{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:37:19Z","timestamp":1787312239136,"version":"build-2736575974"},"reference-count":30,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,10,1]]},"abstract":"<jats:p>Context: The Dutch neonatal congenital hypothyroidism (CH) screening program detects infants with CH of central origin (CH-C). These infants have a high likelihood of multiple pituitary hormone deficiencies. ACTH deficiency especially poses an additional risk for brain damage and may be fatal.<\/jats:p>\n                  <jats:p>Objective: Our objective was to evaluate different tools for assessment of the integrity of the hypothalamus-pituitary-adrenocortex (HPA) axis in young infants, aiming for a strategy for reliable and timely diagnosis.<\/jats:p>\n                  <jats:p>Design, Setting: This is a Dutch nationwide prospective study (enrollment 1994\u20131996). Patients were included if neonatal CH screening results were indicative of CH-C and HPA axis function could be tested within 6 months of birth.<\/jats:p>\n                  <jats:p>Patients: Nine male and three female infants with CH-C and four infants with false-positive screening results or transient hypothyroidism were included in the study.<\/jats:p>\n                  <jats:p>Main Outcome Measures: CRH test results, multiple cortisol plasma concentrations, and cortisol excretion in 24-h urine were measured.<\/jats:p>\n                  <jats:p>Results: Six (50%) of the CH-C patients had abnormal CRH test results. Three of them had discordant test results: impaired increase of plasma cortisol in response to CRH, despite substantial increase of plasma ACTH. The other three infants, with concordant impaired responses of both ACTH and cortisol to CRH, had a very low urinary cortisol excretion in comparison with the subjects with normal CRH test results.<\/jats:p>\n                  <jats:p>Conclusions: The CRH test proves to be a fast and reliable tool in the assessment of HPA axis (dys)function. It enables timely diagnosis in (asymptomatic) neonates at risk for serious morbidity and mortality. The discordant response type, which has not been described before, may be an early phase of HPA axis dysfunction. Alternatively, patients with this response type may constitute a separate pathogenetic subset of HPA axis-deficient patients.<\/jats:p>","DOI":"10.1210\/jc.2008-0492","type":"journal-article","created":{"date-parts":[[2008,7,22]],"date-time":"2008-07-22T20:34:27Z","timestamp":1216758867000},"page":"3794-3803","source":"Crossref","is-referenced-by-count":8,"title":["Role of Corticotropin-Releasing Hormone Testing in Assessment of Hypothalamic-Pituitary-Adrenal Axis Function in Infants with Congenital Central Hypothyroidism"],"prefix":"10.1210","volume":"93","author":[{"given":"David A.","family":"van Tijn","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J. M.","family":"de Vijlder","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vulsma","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614015731000_R1","first-page":"1691","article-title":"Eternal vigilance\u2013mortality in children with growth hormone deficiency.","volume":"81","author":"Hintz","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1001\/archopht.1997.01100150068011","article-title":"Sudden death in septo-optic dysplasia. Report of 5 cases.","volume":"115","author":"Brodsky","year":"1997","journal-title":"Arch Ophthalmol"},{"key":"2020071614015731000_R3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s001340050021","article-title":"Adrenal crisis presenting as hypoglycemic coma.","volume":"26","author":"Fischer","year":"2000","journal-title":"Intensive Care Med"},{"key":"2020071614015731000_R4","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1210\/jc.2004-1300","article-title":"Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations.","volume":"90","author":"Vallette-Kasic","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R5","first-page":"343","article-title":"Detection and classification of congenital thyrotropin deficiency in The Netherlands","author":"Vulsma","year":"1989","journal-title":"In: Drexhage HA, de Vijlder JJM, Wiersinga WM, eds. The thyroid gland, environment, and autoimmunity: proceedings of the International Symposium on Thyroid Gland, Environment, and Autoimmunity, Amsterdam, 18\u201320 October l989. Amsterdam: Excerpta Medica;"},{"key":"2020071614015731000_R6","author":"Vulsma","year":"1991"},{"key":"2020071614015731000_R7","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1542\/peds.2004-2162","article-title":"Clinical effectiveness and cost-effectiveness of the use of the thyroxine\/thyroxine-binding globulin ratio to detect congenital hypothyroidism of thyroidal and central origin in a neonatal screening program.","volume":"116","author":"Lanting","year":"2005","journal-title":"Pediatrics"},{"key":"2020071614015731000_R8","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1210\/jc.2004-2444","article-title":"Neonatal detection of congenital hypothyroidism of central origin.","volume":"90","author":"Van Tijn","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R9","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1210\/jc.2005-0851","article-title":"Next generation newborn screening for congenital hypothyroidism?","volume":"90","author":"Fisher","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0378-3782(03)00074-4","article-title":"Development of cortisol circadian rhythm in infancy.","volume":"73","author":"De Weerth","year":"2003","journal-title":"Early Hum Dev"},{"key":"2020071614015731000_R11","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3171\/jns.1979.51.3.0271","article-title":"Clinical endocrinological approach to hypothalamic-pituitary disease.","volume":"51","author":"Abboud","year":"1979","journal-title":"J Neurosurg"},{"key":"2020071614015731000_R12","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1210\/jcem-19-8-875","article-title":"Clinical application of a new test of pituitary reserve.","volume":"19","author":"Liddle","year":"1959","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1046\/j.1365-2265.2000.01093.x","article-title":"The insulin hypoglycaemia and overnight metyrapone test in the assessment of the hypothalamic-pituitary-adrenal axis following pituitary surgery.","volume":"53","author":"Courtney","year":"2000","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071614015731000_R14","first-page":"248","article-title":"Adrenal function tests","author":"Forest","year":"1992","journal-title":"In: Ranke MB, Albertsson-Wikland K, eds. Functional endocrinologic diagnostics in children and adolescents. 