{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:08:46Z","timestamp":1790874526632,"version":"4.1.0"},"reference-count":40,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FOC"],"published-print":{"date-parts":[[2015,2]]},"abstract":"\n OBJECT<\/jats:title>\n Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and\/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18\u201351 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma \u201cshifted\u201d to a functioning adenoma and then regressed back to a silent form with spontaneous resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9% of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5% of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60\u2013177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.<\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2014.11.focus14679","type":"journal-article","created":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T03:40:53Z","timestamp":1422762053000},"page":"E15","source":"Crossref","is-referenced-by-count":28,"title":["ACTH adenomas transforming their clinical expression: report of 5 cases"],"prefix":"10.3171","volume":"38","author":[{"given":"Matteo","family":"Zoli","sequence":"first","affiliation":[{"name":"Center of Surgery for Pituitary Tumors and Endoscopic Skull Base Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Faustini-Fustini","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Mazzatenta","sequence":"additional","affiliation":[{"name":"Center of Surgery for Pituitary Tumors and Endoscopic Skull Base Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Marucci","sequence":"additional","affiliation":[{"name":"Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Section of Pathology \u201cM. Malpighi,\u201d Bellaria Hospital, University of Bologna, Bologna;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"De Carlo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Padova University, Padova;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Bacci","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, IRCCS Istituto delle Scienze Neurologiche di Bologna;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Pasquini","sequence":"additional","affiliation":[{"name":"ENT Department, Azienda USL, Bologna, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lanzino","sequence":"additional","affiliation":[{"name":"Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Frank","sequence":"additional","affiliation":[{"name":"Center of Surgery for Pituitary Tumors and Endoscopic Skull Base Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-focus14679","series-title":"J Endocrinol Invest","first-page":"443","article-title":"The silent corticotropinoma: is clinical diagnosis possible?","volume":"15","author":"Ambrosi","year":"1992"},{"key":"b2-focus14679","series-title":"Br J Neurosurg","first-page":"38","article-title":"A spectrum of behaviour in silent corticotroph pituitary adenomas","volume":"19","author":"Baldeweg","year":"2005"},{"key":"b3-focus14679","series-title":"Endocr Pract","first-page":"463","article-title":"Transformation of a pituitary macroadenoma into to a corticotropin-secreting carcinoma over 16 years","volume":"13","author":"Brown","year":"2007"},{"key":"b4-focus14679","series-title":"Arch Intern Med","first-page":"840","article-title":"Desmopressin test in occult eutopic corticotroph microadenoma","volume":"162","author":"Chiodera","year":"2002"},{"key":"b5-focus14679","series-title":"Clin Endocrinol (Oxf)","first-page":"648","article-title":"Silent corticotroph adenomas have unique recurrence characteristics compared with other nonfunctioning pituitary adenomas","volume":"72","author":"Cho","year":"2010"},{"key":"b6-focus14679","series-title":"Aust N Z J Med","first-page":"249","article-title":"The development of Cushing's syndrome from a previously silent pituitary tumour","volume":"17","author":"Cooper","year":"1987"},{"key":"b7-focus14679","series-title":"Arch Intern Med","first-page":"2377","article-title":"Late complications in remission from Cushing disease. Recurrence of tumor with reinfarction or transformation into a silent adenoma","volume":"157","author":"Dickstein","year":"1997"},{"key":"b8-focus14679","series-title":"Arq Bras Endocrinol Metabol","first-page":"324","article-title":"A rare case of Cushing syndrome by