatment variations were assessed. The 24-h urinary free cortisol\/cortisone ratio (an 11-beta hydroxysteroid dehydrogenase type 2 activity marker), BclI, and the N363S variants of glucocorticoid receptor (GR) polymorphisms were also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BP control improved in 68% and 13% of the subjects in Arm A and Arm B, respectively (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001), and the glycometabolic control improved in 28% and 3.3% of the subjects in Arm A and Arm B patients, respectively (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.02). Arm A subjects more rarely showed the BP and\/or glycometabolic control worsening than Arm B patients (12% and 40%, respectively,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.03). The surgical approach was independently associated with BP amelioration (OR 3.0, 95% CI 3.8\u2013108.3,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) but not with age, F-1mgDST levels, BMI, and hypertension and diabetes mellitus presence at baseline. The 24-h urinary free cortisol\/cortisone ratio and the presence of sensitizing GR polymorphisms were not associated with the surgical outcome. The receiver operating characteristic (ROC) curve analysis showed that the BP control amelioration was associated with F-1mgDST [area under the curve (AUC), 0.82 \u00b1 0.09\n                      <jats:italic>p<\/jats:italic>\n                      = 0.012]. The F-1mgDST cutoff with the best compromise in predicting the BP amelioration was set at 75 nmol\/L (sensitivity 77%, specificity 75%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AI patients with PACS benefit from surgery in terms of BP and glycometabolic control.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2022.898084","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:16:59Z","timestamp":1654168619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":58,"title":["Adrenalectomy Improves Blood Pressure and Metabolic Control in Patients With Possible Autonomous Cortisol Secretion: Results of a RCT"],"prefix":"10.3389","volume":"13","author":[{"given":"Valentina","family":"Morelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Frigerio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Aresta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Passeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Pugliese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimilano","family":"Copetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Fustinoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Polledri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Corbetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Arosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Scillitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Chiodini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1530\/EJE-16-0467","article-title":"Management of Adrenal Incidentalomas: European Society of Endocrinology Clinical Practice Guideline in Collaboration With the European Network for the Study of Adrenal Tumors","volume":"175","author":"Fassnacht","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1530\/EJE-17-0047","article-title":"Cardiovascular Events in Patients With Mild Autonomous Cortisol Secretion: Analysis With Artificial Neural Networks","volume":"177","author":"Morelli","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/S2213-8587(13)70211-0","article-title":"Cardiovascular Events and Mortality in Patients With Adrenal Incidentalomas That are Either non\u2013Secreting or Associated With Intermediate Phenotype or Subclinical Cushing\u2019s Syndrome: A 15\u2013Year Retrospective Study","volume":"2","author":"Di Dalmazi","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3007","article-title":"Cortisol as a Marker for Increased Mortality in Patients With Incidental Adrenocortical Adenomas","volume":"99","author":"Debono","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2018.01.003","article-title":"Recent Advances on Subclinical Hypercortisolism","volume":"47","author":"Zavatta","year":"2018","journal-title":"Endocrinol Metab Clinics North America"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3527","article-title":"Long\u2013term Follow\u2013Up in Adrenal Incidentalomas: An Italian Multicenter Study","volume":"99","author":"Morelli","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-017-1400-8","article-title":"Increased Mortality in Patients With Adrenal Incidentalomas and Autonomous Cortisol Secretion: A 13\u2013Year Retrospective Study From One Center","volume":"58","author":"Patrova","year":"2017","journal-title":"Endocrine"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00382","article-title":"Adrenal Hypercortisolism: A Closer Look at Screening, Diagnosis, and Important Considerations of Different Testing Modalities","volume":"3","author":"Chiodini","year":"2019","journal-title":"J Endocr Soc"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/jendso\/bvaa079","article-title":"Defining Nonfunctioning Adrenal Adenomas on the Basis of the Occurrence of Hypocortisolism After Adrenalectomy","volume":"4","author":"Eller\u2013Vainicher","year":"2020","journal-title":"J Endocr Soc"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2018.03.013","article-title":"Do the Diagnostic Criteria for Subclinical Hypercortisolism Exist","volume":"79","author":"Tabarin","year":"2018","journal-title":"Ann Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1210\/JC.2018-01029","article-title":"Suppressed ACTH Is Frequently Unrelated to Autonomous Cortisol Secretion in Patients With Adrenal Incidentalomas","volume":"104","author":"Olsen","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2010.03794.x","article-title":"Subclinical Hypercortisolism: Correlation Between Biochemical Diagnostic Criteria and Clinical Aspects","volume":"73","author":"Morelli","year":"2010","journal-title":"Clin Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-1039","article-title":"Progressively Increased Patterns of Subclinical Cortisol Hypersecretion in Adrenal Incidentalomas Differently Predict Major Metabolic and Cardiovascular Outcomes: A Large Cross\u2013Sectional Study","volume":"166","author":"Di Dalmazi","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0803","article-title":"The Role of Salivary Cortisol Measured by Liquid Chromatographytandem Mass