1st ed. Mannheim, Germany: J & J Verlag;"},{"key":"2020071614015731000_R15","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1530\/eje.1.01911","article-title":"Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests.","volume":"152","author":"Maghnie","year":"2005","journal-title":"Eur J Endocrinol"},{"key":"2020071614015731000_R16","first-page":"4592","article-title":"Adrenocorticotropin and corticotropin-releasing hormone tests in preterm infants.","volume":"85","author":"Karlsson","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R17","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1210\/jc.2006-2656","article-title":"Role of the thyrotropin-releasing hormone stimulation test in diagnosis of congenital central hypothyroidism in infants.","volume":"93","author":"Van Tijn","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R18","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1210\/jc.2006-0689","article-title":"Early assessment of hypothalamic-pituitary-gonadal function in patients with congenital hypothyroidism of central origin.","volume":"92","author":"Van Tijn","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1046\/j.1365-2265.2001.01185.x","article-title":"Hypothalamo-pituitary-adrenal axis testing: nothing is sacred and caution in interpretation is needed.","volume":"54","author":"Dickstein","year":"2001","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071614015731000_R20","first-page":"525","article-title":"Establishment of reference ranges for cortisol in neonates, infants, children and adolescents.","volume":"31","author":"Jonetz-Mentzel","year":"1993","journal-title":"Eur J Clin Chem Clin Biochem"},{"key":"2020071614015731000_R21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0140-6736(88)91001-X","article-title":"TSH-receptor antibodies in mothers with Graves\u2019 disease and outcome in their offspring.","volume":"1","author":"Matsuura","year":"1988","journal-title":"Lancet"},{"key":"2020071614015731000_R22","doi-asserted-by":"crossref","first-page":"5851","DOI":"10.1210\/jc.2003-030665","article-title":"Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed.","volume":"88","author":"Kempers","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1365-2265.1984.tb00061.x","article-title":"Corticotrophin releasing hormone: responses in normal subjects and patients with disorders of the hypothalamus and pituitary.","volume":"20","author":"Lytras","year":"1984","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071614015731000_R24","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1210\/jcem-59-6-1103","article-title":"Human corticotropin-releasing factor in man: pharmacokinetic properties and dose-response of plasma adrenocorticotropin and cortisol secretion.","volume":"59","author":"Schu\u0308rmeyer","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R25","first-page":"1545","article-title":"Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1\/POU1F1 gene.","volume":"86","author":"Hendriks-Stegeman","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"issue":"Suppl 3","key":"2020071614015731000_R26","doi-asserted-by":"crossref","first-page":"U25","DOI":"10.1530\/eje.0.151u025","article-title":"Role of thyroid hormone during early brain development","volume":"151","author":"Morreale de Escobar","year":"2004","journal-title":"Eur J Endocrinol"},{"key":"2020071614015731000_R27","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1210\/jc.2005-1209","article-title":"Intellectual and motor development of young adults with congenital hypothyroidism diagnosed by neonatal screening.","volume":"91","author":"Kempers","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R28","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1210\/jc.2006-1538","article-title":"Neonatal screening for congenital hypothyroidism in The Netherlands: cognitive and motor outcome at 10 years of age.","volume":"92","author":"Kempers","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614015731000_R29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1530\/eje.1.01797","article-title":"Genetic control of growth.","volume":"152","author":"Mullis","year":"2005","journal-title":"Eur J Endocrinol"},{"key":"2020071614015731000_R30","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1055\/s-2007-979000","article-title":"Reproducibility of growth hormone and cortisol responses to the insulin tolerance test and the short ACTH test in normal adults.","volume":"29","author":"Vestgaard","year":"1997","journal-title":"Horm Metabolic Res"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/10\/3794\/9053651\/jcem3794.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/10\/3794\/9053651\/jcem3794.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T21:13:32Z","timestamp":1594934012000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/93\/10\/3794\/2627309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,1]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2008-0492","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,1]]}}}