{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:13:11Z","timestamp":1780409591032,"version":"3.54.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"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>Introduction<\/jats:title>\n                    <jats:p>In the last few years, the use of medical treatment in Cushing\u2019s disease (CD) has increased thanks to the availability of new molecules. Nevertheless, real-life data on combination treatments are still lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a retrospective monocentric study evaluating the real-life efficacy and safety of pasireotide alone or when combined with cabergoline or metyrapone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 18 patients (94% women; median age, 45 years) with active CD received pasireotide (median, 8 months), followed by a combination treatment (median, 22 months) with either cabergoline (2\/9) or metyrapone (7\/9) for half of the patients. Pasireotide alone significantly reduced urinary free cortisol (UFC) and late-night salivary cortisol (LNSC) (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01), achieving normal values in 59% and 38% of cases, respectively. The second cortisol-lowering agent tended to further reduce UFC (overall normalization, 67%) but had little effect on LNSC. Pasireotide led to significant hyperglycemia in 61% of cases, while the add-on drug was well-tolerated. Comorbidities were analyzed accounting for the individual cardiovascular risk and for changes in concomitant treatments. Half of the patients showed improved pressure profile. Cholesterol levels tended to decrease, and a significant weight loss was observed (&amp;gt;5% in 47% of cases). Add-on treatment with dose reduction of pasireotide allowed better glycemic control in one of two cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our experience confirms the efficacy of pasireotide on the UFC, especially in combined regimens, but also the difficulty of restoring circadian rhythm in CD. This is the first study to report metyrapone add-on to pasireotide, but larger studies are needed to further investigate this association. Pasireotide surely worsens glucose homeostasis, but its positive effects, alone or combined, on blood pressure, lipid profile, and body weight justify its use under careful hyperglycemia management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1695342","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T05:16:20Z","timestamp":1763010980000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Real-life data on pasireotide in monotherapy or combined in active Cushing\u2019s disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Alessandro","family":"Mondin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Ceccato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Scaroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Denaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Manara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto Maria","family":"Robertazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Barbot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00235-7","article-title":"Consensus on diagnosis and management of Cushing\u2019s disease: a guideline update","volume":"9","author":"Fleseriu","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S2213-8587(17)30326-1","article-title":"Efficacy and safety of once-monthly pasireotide in Cushing\u2019s disease: a 12 month clinical trial","volume":"6","author":"Lacroix","year":"2018","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac178","article-title":"Randomized trial of osilodrostat for the treatment of cushing disease","volume":"107","author":"Gadelha","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.662865","article-title":"Relacorilant, a selective glucocorticoid receptor modulator, induces clinical improvements in patients with cushing syndrome: results from A prospective, open-label phase 2 study","volume":"12","author":"Pivonello","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-0978-6","article-title":"Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing\u2019s disease: 12-month, Phase III pasireotide study","volume":"54","author":"Findling","year":"2016","journal-title":"Endocrine"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvae201","article-title":"Improved clinical outcomes during long-term osilodrostat treatment of cushing disease with normalization of late-night salivary cortisol and urinary free cortisol","volume":"9","author":"Newell-Price","year":"2024","journal-title":"J Endocr Soc"},{"key":"B7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1677\/JME-08-0110","article-title":"Differential regulation of human dopamine D2 and somatostatin receptor subtype expression by glucocorticoids in vitro","volume":"42","author":"de Bruin","year":"2009","journal-title":"J Mol Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-017-1316-3","article-title":"Long-term treatment of Cushing\u2019s disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial","volume":"57","author":"Petersenn","year":"2017","journal-title":"Endocrine"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.935759","article-title":"Pasireotide-induced shrinkage in GH and ACTH secreting pituitary adenoma: A systematic review and meta-analysis","volume":"13","author":"Mondin","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1000094","article-title":"Pasireotide alone or with cabergoline and ketoconazole in cushing\u2019s disease","volume":"362","author":"Feelders","year":"2010","journal-title":"New Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1165681","article-title":"Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing\u2019s disease","volume":"14","author":"Feelders","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1669-2","article-title":"Effects of pasireotide treatment on coagulative profile: a prospective study in patients with Cushing\u2019s disease","volume":"62","author":"Barbot","year":"2018","journal-title":"Endocrine"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-020-01055-x","article-title":"Is pasireotide-induced diabetes mellitus predictable? A pilot study on the effect of a single dose of pasireotide on glucose homeostasis","volume":"23","author":"Barbot","year":"2020","journal-title":"Pituitary"},{"key":"B14","doi-asserted-by":"publisher","first-page":"5217","DOI":"10.3390\/ijms23095217","article-title":"Incretin response to mixed meal challenge in active cushing\u2019s disease and after pasireotide therapy","volume":"23","author":"Barbot","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac686","article-title":"Dynamic testing for differential diagnosis of ACTH-dependent cushing syndrome: A systematic review and meta-analysis","volume":"108","author":"Ceccato","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12259","article-title":"High variability in baseline urinary free cortisol values in patients with Cushing\u2019s disease","volume":"80","author":"Petersenn","year":"2014","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02020","article-title":"Variability of late-night salivary cortisol in cushing disease: A prospective study","volume":"103","author":"Sandouk","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","article-title":"2024 ESC Guidelines for the management of elevated blood pressure and hypertension","volume":"45","author":"McEvoy","year":"2024","journal-title":"Eur