{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T21:11:01Z","timestamp":1770498661741,"version":"3.49.0"},"reference-count":46,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,1]]},"DOI":"10.1210\/jc.2009-1143","type":"journal-article","created":{"date-parts":[[2009,10,6]],"date-time":"2009-10-06T17:44:55Z","timestamp":1254851095000},"page":"4045-4052","source":"Crossref","is-referenced-by-count":45,"title":["Basal, Pulsatile, Entropic (Patterned), and Spiky (Staccato-like) Properties of ACTH Secretion: Impact of Age, Gender, and Body Mass Index"],"prefix":"10.1210","volume":"94","author":[{"given":"Johannes D.","family":"Veldhuis","sequence":"first","affiliation":[{"name":"Endocrine Research Unit (J.D.V.), Mayo Medical School, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinand","family":"Roelfsema","sequence":"additional","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":"Ali","family":"Iranmanesh","sequence":"additional","affiliation":[{"name":"Endocrine Section (A.I.), Medical Service, Salem Veterans Affairs Medical Center, Salem, Virginia 24153"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard J.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Pacific Behavioral Research Foundation (B.J.C.), Carmel, California 93922"}],"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":"Steven M.","family":"Pincus","sequence":"additional","affiliation":[{"name":"Independent Mathematician (S.M.P.), Guilford, Connecticut 06437"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"key\n\t\t\t\t2019041113475794400_R1","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1210\/endo-118-4-1410","article-title":"Spontaneous and stimulated adrenocorticotropin and vasopressin pulsatile secretion in the pituitary venous effluent of the horse.","volume":"118","author":"Redekopp","year":"1986","journal-title":"Endocrinology"},{"key":"key\n\t\t\t\t2019041113475794400_R2","first-page":"688","article-title":"Patients with Cushing\u2019s disease secrete adrenocorticotropin and cortisol jointly more asynchronously than healthy subjects.","volume":"83","author":"Roelfsema","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R3","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1210\/jcem-71-6-1616","article-title":"Twenty-four hour rhythms in plasma concentrations of adenohypophyseal hormones are generated by distinct amplitude and\/or frequency modulation of underlying pituitary secretory bursts.","volume":"71","author":"Veldhuis","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R4","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","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R5","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/S0024-3205(97)00926-0","article-title":"With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its diurnal amplitude flattens.","volume":"61","author":"Deuschle","year":"1997","journal-title":"Life Sci"},{"key":"key\n\t\t\t\t2019041113475794400_R6","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1530\/eje.0.1440319","article-title":"Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates.","volume":"144","author":"Ferrari","year":"2001","journal-title":"Eur J Endocrinol"},{"key":"key\n\t\t\t\t2019041113475794400_R7","first-page":"2468","article-title":"Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol.","volume":"81","author":"Van Cauter","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R8","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1210\/jcem-71-5-1276","article-title":"Intensive venous sampling paradigms disclose high-frequency ACTH release episodes in normal men.","volume":"71","author":"Iranmanesh","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R9","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1530\/acta.0.1280521","article-title":"Coordinate activation of the corticotropic axis by insulin-induced hypoglycemia: simultaneous estimates of B-endorphin, ACTH, and cortisol secretion and disappearance in normal men.","volume":"128","author":"Iranmanesh","year":"1993","journal-title":"Acta Endocrinol (Copenh)"},{"key":"key\n\t\t\t\t2019041113475794400_R10","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1210\/er.2008-0005","article-title":"Motivations and methods for analyzing pulsatile hormone secretion.","volume":"29","author":"Veldhuis","year":"2008","journal-title":"Endocr Rev"},{"key":"key\n\t\t\t\t2019041113475794400_R11","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.1210\/jc.2005-0830","article-title":"Absence of adrenocorticotropin (ACTH) neurosecretory dysfunction but increased cortisol concentrations and production rates in ACTH-replete adult cancer survivors after cranial irradiation for nonpituitary brain tumors.","volume":"90","author":"Darzy","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R12","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/01.psy.0000161206.55324.8a","article-title":"24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome.","volume":"67","author":"Di Giorgio","year":"2005","journal-title":"Psychosom Med"},{"key":"key\n\t\t\t\t2019041113475794400_R13","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1023\/A:1010318130933","article-title":"The diurnal rhythm of adrenocorticotropic hormone secretion in the assessment of the adequacy of replacement therapy in primary chronic adrenal