{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:56:16Z","timestamp":1792828576596,"version":"4.5.0"},"reference-count":36,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,9,1]]},"abstract":"<jats:p>OBJECTIVE. Endogenous Cushing syndrome in children is a rare disorder that is most frequently caused by pituitary or adrenocortical tumors. Diagnostic criteria have generally been derived from studies of adult patients despite significant differences in both the physiology of the hypothalamic-pituitary-adrenal axis and the epidemiology of Cushing syndrome in childhood. The purpose of this study was to identify the tests that most reliably and efficiently diagnose pituitary or adrenal tumors in a large cohort of pediatric patients with Cushing syndrome.<\/jats:p>\n                  <jats:p>METHODS. A retrospective review of clinical data of children who were referred to a tertiary care center for evaluation for Cushing syndrome during the years 1997 to 2005 was conducted. A total of 125 consecutive children were studied retrospectively; 105 were found to have Cushing syndrome, which was confirmed histologically; and 20 children who did not have Cushing syndrome or any other endocrinopathy served as the control group. The following tests were performed in all children: midnight and morning cortisol, corticotropin hormone, urinary free cortisol and 17-hydroxycorticosteroid levels, ovine corticotropin-releasing hormone stimulation test, and overnight high-dosage dexamethasone suppression test. Imaging of the pituitary and adrenal glands was also obtained. The main outcome measure was the sensitivity of these parameters for the diagnosis and differential diagnosis of Cushing syndrome at 100% specificity.<\/jats:p>\n                  <jats:p>RESULTS. A midnight cortisol value of \u22654.4 \u03bcg\/dL confirmed the diagnosis of Cushing syndrome in almost all children, with a sensitivity of 99% and a specificity of 100%. Suppression of morning cortisol levels &amp;gt;20% in response to an overnight, high-dosage dexamethasone test excluded all patients with adrenal tumors and identified almost all patients with pituitary tumors (sensitivity: 97.5%; specificity: 100%).<\/jats:p>\n                  <jats:p>CONCLUSIONS. Our study suggests that among children who were referred for the evaluation of possible Cushing syndrome, a single cortisol value at midnight followed by overnight high-dosage dexamethasone test led to rapid and accurate confirmation and diagnostic differentiation, respectively, of hypercortisolemia caused by pituitary and adrenal tumors.<\/jats:p>","DOI":"10.1542\/peds.2006-2402","type":"journal-article","created":{"date-parts":[[2007,8,13]],"date-time":"2007-08-13T20:39:54Z","timestamp":1187037594000},"page":"e575-e586","source":"Crossref","is-referenced-by-count":136,"title":["Diagnostic Tests for Children Who Are Referred for the Investigation of Cushing Syndrome"],"prefix":"10.1542","volume":"120","author":[{"given":"Dalia L.","family":"Batista","sequence":"first","affiliation":[{"name":"Section on Endocrinology and Genetics, Developmental Endocrinology Branch, and Pediatric Endocrinology Inter-Institute Training Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehan","family":"Riar","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics, Developmental Endocrinology Branch, and Pediatric Endocrinology Inter-Institute Training Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meg","family":"Keil","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics, Developmental Endocrinology Branch, and Pediatric Endocrinology Inter-Institute Training Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine A.","family":"Stratakis","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics, Developmental Endocrinology Branch, and Pediatric Endocrinology Inter-Institute Training Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2007,9,1]]},"reference":[{"key":"2021120902253596700_R1","doi-asserted-by":"crossref","unstructured":"Lindholm JF, Juul S, Jorgensen JO, et al. 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J Clin Endocrinol Metab.\u20082003;88:5593\u20135602","DOI":"10.1210\/jc.2003-030871"},{"key":"2021120902253596700_R5","doi-asserted-by":"crossref","unstructured":"Newell-Price JF, Trainer PF, Besser MF, Grossman AB. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states. Endocr Rev.\u20081998;19:647\u2013672","DOI":"10.1210\/edrv.19.5.0346"},{"key":"2021120902253596700_R6","doi-asserted-by":"crossref","unstructured":"Nieman LK. Diagnostic tests for Cushing's syndrome. Ann N Y Acad Sci.\u20082002;970:112\u2013118","DOI":"10.1111\/j.1749-6632.2002.tb04417.x"},{"key":"2021120902253596700_R7","doi-asserted-by":"crossref","unstructured":"Boscaro MF, Barzon LF, Fallo FF, Sonino N. Cushing's syndrome. Lancet.\u20082001;357:783\u2013791","DOI":"10.1016\/S0140-6736(00)04172-6"},{"key":"2021120902253596700_R8","doi-asserted-by":"crossref","unstructured":"Normann T, Hanven J, Mjolnerod O. Cushing syndrome in an infant associated with neuroblastoma in two ectopic adrenal glands. J Pediatr Surg.\u20081971;6:169\u2013175","DOI":"10.1016\/0022-3468(71)90313-7"},{"key":"2021120902253596700_R9","doi-asserted-by":"crossref","unstructured":"Arioglu E, Doppman J, Gomes M, et al. Cushing's syndrome caused by corticotropin secretion by pulmonary tumorlets. N Engl J Med.\u20081998;339:883\u2013886","DOI":"10.1056\/NEJM199809243391304"},{"key":"2021120902253596700_R10","doi-asserted-by":"crossref","unstructured":"Stratakis CA. Adrenocortical tumors, primary pigmented adrenocortical disease (PPNAD)\/Carney complex, and other bilateral hyperplasias: the NIH studies. Horm Metab Res.\u20082007;39:467\u2013473","DOI":"10.1055\/s-2007-981477"},{"key":"2021120902253596700_R11","doi-asserted-by":"crossref","unstructured":"Gunther DF, Bourdeau I, Matyakhina L, et al. 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