{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T20:32:31Z","timestamp":1772915551541,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,5,24]],"date-time":"2004-05-24T00:00:00Z","timestamp":1085356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold><jats:sc>objective\u2002<\/jats:sc><\/jats:bold> As described originally, Nelson's syndrome is characterized by grossly elevated ACTH concentrations, a sellar mass and skin hyperpigmentation emerging in the course of Cushing's disease after bilateral adrenalectomy. No detailed studies have defined whether the mechanisms directing ACTH secretion differ in Nelson's syndrome and untreated Cushing's disease.<\/jats:p><jats:p><jats:bold><jats:sc>patients and methods\u2002<\/jats:sc><\/jats:bold> To address this pathophysiological issue, we studied nine patients fulfilling the criteria of Nelson's syndrome receiving glucocorticoid and mineralocorticoid replacement; nine patients with untreated pituitary\u2010dependent Cushing's disease and nine gender\u2010 and age\u2010matched controls. ACTH release was appraised by monitoring plasma ACTH concentrations in blood samples collected every 10\u00a0min for 24\u00a0h. ACTH secretion rates and endogenous decay were quantified by multiparameter deconvolution analysis. The orderliness of the ACTH release process was delineated by the approximate entropy (ApEn) statistic. Diurnal variation in ACTH secretion was appraised by cosinor analysis.<\/jats:p><jats:p><jats:bold><jats:sc>results\u2002<\/jats:sc><\/jats:bold> Basal ACTH secretion was increased sixfold and pulsatile secretion ninefold in patients with Nelson's syndrome compared with Cushing's disease (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00\u00b701 and <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00\u00b7001, respectively). The increase in pulsatile secretion was due to an eightfold augmentation of burst mass. Event frequency was comparable in both patient groups (32\u00a0\u00b1\u00a01 <jats:italic>vs.<\/jats:italic> 28\u00a0\u00b1\u00a02\u00a0pulses\/24\u00a0h), and higher than in normal controls (22\u00a0\u00b1\u00a01\u00a0pulses\/24\u00a0h, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b70001). Paradoxically, the consistency of subordinate patterns of serial ACTH release, albeit disrupted in active Cushing's disease, was normal in Nelson's syndrome (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7014). Normal ACTH secretory\u2010process regularity in Nelson's syndrome was attributable to a more reproducible (lower ApEn) succession of ACTH secretory\u2010burst mass denoting more uniform amplitude evolution over 24\u00a0h (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7007, Nelson <jats:italic>vs.<\/jats:italic> Cushing). However, the quantifiable regularity of serial interburst intervals (waiting times) was unexpectedly elevated in Nelson's syndrome (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7022). Nelson patients maintained a significant diurnal rhythm in ACTH release, which was marked by a 15\u2010fold greater amplitude (<jats:italic>P<\/jats:italic>\u00a0= 0\u00b70018 <jats:italic>vs.<\/jats:italic> Cushing\u2019s) and a 4\u2010h acrophase (maximum) delay (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7037 <jats:italic>vs.<\/jats:italic> control).<\/jats:p><jats:p><jats:bold><jats:sc>conclusion\u2002<\/jats:sc><\/jats:bold> The present detailed analyses delineate marked ACTH secretory\u2010burst mass amplification and (amplitude\u2010independent) anomalous regularity of successive pulse size and timing in Nelson's syndrome compared with Cushing's disease or controls. We postulate that the foregoing novel distinctions are due to unique tumoural secretory properties, concurrently required glucocorticoid replacement and\/or hypothalamic injury associated with prior radiotherapy in Nelson's syndrome.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2004.02052.x","type":"journal-article","created":{"date-parts":[[2004,5,24]],"date-time":"2004-05-24T11:53:37Z","timestamp":1085399617000},"page":"765-772","source":"Crossref","is-referenced-by-count":23,"title":["Profound amplification of secretory\u2010burst mass and anomalous regularity of ACTH secretory process in patients with Nelson's syndrome compared with Cushing's disease"],"prefix":"10.1111","volume":"60","author":[{"given":"Maarten O.","family":"Van Aken","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto M.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerrit","family":"Van Den Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes A.","family":"Romijn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes D.","family":"Veldhuis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinand","family":"Roelfsema","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,5,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-112-10-738"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1976.tb01959.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00407.2001"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1400192"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.11.4039"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117446"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.81.1.124"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2001.1411a.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02736788"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051624198"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.79.3.887"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2001.01187.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002689910020"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2000.00958.x"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195807242590403"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-62-5-1020"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.6.2297"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0025-5564(94)90056-6"},{"key":"e_1_2_5_20_1","first-page":"E948","article-title":"Hormone pulsatility discrimination via coarse and short time sampling","volume":"277","author":"Pincus S.M.","year":"1999","journal-title":"American Journal of Physiology"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.2.688"},{"key":"e_1_2_5_22_1","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1681\/ASN.V9101832","article-title":"Altered instantaneous and calcium\u2010modulated oscillatory PTH secretion patterns in patients with secondary hyperparathyroidism","volume":"9","author":"Schmitt C.P.","year":"1998","journal-title":"Journal of the American Society of Nephrology"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.79.6.1706"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.12.3750"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1360394"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(92)10028-C"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-9471(06)80028-5"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1380358"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.21.7686"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-71-6-1616"},{"key":"e_1_2_5_31_1","doi-asserted-by":"crossref","first-page":"5554","DOI":"10.1210\/jcem.86.11.8046","article-title":"Corticotropin secretory dynamics in humans under low glucocorticoid feedback","volume":"86","author":"Veldhuis J.D.","year":"2001","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.280.3.R721"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.6.R1975"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(84)90046-7"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2265.2004.02052.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2265.2004.02052.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:10:30Z","timestamp":1697242230000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2265.2004.02052.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,5,24]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1111\/j.1365-2265.2004.02052.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2265.2004.02052.x","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,5,24]]}}}