failure.","volume":"31","author":"Fadeev","year":"2001","journal-title":"Neurosci Behav Physiol"},{"key":"key\n\t\t\t\t2019041113475794400_R14","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1210\/endo.130.5.1572307","article-title":"Evidence of a corticotropin-releasing hormone pulse generator in the macaque hypothalamus.","volume":"130","author":"Mershon","year":"1992","journal-title":"Endocrinology"},{"key":"key\n\t\t\t\t2019041113475794400_R15","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1210\/jcem-69-5-1028","article-title":"Adrenocorticotropin stimulation of aldosterone: prolonged continuous versus pulsatile infusion.","volume":"69","author":"Seely","year":"1989","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R16","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1210\/en.2008-1249","article-title":"Quantifying nonlinear interactions within the hypothalamo-pituitary-adrenal axis in the conscious horse.","volume":"150","author":"Keenan","year":"2009","journal-title":"Endocrinology"},{"key":"key\n\t\t\t\t2019041113475794400_R17","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1073\/pnas.88.6.2297","article-title":"Approximate entropy as a measure of system complexity.","volume":"88","author":"Pincus","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"key\n\t\t\t\t2019041113475794400_R18","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1073\/pnas.051624198","article-title":"A feedback-controlled ensemble model of the stress-responsive hypothalamo-pituitary-adrenal axis.","volume":"98","author":"Keenan","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"key\n\t\t\t\t2019041113475794400_R19","doi-asserted-by":"crossref","first-page":"R721","DOI":"10.1152\/ajpregu.2001.280.3.R721","article-title":"Secretory process regularity monitors neuroendocrine feedback and feedforward signaling strength in humans","volume":"280","author":"Veldhuis","year":"2001","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"key\n\t\t\t\t2019041113475794400_R20","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1210\/jc.2008-1145","article-title":"Thyrotropin secretion by thyrotropinomas is characterized by increased pulse frequency, delayed diurnal rhythm, enhanced basal secretion, spikiness, and disorderliness.","volume":"93","author":"Roelfsema","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R21","first-page":"E6","article-title":"Amplitude modulation of a burst-like mode of cortisol secretion subserves the circadian glucocorticoid rhythm in man","volume":"257","author":"Veldhuis","year":"1989","journal-title":"Am J Physiol"},{"key":"key\n\t\t\t\t2019041113475794400_R22","doi-asserted-by":"crossref","first-page":"R664","DOI":"10.1152\/ajpregu.00195.2003","article-title":"Physiological control of pituitary hormone secretory-burst mass, frequency and waveform: a statistical formulation and analysis","volume":"285","author":"Keenan","year":"2003","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"key\n\t\t\t\t2019041113475794400_R23","first-page":"770","article-title":"Corticosteroid-binding globulin influences kinetic parameters of plasma cortisol transport and clearance.","volume":"80","author":"Bright","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R24","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","article-title":"A new look at the statistical model identification.","volume":"19","author":"Akaike","year":"1974","journal-title":"IEEE Trans Autom Control"},{"key":"key\n\t\t\t\t2019041113475794400_R25","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1073\/pnas.93.5.2083","article-title":"Randomness and degrees of irregularity.","volume":"93","author":"Pincus","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"key\n\t\t\t\t2019041113475794400_R26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/1025389031000111302","article-title":"Gender differences in cardiovascular and hypothalamic-pituitary-adrenal axis responses to psychological stress in healthy older adult men and women.","volume":"6","author":"Traustado\u0301ttir","year":"2003","journal-title":"Stress"},{"key":"key\n\t\t\t\t2019041113475794400_R27","first-page":"1756","article-title":"Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment.","volume":"83","author":"Kudielka","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R28","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.psyneuen.2006.02.003","article-title":"Gender differences in hypothalamic-pituitary-adrenal (HPA) axis reactivity.","volume":"31","author":"Uhart","year":"2006","journal-title":"Psychoneuroendocrinology"},{"key":"key\n\t\t\t\t2019041113475794400_R29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000099832","article-title":"Gender difference in age-related number of corticotropin-releasing hormone-expressing neurons in the human hypothalamic paraventricular nucleus and the role of sex hormones.","volume":"85","author":"Bao","year":"2007","journal-title":"Neuroendocrinology"},{"issue":"Suppl 2","key":"key\n\t\t\t\t2019041113475794400_R30","doi-asserted-by":"crossref","first-page":"S138","DOI":"10.1038\/sj.ijo.0801303","article-title":"Increased response of cortisol and ACTH to corticotrophin releasing hormone in centrally obese men, but not in post-menopausal women","volume":"24","author":"Katz","year":"2000","journal-title":"Int J Obes Relat Metab