{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:08:13Z","timestamp":1772579293236,"version":"3.50.1"},"reference-count":31,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>The relationship between circulating ACTH levels and cortisol secretion in Cushing's disease is not precisely known.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Hypothesis:<\/jats:title>\n                  <jats:p>Chronic ACTH hyperstimulation leads to decreased adrenal potency and is restored after normalization of ACTH secretion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Subjects:<\/jats:title>\n                  <jats:p>Subjects included 20 patients with Cushing's disease, eight patients in long-term remission, and 36 healthy controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcomes:<\/jats:title>\n                  <jats:p>ACTH and cortisol secretion rates and analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Both basal and pulsatile secretion of ACTH and cortisol were increased in patients with active disease but normal in cured patients. ACTH, but not cortisol pulse frequency, was amplified in patients and restored after successful surgical treatment. ACTH EC50, an inverse measure of potency, was higher during pulse onset in Cushing's disease (59 \u00b1 7.4 ng\/liter) than in controls (20 \u00b1 3.7 ng\/liter) (P &amp;lt; 0.0001) and remitted patients after surgery [15 \u00b1 3.2 ng\/liter, P value not significant (NS) vs. controls] and during pulse recovery phases [128 \u00b1 18 (P &amp;lt;0.0001), 70 \u00b1 8.4, and 67 \u00b1 17 ng\/liter (NS vs. controls), respectively]. Efficacy was increased in active disease and normalized after surgical treatment [patients, 38 \u00b1 8.3 nmol\/liter \u00b7 min, vs. controls, 21 \u00b1 2.3 nmol\/liter \u00b7 min (P &amp;lt;0.0001), and cured patients, 15 \u00b1 3.2 nmol\/liter \u00b7 min (NS vs. controls)]. Sensitivity to endogenous ACTH did not differ among the three groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>The adrenal gland in Cushing's disease exhibits decreased responsiveness to submaximal ACTH drive and amplified efficacy, with unchanged sensitivity. These target-gland abnormalities are reversible in long-term remission after pituitary surgery.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2011-1878","type":"journal-article","created":{"date-parts":[[2011,9,15]],"date-time":"2011-09-15T10:02:19Z","timestamp":1316080939000},"page":"3768-3774","source":"Crossref","is-referenced-by-count":10,"title":["Endogenous ACTH Concentration-Cortisol Secretion Dose Analysis Unmasks Decreased ACTH Potency in Cushing's Disease with Restoration after Successful Pituitary Adenomectomy"],"prefix":"10.1210","volume":"96","author":[{"given":"Ferdinand","family":"Roelfsema","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases (F.R.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel M.","family":"Keenan","sequence":"additional","affiliation":[{"name":"Department of Statistics (D.M.K.), University of Virginia, Charlottesville, Virginia 22904"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes D.","family":"Veldhuis","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit (J.D.V.), Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota 55901"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071623444672800_B1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0303-7207(02)00281-2","article-title":"The neurosurgical management of Cushing's disease.","volume":"197","author":"Reitmeyer","year":"2002","journal-title":"Mol Cell Endocrinol"},{"key":"2020071623444672800_B2","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1210\/jcem-40-4-675","article-title":"Relationship of bioassayable and immunoassayable plasma ACTH and cortisol concentrations in normal subjects and in patients with Cushing's 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