{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:08:44Z","timestamp":1788322124862,"version":"build-2803163510"},"reference-count":32,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND AND OBJECTIVE:<\/jats:title>\n                  <jats:p>Hypothalamic-pituitary-adrenal axis suppression (HPAS) when treating children with corticosteroids is thought to be rare. Our objective was to determine the prevalence of and predictive factors for various degrees of HPAS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS:<\/jats:title>\n                  <jats:p>Clinical features of HPAS, doses, adherence, asthma score, and lung functions were recorded in 143 asthmatic children. The overnight metyrapone test was performed if morning cortisol was &amp;gt;83 nmol\/L. Spearman correlations coefficients (r) were calculated between 3 postmetyrapone outcomes and each continuous variable. A multiple linear regression model of \u221apostmetyrapone adrenocorticotropic hormone (ACTH) and a logistic regression model for HPAS were developed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS:<\/jats:title>\n                  <jats:p>Hypocortisolemia was seen in 6.1% (1.8\u201310.5), hypothalamic-pituitary suppression (HPS) in 22.2% (14.5\u201329.9), adrenal suppression in 32.3% (23.7\u201340.9), HPAS in 16.3% (9.3\u201323.3), and any hypothalamic-pituitary-adrenal axis dysfunction in 65.1% (56.5\u201372.9). Log daily nasal steroid (NS) dose\/m2 was associated with HPAS in the logistic regression model (odds ratio = 3.7 [95% confidence interval: 1.1\u201313.6]). Daily inhaled corticosteroids (ICSs) + NS dose\/m2 predicted HPAS in the univariate logistic regression model (P = .038). Forced expiratory volume in 1 second\/forced vital capacity &amp;lt;80% was associated with HPAS (odds ratio = 4.1 [95% confidence interval: 1.0\u201314.8]). Daily ICS + NS\/m2 dose was correlated with the postmetyrapone ACTH (r = \u22120.29, P &amp;lt; .001). BMI (P = .048) and percent adherence to ICS (P &amp;lt; .001) and NS (P = .002) were predictive of \u221apostmetyrapone ACTH (R2 = .176).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS:<\/jats:title>\n                  <jats:p>Two-thirds of children on corticosteroids may have hypothalamic-pituitary-adrenal axis dysfunction. In one-third, central function had recovered but adrenal suppression persisted. Predictive factors for HPAS are NS use, BMI, and adherence to ICS and NS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.2012-1147","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T10:52:14Z","timestamp":1352803934000},"page":"e1512-e1519","source":"Crossref","is-referenced-by-count":73,"title":["Hypothalamic-Pituitary-Adrenal Axis Suppression in Asthmatic School Children"],"prefix":"10.1542","volume":"130","author":[{"given":"Ekkehard Werner","family":"Z\u00f6llner","sequence":"first","affiliation":[{"name":"Paediatric Endocrine Unit, Tygerberg Children\u2019s Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J.","family":"Lombard","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Medical Research Council, Cape Town, South Africa; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ushma","family":"Galal","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Medical Research Council, Cape Town, South Africa; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Stephen","family":"Hough","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvis M.","family":"Irusen","sequence":"additional","affiliation":[{"name":"Pulmonology Division, Tygerberg Hospital, University of Stellenbosch, Cape Town, South Africa;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Allergy Unit, Red Cross Children\u2019s Hospital, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2012,12,1]]},"reference":[{"issue":"4 pt 2","key":"2021120823555704100_B1","doi-asserted-by":"crossref","first-page":"S447","DOI":"10.1016\/S0091-6749(98)70157-5","article-title":"Clinical relevance of inhaled corticosteroids and HPA axis suppression.","volume":"101","author":"Dluhy","year":"1998","journal-title":"J Allergy Clin Immunol"},{"issue":"4","key":"2021120823555704100_B2","first-page":"333","article-title":"Commentary: Symptomatic adrenal insufficiency during inhaled corticosteroid treatment.","volume":"85","author":"Russel","year":"2001","journal-title":"Arch Dis Child"},{"key":"2021120823555704100_B3","first-page":"28s","article-title":"Safety of treatment.","volume":"21","author":"Bisgaard","year":"1996","journal-title":"Eur Respir J Suppl"},{"issue":"1","key":"2021120823555704100_B4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1515\/JPEM.2002.15.1.5","article-title":"Effects of inhaled or nasal glucocorticosteroids on adrenal function and growth.","volume":"15","author":"Sizonenko","year":"2002","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2021120823555704100_B5","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1067\/mai.2001.115564","article-title":"Effects of intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis in children.","volume":"108","author":"Boner","year":"2001","journal-title":"J Allergy Clin Immunol"},{"issue":"5","key":"2021120823555704100_B6","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1159\/000216193","article-title":"Intranasal corticosteroids and adrenal suppression.","volume":"16","author":"Bruni","year":"2009","journal-title":"Neuroimmunomodulation"},{"issue":"5","key":"2021120823555704100_B7","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1399-3038.2007.00540.x","article-title":"Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled corticosteroids: part 1. Which test should be used?","volume":"18","author":"Z\u00f6llner","year":"2007","journal-title":"Pediatr Allergy Immunol"},{"issue":"6","key":"2021120823555704100_B8","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1399-3038.2007.00539.x","article-title":"Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled corticosteroids (Part 