Heart J"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S002","article-title":"Classification and diagnosis of diabetes: standards of medical care in diabetes-2022","volume":"45","year":"2022","journal-title":"Diabetes Care"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk","volume":"41","author":"Mach","year":"2020","journal-title":"Eur Heart J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1159\/000442721","article-title":"European guidelines for obesity management in adults","volume":"8","author":"Yumuk","year":"2015","journal-title":"Obes Facts"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1524-5","article-title":"Pasireotide treatment reduces cardiometabolic risk in Cushing\u2019s disease patients: an Italian, multicenter study","volume":"61","author":"Albani","year":"2018","journal-title":"Endocrine"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-009-0209-8","article-title":"Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing\u2019s disease","volume":"13","author":"Vilar","year":"2010","journal-title":"Pituitary"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0536","article-title":"Mitotane, metyrapone, and ketoconazole combination therapy as an alternative to rescue adrenalectomy for severe ACTH-dependent cushing\u2019s syndrome","volume":"96","author":"Kamenick\u00fd","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2012.04424.x","article-title":"A reappraisal of the medical therapy with steroidogenesis inhibitors in C ushing\u2019s syndrome","volume":"77","author":"Valassi","year":"2012","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-013-0475-3","article-title":"Combination therapy for Cushing\u2019s disease: effectiveness of two schedules of treatment. Should we start with cabergoline or ketoconazole","volume":"17","author":"Barbot","year":"2014","journal-title":"Pituitary"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-14-0913","article-title":"Rapid control of severe neoplastic hypercortisolism with metyrapone and ketoconazole","volume":"172","author":"Corcuff","year":"2015","journal-title":"Eur J Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac691","article-title":"Efficacy and safety of osilodrostat in paraneoplastic cushing syndrome: A real-world multicenter study in France","volume":"108","author":"Dormoy","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvaf089","article-title":"A prospective trial with ketoconazole induction therapy and octreotide maintenance treatment for cushing\u2019s disease","volume":"9","author":"Paes","year":"2025","journal-title":"J Endocr Soc"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-015-0641-x","article-title":"Medical combination therapies in Cushing\u2019s disease","volume":"18","author":"Vilar","year":"2015","journal-title":"Pituitary"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1060884","article-title":"Individualized medical treatment options in Cushing disease","volume":"13","author":"Gilis-Januszewska","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"6469","DOI":"10.3390\/ijms23126469","article-title":"The role of glucocorticoid receptor in the pathophysiology of pituitary corticotroph adenomas","volume":"23","author":"Regazzo","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B33","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":"B34","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0695","article-title":"Use of late-night salivary cortisol to monitor response to medical treatment in Cushing\u2019s disease","volume":"182","author":"Newell-Price","year":"2020","journal-title":"Eur J Endocrinol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-20-0066","article-title":"Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy","volume":"246","author":"Minnetti","year":"2020","journal-title":"J Endocrinol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.42.413","article-title":"Effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors: in vitro culture studies","volume":"42","author":"Eguchi","year":"1995","journal-title":"Endocr J"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.42.153","article-title":"In vivo effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors","volume":"42","author":"Eguchi","year":"1995","journal-title":"Endocr J"},{"key":"B38","doi-asserted-by":"crossref","DOI":"10.18632\/oncotarget.5744","article-title":"Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline","volume":"6","author":"Lin","year":"2015","journal-title":"Oncotarget"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1245","article-title":"The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas","volume":"91","author":"Batista","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.mce.2014.07.001","article-title":"Inhibitory effects of SOM230 on adrenocorticotropic hormone production and corticotroph tumor cell proliferation in vitro and in vivo","volume":"394","author":"Murasawa","year":"2014","journal-title":"Mol Cell Endocrinol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1677\/ERC-06-0026","article-title":"Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion","volume":"14","author":"Zatelli","year":"2007","journal-title":"Endocr Relat Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1007\/s11102-021-01161-4","article-title":"Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study","volume":"24","author":"Samson","year":"2021","journal-title":"Pituitary"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1771","article-title":"Hyperglycemia associated with pasireotide: results from a mechanistic study in healthy volunteers","volume":"98","author":"Henry","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14081","article-title":"Long-term efficacy and safety of once-monthly pasireotide in Cushing\u2019s disease: A Phase III extension study","volume":"91","author":"Fleseriu","year":"2019","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.17925\/EE.2024.20.1.8","article-title":"Osilodrostat: A novel potent inhibitor of 11-beta-hydroxylase for the treatment of cushing\u2019s syndrome","volume":"20","author":"Pivonello","year":"2024","journal-title":"touchREVIEWS. Endocrinology"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-025-02572-x","article-title":"Cardiometabolic complications after Cushing\u2019s disease remission","volume":"48","author":"Tizianel","year":"2025","journal-title":"J Endocrinol Invest"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12431","article-title":"Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing\u2019s disease: results from a Phase III study","volume":"81","author":"Pivonello","year":"2014","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000003252","article-title":"Diagnosis and management of hypertension in patients with Cushing\u2019s syndrome: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension","volume":"40","author":"Fallo","year":"2022","journal-title":"J Hypertens"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1695342\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T05:16:21Z","timestamp":1763010981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1695342\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":48,"alternative-id":["10.3389\/fendo.2025.1695342"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1695342","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,13]]},"article-number":"1695342"}}