{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:20Z","timestamp":1783574120118,"version":"3.55.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"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:p>Evidence on cyclic Cushing\u2019s syndrome (cCS) is limited. Due to its rarity and diagnostic challenges, some patients remain undiagnosed and experience life-threatening episodes of hyper- and hypocortisolemia. We present a case of a 68-year-old male with a 5-year history of recurrent hospitalizations due to infections, sepsis, and episodes of blood pressure and glycemic instabilities, who was admitted to the Endocrinology Department for evaluation of bilateral adrenal incidentalomas. Physical examination revealed cushingoid features, and biochemical tests confirmed ACTH-dependent CS, with dynamic tests suggesting ectopic origin. Retrospective review showed several peaks of hypercortisolemia separated by spontaneous remissions. These fluctuations correlated with severe infections, hypertension, and hyperglycemia, followed by hypotension and improved metabolic control. Medical therapy with steroidogenesis inhibitors in a block-and-replace regimen resulted in sustained biochemical and clinical stabilization. Imaging failed to identify the ACTH source; therefore inferior petrosal sinus sampling is planned to definitively establish the etiology of CS. This case illustrates the unpredictable nature of cCS and the considerable challenges it poses for both diagnosis and management, emphasizing the need for individualized therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fendo.2026.1788064","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:35Z","timestamp":1783571015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Continuous block-and-replace strategy with osilodrostat in a patient with cyclic Cushing\u2019s syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Wiktoria","family":"Suchy","sequence":"first","affiliation":[{"name":"Chair and Department of Endocrinology, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Minasyan","sequence":"additional","affiliation":[{"name":"Chair and Department of Endocrinology, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Gamrat-\u017bmuda","sequence":"additional","affiliation":[{"name":"Chair and Department of Endocrinology, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Hubalewska-Dydejczyk","sequence":"additional","affiliation":[{"name":"Chair and Department of Endocrinology, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Gilis-Januszewska","sequence":"additional","affiliation":[{"name":"Chair and Department of Endocrinology, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S2213-8587(23)00150-X","article-title":"Diagnostic challenges in cyclic Cushing's syndrome: a systematic review","volume":"11","author":"Nowak","year":"2023","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(25)00249-9","article-title":"Cycle characterisation and clinical complications in patients with cyclic Cushing's syndrome: insights from an international retrospective cohort study","volume":"13","author":"Nowak","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2023.102908","article-title":"Pharmacological treatment of Cushing's syndrome","volume":"54","author":"Castinetti","year":"2023","journal-title":"Arch Med Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00235-7","article-title":"Consensus on diagnosis and management of Cushing's disease: a guideline update","volume":"9","author":"Fleseriu","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-026-10020-1","article-title":"Use of osilodrostat in a block-and-replace and titration strategy for Cushing's syndrome: a position paper by French experts","volume":"27","author":"Castinetti","year":"2026","journal-title":"Rev Endocr Metab Disord"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae864","article-title":"Approach to the patient with cyclical Cushing syndrome","volume":"110","author":"Ferriere","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000346","article-title":"Cyclic ACTH-secreting thymic carcinoid: a case report and review of the literature","volume":"65","author":"Lamback","year":"2021","journal-title":"Arch Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/pcn.12363","article-title":"Cyclic Cushing's syndrome mimicking bipolar disorder","volume":"70","author":"Tsai","year":"2016","journal-title":"Psychiatry Clin Neurosci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-55-3-531","article-title":"Dynamics of adrenocorticotropin (ACTH) secretion in cyclic Cushing's syndrome: evidence for more than one abnormal ACTH biorhythm","volume":"55","author":"Jordan","year":"1982","journal-title":"J Clin Endocrinol Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/BF03349657","article-title":"Cyclical Cushing's disease and its successful control under sodium valproate","volume":"13","author":"Beckers","year":"1990","journal-title":"J Endocrinol Invest"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.35.207","article-title":"Cyclic Cushing's disease in long-term remission with a daily low dose of bromocriptine","volume":"35","author":"Adachi","year":"1996","journal-title":"Intern Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.63.744.887","article-title":"Ectopic Cushing's syndrome with periodic hormonogenesis--a case suggesting a pathogenetic mechanism","volume":"63","author":"Estopi\u00f1\u00e1n","year":"1987","journal-title":"Postgrad Med J"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-2855","article-title":"Cushing syndrome due to ACTH-secreting pheochromocytoma, aggravated by glucocorticoid-driven positive-feedback loop","volume":"101","author":"Sakuma","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02268","article-title":"ACTH-dependent cyclic Cushing syndrome triggered by glucocorticoid excess through a positive-feedback mechanism","volume":"104","author":"Seki","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2012.05.039","article-title":"Relapsing, remitting hypercortisolism in Cushing's disease due to intratumoral hemorrhages in pituitary microadenoma","volume":"20","author":"Marko","year":"2013","journal-title":"J Clin Neurosci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-005-2961-8","article-title":"Repeated remissions of Cushing's disease due to recurrent infarctions of an ACTH-producing pituitary macroadenoma","volume":"8","author":"Alarifi","year":"2005","journal-title":"Pituitary"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/BF03347559","article-title":"Cyclic Cushing's disease with paradoxical response to dexamethasone","volume":"28","author":"Checchi","year":"2005","journal-title":"J Endocrinol Invest"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.658429","article-title":"Cyclic Cushing's syndrome - a diagnostic challenge","volume":"12","author":"\u015awi\u0105tkowska-Stodulska","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113301","article-title":"Mechanism, diagnosis, and treatment of cyclic Cushing's syndrome: a review","volume":"153","author":"Cai","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab012","article-title":"Pitfalls in performing and interpreting inferior petrosal sinus sampling: personal experience and literature review","volume":"106","author":"Perlman","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3171\/2014.12.FOCUS14780","article-title":"Cyclic Cushing's disease with misleading inferior petrosal sinus sampling results during a trough phase","volume":"38","author":"Bonert","year":"2015","journal-title":"Neurosurg Focus"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1788064\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:36Z","timestamp":1783571016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1788064\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":21,"alternative-id":["10.3389\/fendo.2026.1788064"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1788064","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"article-number":"1788064"}}