{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:43Z","timestamp":1787027923362,"version":"build-2736575974"},"reference-count":198,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T00:00:00Z","timestamp":1668297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Connshing syndrome (CoSh) (adrenal-related synchronous aldosterone (A) and cortisol (C) excess) represents a distinct entity among PA (primary hyperaldosteronisms) named by W. Arlt et al. in 2017, but the condition has been studied for more than 4 decades. Within the last few years, this is one of the most dynamic topics in hormonally active adrenal lesions due to massive advances in steroids metabolomics, molecular genetics from CYP11B1\/B2 immunostaining to genes constellations, as well as newly designated pathological categories according to the 2022 WHO classification. In gross, PA causes 4\u201310% of all high blood pressure (HBP) cases, and 20% of resistant HBP; subclinical Cushing syndrome (SCS) is identified in one-third of adrenal incidentalomas (AI), while CoSh accounts for 20\u201330% to 77% of PA subjects, depending on the tests used to confirm autonomous C secretion (ACS). The clinical picture overlaps with PA, hypercortisolemia being mild. ACS is suspected in PA if a more severe glucose and cardiovascular profile is identified, or there are larger tumours, ACS being an independent factor risk for kidney damage, and probably also for depression\/anxiety and osteoporotic fractures. It seems that one-third of the PA-ACS group harbours mutations of C-related lines like PRKACA and GNAS. A novel approach means we should perform CYP11B2\/CYP11B1 immunostaining; sometimes negative aldosteronoma for CYP11B1 is surrounded by micronodules or cell clusters with positive CYP11B1 to sustain the C excess. Pitfalls of hormonal assessments in CoSh include the index of suspicion (check for ACS in PA patients) and the interpretation of A\/C ratio during adrenal venous sample. Laparoscopic adrenalectomy is the treatment of choice. Post-operative clinical remission rate is lower in CoSh than PA. The risk of clinically manifested adrenal insufficiency is low, but a synthetic ACTH stimulating testing might help to avoid unnecessary exposure to glucocorticoids therapy. Finally, postponing the choice of surgery may impair the outcome, having noted that long-term therapy with mineralocorticoids receptors antagonists might not act against excessive amounts of C. Awareness of CoSh improves management and overall prognosis.<\/jats:p>","DOI":"10.3390\/diagnostics12112772","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:14:01Z","timestamp":1668399241000},"page":"2772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-3835","authenticated-orcid":false,"given":"Mara","family":"Carsote","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Carol Davila University of Medicine and Pharmacy & C.I. Parhon National Institute of Endocrinology, 011683 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e93136","DOI":"10.1172\/jci.insight.93136","article-title":"Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism","volume":"2","author":"Arlt","year":"2017","journal-title":"JCI Insight"},{"key":"ref_2","unstructured":"(2022, July 08). Available online: https:\/\/www.sciencedaily.com\/releases\/2017\/04\/170421103734.htm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1097\/HJH.0000000000001550","article-title":"The impact of Connshing\u2019s syndrome-mild cortisol excess in primary aldosteronism drives diabetes risk","volume":"35","author":"Beuschlein","year":"2017","journal-title":"J. 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