{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:47:41Z","timestamp":1791380861755,"version":"4.3.3"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"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><jats:title>Purpose<\/jats:title><jats:p>Cushing\u2019s disease is the most common cause of endogenous hypercortisolemia due to a corticotroph pituitary tumor. Up-to-date there is no reliable biomarker of invasiveness among corticotroph tumors, while it is well established in the literature that sparsely granulated somatotroph tumors are characterized by poorer prognosis. The aim of the study was to correlate multiple data including clinical, biochemical, radiological, and pathological findings (including granulation pattern) as well as immediate post-operative remission status among patients operated on due to corticotroph tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled all patients consecutively operated on for planned transsphenoidal neurosurgery due to corticotroph PitNETs in years 2010\u20132018. We excluded from analysis silent corticotroph tumors, plurihormonal PitNETs, and the Crooke\u2019s cell adenomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We recorded 348 hormonally active corticotroph PitNETs. The results of the analysis showed the female predominance 79.88% (n = 278), with the mean age of Cushing\u2019s disease occurrence 43.27 years of age. The mean time from the first signs and symptoms to the operation was 2 years. The women were diagnosed earlier (20\u201340 years of age<jats:italic>vs.<\/jats:italic>50\u201360 years of age among men). We performed a detailed analysis of 277 cases classified by granularity pattern as DG or SG corticotroph PitNETs. Densely granulated tumors (DG) occurred four times more frequently than sparsely granulated (SG) (n = 225<jats:italic>vs<\/jats:italic>. n = 52), at similar age (mean 42.94; median 40<jats:italic>vs.<\/jats:italic>mean 45.46; median 45.5; p = 0.3896), but were characterized by lower Knosp\u2019s scale grades (p = 0.0147*), smaller preoperative tumors\u2019 volumes measured at MRI, and more commonly exhibited lower Ki-67 labeling index (&amp;lt;3%) (p = 0.0168*). What is more, DG adenomas more frequently achieved an immediate remission status (measured as postoperative cortisol concentration &amp;lt;2 \u00b5g\/dl; p = 0.0180*), and the mean postoperative cortisol concentration in DG group was lower than in SG group (mean 5.375 \u00b5g\/dl<jats:italic>vs<\/jats:italic>. 10.47 \u00b5g\/dl; median 2.49 \u00b5g\/dl<jats:italic>vs<\/jats:italic>. 6.52 \u00b5g\/dl; p = 0.0028**).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study indicates that DG corticotroph adenomas occurred at younger age, more commonly were microadenomas as compared to SG tumors, less frequently had invasive features in comparison to SG corticotroph adenomas (p = 0.0019**), and more commonly achieved an immediate postsurgical hormonal remission (p = 0.0180*). We highlight the need for an accurate differentiation of DG and SG subtypes in the pathomorphological diagnosis of corticotropic tumors, especially in invasive PitNETs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.672178","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T18:28:23Z","timestamp":1622485703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Clinical, Biological, Radiological Pathological and Immediate Post-Operative Remission of Sparsely and Densely Granulated Corticotroph Pituitary Tumors: A Retrospective Study of a Cohort of 277 Patients With Cushing\u2019s Disease"],"prefix":"10.3389","volume":"12","author":[{"given":"Beata","family":"Rak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Maksymowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"P\u0119kul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Zieli\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-0984-8","article-title":"Cushing\u2019s Disease: The Burden of Illness","volume":"56","author":"Pivonello","year":"2017","journal-title":"Endocrine"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.1.7093","article-title":"Incidence and Late Prognosis of Cushing\u2019s Syndrome: A Population-Based Study","volume":"86","author":"Lindholm","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1994.tb02486.x","article-title":"Morbidity and Mortality in Cushing\u2019s Disease: An Epidemiological Approach","volume":"40","author":"Etxabe","year":"1994","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68699-6","article-title":"Cushing\u2019s Syndrome","volume":"367","author":"Newell-Price","year":"2006","journal-title":"Lancet"},{"key":"B5","article-title":"Cushing\u2019s Syndrome: Epidemiology and Developments in Disease Management","volume":"7","author":"Sharma","year":"2015","journal-title":"Clin Epidemiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2007.03.005","article-title":"Paediatric Cushing\u2019s Syndrome: Epidemiology, Investigation and Therapeutic Advances","volume":"18","author":"Storr","year":"2007","journal-title":"Trends Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031531","article-title":"Prepubertal Cushing\u2019s Disease is More Common in Males, But There Is No Increase in Severity at Diagnosis","volume":"89","author":"Storr","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199409083311002","article-title":"Cushing\u2019s Syndrome in Children and Adolescents. 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