Spectrometry in the Diagnosis of Subclinical Hypercortisolism","volume":"168","author":"Palmieri","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-020-01484-2","article-title":"Hidden Hypercortisolism: A Too Frequently Neglected Clinical Condition","volume":"44","author":"Giovanelli","year":"2021","journal-title":"J Endocrinol Invest"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-020-02212-9","article-title":"Prediction of Hypertension, Diabetes and Fractures in Eucortisolemic Women by Measuring Parameters of Cortisol Milieu","volume":"68","author":"Morelli","year":"2020","journal-title":"Endocrine"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0465","article-title":"Improvement of Cardiovascular Risk Factors After Adrenalectomy in Patients With Adrenal Tumors and Subclinical Cushing\u2019s Syndrome: A Systematic Review and Meta\u2013Analysis","volume":"175","author":"Bancos","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31819a47d2","article-title":"Surgical Versus Conservative Management for Subclinical Cushing Syndrome in Adrenal Incidentalomas: A Prospective Randomized Study","volume":"249","author":"Toniato","year":"2009","journal-title":"Ann Surg"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0125","article-title":"The Diagnosis of Cushing\u2019s Syndrome: An Endocrine Society Clinical Practice Guideline","volume":"93","author":"Nieman","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.6601","article-title":"High\u2013throughput Determination of Cortisol, Cortisone, and Melatonin in Oral Fluid by on\u2013Line Turbulent Flow Liquid Chromatography Interfaced With Liquid Chromatography\/Tandem Mass Spectrometry","volume":"27","author":"Fustinoni","year":"2013","journal-title":"Rapid Commun Mass Spectrom"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3109\/08037051.2014.868629","article-title":"2013 ESH\/ESC Practice Guidelines for the Management of Arterial Hypertension","volume":"23","author":"Mancia","year":"2014","journal-title":"Blood Pressure"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-S002","article-title":"2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetesd2019","volume":"42","author":"Care","year":"2019","journal-title":"Diabetes Care"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/circ.106.25.3143","article-title":"Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report","volume":"106","year":"2002","journal-title":"Circulation"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802215","article-title":"Updated Review on the Benefits of Weight Loss","volume":"26","author":"Vidal","year":"2002","journal-title":"Int J Obes"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2010.02330.x","article-title":"Role of Glucocorticoid Receptor Polymorphism in Adrenal Incidentalomas","volume":"40","author":"Morelli","year":"2010","journal-title":"Eur J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0602","article-title":"Accuracy of Several Parameters of Hypothalamic\u2013Pituitary\u2013Adrenal Axis Activity in Predicting Before Surgery the Metabolic Effects of the Removal of an Adrenal Incidentaloma","volume":"163","author":"Eller\u2013Vainicher","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1530\/EJE-18-0608","article-title":"European Society of Endocrinology Clinical Practice Guidelines on the Management of Adrenocortical Carcinoma in Adults, in Collaboration With the European Network for the Study of Adrenal Tumors","volume":"179","author":"Fassnacht","year":"2018","journal-title":"Eur J Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-1017-3","article-title":"Six Controversial Issues on Subclinical Cushing\u2019s Syndrome","volume":"56","author":"Chiodini","year":"2017","journal-title":"Endocrine"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0602","article-title":"Accuracy of Several Parameters of Hypothalamic\u2013Pituitary\u2013Adrenal Axis Activity in Predicting Before Surgery the Metabolic Effects of the Removal of an Adrenal Incidentaloma","volume":"163","author":"Eller\u2013Vainicher","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.794197","article-title":"Attenuation Value in Adrenal Incidentalomas: A Longitudinal Study","volume":"12","author":"Ceccato","year":"2021","journal-title":"Front Endocrinol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00382","article-title":"Adrenal Hypercortisolism: A Closer Look at Screening, Diagnosis, and Important Considerations of Different Testing Modalities","volume":"3","author":"Chiodini","year":"2019","journal-title":"J Endocr Soc"},{"key":"B32","doi-asserted-by":"publisher","first-page":"11521","DOI":"10.3390\/ijms222111521","article-title":"Management and Medical Therapy of Mild Hypercortisolism","volume":"22","author":"Favero","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200018030-00001","article-title":"The Role of the 11\u03b2\u2013Hydroxysteroid Dehydrogenase Type 2 in Human Hypertension","volume":"18","author":"Ferrari","year":"2000","journal-title":"J Hypertens"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-015-0763-y","article-title":"The Activity of 11\u03b2\u2013Hydroxysteroid Dehydrogenase Type 2 Enzyme and Cortisol Secretion in Patients With Adrenal Incidentalomas","volume":"53","author":"Morelli","year":"2016","journal-title":"Endocrine"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-020-01197-6","article-title":"Dexamethasone Measurement During Low\u2013Dose Suppression Test for Suspected Hypercortisolism: Threshold Development With and Validation","volume":"43","author":"Ceccato","year":"2020","journal-title":"J Endocrinol Invest"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2016.05.002","article-title":"Establishment of Revised Diagnostic Cut\u2013Offs for Adrenal Laboratory Investigation Using the New Roche Diagnostics Elecsys\u00ae Cortisol II Assay","volume":"77","author":"Raverot","year":"2016","journal-title":"Ann Endocrinol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.898084\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:17:02Z","timestamp":1654168622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.898084\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,2]]},"references-count":36,"alternative-id":["10.3389\/fendo.2022.898084"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.898084","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,2]]},"article-number":"898084"}}