cyclic ectopic-ACTH","volume":"56","author":"Farage","year":"2012"},{"key":"b9-focus14679","series-title":"Am J Pathol","first-page":"617","article-title":"Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural study","volume":"98","author":"Horvath","year":"1980"},{"key":"b10-focus14679","series-title":"Neurosurgery","first-page":"296","article-title":"Silent corticotroph adenomas: Emory University cohort and comparison with ACTH-negative nonfunctioning pituitary adenomas","volume":"71","author":"Ioachimescu","year":"2012"},{"key":"b11-focus14679","series-title":"Arch Intern Med","first-page":"251","article-title":"Spontaneous remission in Cushing's disease","volume":"153","author":"Ishibashi","year":"1993"},{"key":"b12-focus14679","series-title":"Am J Med","first-page":"492","article-title":"Silent corticotroph cell adenoma with lysosomal accumulation and crinophagy. A distinct clinicopathologic entity","volume":"64","author":"Kovacs","year":"1978"},{"key":"b13-focus14679","series-title":"Neurosurgery","first-page":"E144","article-title":"Silent or subclinical corticotroph pituitary macroadenoma transforming into Cushing disease: 11-year follow-up","volume":"72","author":"Melcescu","year":"2013"},{"key":"b14-focus14679","series-title":"Eur J Endocrinol","first-page":"35","article-title":"Clinical, hormonal and molecular characterization of pituitary ACTH adenomas without (silent corticotroph adenomas) and with Cushing's disease","volume":"163","author":"Raverot","year":"2010"},{"key":"b15-focus14679","series-title":"Endocr Pathol","first-page":"191","article-title":"Cushing's disease arising from a clinically nonfunctioning pituitary adenoma","volume":"17","author":"Salgado","year":"2006"},{"key":"b16-focus14679","series-title":"Pituitary","first-page":"117","article-title":"Metamorphosis of a non-functioning pituitary adenoma to Cushing's disease","volume":"3","author":"Tan","year":"2000"},{"key":"b17-focus14679","series-title":"Clin Endocrinol (Oxf)","first-page":"147","article-title":"Pituitary Cushing's disease arising from a previously non-functional corticotrophic chromophobe adenoma","volume":"22","author":"Vaughan","year":"1985"},{"issue":"3","key":"b18-focus14679","series-title":"Neurosurg Focus","first-page":"E4","article-title":"Cyclic Cushing syndrome: definitions and treatment implications","volume":"23","author":"Velez","year":"2007"},{"key":"b19-focus14679","series-title":"Nat Rev Endocrinol","first-page":"431","article-title":"The postoperative monitoring of nonfunctioning pituitary adenomas","volume":"7","author":"Wass","year":"2011"},{"key":"b20-focus14679","series-title":"Neuropathology","first-page":"288","article-title":"A case of non-functioning pituitary adenoma with Cushing's syndrome upon recurrence","volume":"21","author":"Yokoyama","year":"2001"},{"key":"b1-focus14679","series-title":"J Endocrinol Invest","first-page":"443","article-title":"The silent corticotropinoma: is clinical diagnosis possible?","volume":"15","author":"Ambrosi","year":"1992"},{"key":"b2-focus14679","series-title":"Br J Neurosurg","first-page":"38","article-title":"A spectrum of behaviour in silent corticotroph pituitary adenomas","volume":"19","author":"Baldeweg","year":"2005"},{"key":"b3-focus14679","series-title":"Endocr Pract","first-page":"463","article-title":"Transformation of a pituitary macroadenoma into to a corticotropin-secreting carcinoma over 16 years","volume":"13","author":"Brown","year":"2007"},{"key":"b4-focus14679","series-title":"Arch Intern Med","first-page":"840","article-title":"Desmopressin test in occult eutopic corticotroph microadenoma","volume":"162","author":"Chiodera","year":"2002"},{"key":"b5-focus14679","series-title":"Clin Endocrinol (Oxf)","first-page":"648","article-title":"Silent corticotroph adenomas have unique recurrence characteristics compared with other nonfunctioning pituitary adenomas","volume":"72","author":"Cho","year":"2010"},{"key":"b6-focus14679","series-title":"Aust N Z J Med","first-page":"249","article-title":"The development of Cushing's syndrome from a previously silent pituitary tumour","volume":"17","author":"Cooper","year":"1987"},{"key":"b7-focus14679","series-title":"Arch Intern Med","first-page":"2377","article-title":"Late complications in remission from Cushing disease. 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