Disord"},{"key":"key\n\t\t\t\t2019041113475794400_R31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1365-2265.1988.tb01197.x","article-title":"The cortisol response to corticotrophin-releasing factor is blunted in obesity.","volume":"28","author":"Kopelman","year":"1988","journal-title":"Clin Endocrinol (Oxf)"},{"key":"key\n\t\t\t\t2019041113475794400_R32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1055\/s-2001-12625","article-title":"The pituitary response to ovine corticotropin-releasing hormone is enhanced in obese men and correlates with insulin resistance.","volume":"33","author":"Solano","year":"2001","journal-title":"Horm Metab Res"},{"key":"key\n\t\t\t\t2019041113475794400_R33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/oby.2006.30","article-title":"Sex difference in the relationship between the hypothalamic-pituitary-adrenal axis and sex hormones in obesity.","volume":"14","author":"Vicennati","year":"2006","journal-title":"Obesity (Silver Spring)"},{"key":"key\n\t\t\t\t2019041113475794400_R34","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1210\/jcem.87.1.8158","article-title":"Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: a dose-response study.","volume":"87","author":"Pasquali","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R35","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1210\/jc.2008-2054","article-title":"Combined receptor antagonist stimulation of the HPA axis identifies impaired negative feedback sensitivity to cortisol in obese men.","volume":"94","author":"Mattsson","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R36","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1210\/jcem.86.9.7826","article-title":"Resistance to glucocorticoid feedback in obesity.","volume":"86","author":"Jessop","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R37","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.2337\/dc06-1353","article-title":"Massive weight loss decreases corticosteroid-binding globulin levels and increases free cortisol in healthy obese patients: an adaptive phenomenon?","volume":"30","author":"Manco","year":"2007","journal-title":"Diabetes Care"},{"key":"key\n\t\t\t\t2019041113475794400_R38","first-page":"1380","article-title":"Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man.","volume":"83","author":"Boscaro","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R39","doi-asserted-by":"crossref","first-page":"B900","DOI":"10.1093\/gerona\/58.10.B900","article-title":"Mineralocorticoid receptor-mediated inhibition of the hypothalamic-pituitary-adrenal axis in aged humans","volume":"58","author":"Otte","year":"2003","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"key\n\t\t\t\t2019041113475794400_R40","first-page":"545","article-title":"Human glucocorticoid feedback inhibition is reduced in older individuals: evening study.","volume":"86","author":"Wilkinson","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R41","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/0006-3223(94)91214-9","article-title":"Cortisol suppression by dexamethasone in the healthy elderly: effects of age, dexamethasone levels, and cognitive function.","volume":"36","author":"O'Brien","year":"1994","journal-title":"Biol Psychiatry"},{"key":"key\n\t\t\t\t2019041113475794400_R42","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1210\/jcem-73-3-495","article-title":"Spontaneous and glucocorticoid-inhibited adrenocorticotropin hormone and cortisol secretion are similar in healthy young and old men.","volume":"73","author":"Waltman","year":"1991","journal-title":"J Clin Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R43","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.tem.2008.01.009","article-title":"Dissociation of ACTH and glucocorticoids.","volume":"19","author":"Bornstein","year":"2008","journal-title":"Trends Endocrinol Metab"},{"key":"key\n\t\t\t\t2019041113475794400_R44","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1210\/en.2008-0103","article-title":"Corticosterone levels in the brain show a distinct ultradian rhythm but a delayed response to forced swim stress.","volume":"149","author":"Droste","year":"2008","journal-title":"Endocrinology"},{"key":"key\n\t\t\t\t2019041113475794400_R45","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1210\/er.2005-0006","article-title":"Somatotropic and gonadotropic axes linkages in infancy, childhood, and the puberty-adult transition.","volume":"27","author":"Veldhuis","year":"2006","journal-title":"Endocr Rev"},{"key":"key\n\t\t\t\t2019041113475794400_R46","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1210\/edrv-9-1-3","article-title":"Contemporary aspects of discrete peak detection algorithms. I. The paradigm of the luteinizing hormone pulse signal in men.","volume":"9","author":"Urban","year":"1988","journal-title":"Endocr Rev"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/94\/10\/4045\/9061032\/jcem4045.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T01:22:43Z","timestamp":1558574563000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/94\/10\/4045\/2597524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10,1]]},"references-count":46,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2009,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2009-1143","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10,1]]}}}