2)\u2014the risk as determined by gold standard adrenal function tests: a systematic review.","volume":"18","author":"Z\u00f6llner","year":"2007","journal-title":"Pediatr Allergy Immunol"},{"issue":"4","key":"2021120823555704100_B9","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/S0022-3476(82)80781-6","article-title":"Adrenal effects of beclomethasone inhalation therapy in asthmatic children.","volume":"100","author":"Vaz","year":"1982","journal-title":"J Pediatr"},{"issue":"7\u20138","key":"2021120823555704100_B10","first-page":"529","article-title":"Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids\u2014more common than expected?","volume":"24","author":"Z\u00f6llner","year":"2011","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2021120823555704100_B11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1210\/jcem-25-1-11","article-title":"Natural history of pituitary-adrenal recovery following long-term suppression with corticosteroids.","volume":"25","author":"Graber","year":"1965","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2021120823555704100_B12","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1001\/jama.1979.03290380027021","article-title":"Metyrapone test with adrenocorticotrophic levels. Separating primary from secondary adrenal insufficiency.","volume":"241","author":"Dolman","year":"1979","journal-title":"JAMA"},{"issue":"1","key":"2021120823555704100_B13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1055\/s-0029-1211262","article-title":"Pituitary function tests: comparison of ACTH and 11-deoxy-cortisol responses in the metyrapone test and with the insulin hypoglycemia test.","volume":"102","author":"Steiner","year":"1994","journal-title":"Exp Clin Endocrinol"},{"key":"2021120823555704100_B14","first-page":"74","article-title":"Topical and systemic glucocorticoid potencies of budesonide, beclomethasone dipropionate and prednisolone in man.","volume":"122","author":"Johansson","year":"1982","journal-title":"Eur J Respir Dis Suppl"},{"key":"2021120823555704100_B15"},{"issue":"1","key":"2021120823555704100_B16","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2165\/00128071-200203010-00005","article-title":"New and established topical corticosteroids in dermatology: clinical pharmacology and therapeutic use.","volume":"3","author":"Brazzini","year":"2002","journal-title":"Am J Clin Dermatol"},{"issue":"4","key":"2021120823555704100_B17","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.rmed.2005.08.012","article-title":"Identifying \u2018well-controlled\u2019 and \u2018not well-controlled\u2019 asthma using the Asthma Control Questionnaire.","volume":"100","author":"Juniper","year":"2006","journal-title":"Respir Med"},{"issue":"6","key":"2021120823555704100_B18","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/j.1365-2265.1979.tb02119.x","article-title":"The short metyrapone test: comparison of the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia.","volume":"10","author":"Staub","year":"1979","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"5","key":"2021120823555704100_B19","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1365-2265.1994.tb03011.x","article-title":"The overnight single-dose metyrapone test is a simple and reliable index of the hypothalamic-pituitary-adrenal axis.","volume":"40","author":"Fiad","year":"1994","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"12","key":"2021120823555704100_B20","doi-asserted-by":"crossref","first-page":"5470","DOI":"10.1210\/jc.2001-011959","article-title":"Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function.","volume":"87","author":"Berneis","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2021120823555704100_B21","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/S0022-3476(05)80128-3","article-title":"Cortisol production rate in childhood and adolescence.","volume":"117","author":"Linder","year":"1990","journal-title":"J Pediatr"},{"issue":"11","key":"2021120823555704100_B22","first-page":"435","article-title":"Establishment of reference values for endocrine tests. Part IV: Adrenal insufficiency.","volume":"63","author":"Endert","year":"2005","journal-title":"Neth J Med"},{"key":"2021120823555704100_B23","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1749-6632.2010.05902.x","article-title":"Molecular genetics of hypothalamic-pituitary-adrenal axis activity and function.","volume":"1220","author":"Mormede","year":"2011","journal-title":"Ann N Y Acad Sci"},{"issue":"5","key":"2021120823555704100_B24","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1159\/000216192","article-title":"Single nucleotide polymorphisms related to HPA axis reactivity.","volume":"16","author":"Derijk","year":"2009","journal-title":"Neuroimmunomodulation"},{"issue":"6","key":"2021120823555704100_B25","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/j.1399-3038.2011.01161.x","article-title":"Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test?","volume":"22","author":"Z\u00f6llner","year":"2011","journal-title":"Pediatr Allergy Immunol"},{"issue":"2","key":"2021120823555704100_B26","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1378\/chest.117.2.542","article-title":"Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique.","volume":"117","author":"Cochrane","year":"2000","journal-title":"Chest"},{"issue":"5","key":"2021120823555704100_B27","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1210\/jcem-48-5-861","article-title":"Direct inhibitory effect of dexamethasone on steroidogenesis of human adrenal in vivo.","volume":"48","author":"Saito","year":"1979","journal-title":"J Clin Endocrinol Metab"},{"issue":"4 pt 1","key":"2021120823555704100_B28","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1542\/peds.105.4.794","article-title":"Hypothalamic-pituitary-adrenal function and glucocorticoid sensitivity in atopic dermatitis.","volume":"105","author":"Ellison","year":"2000","journal-title":"Pediatrics"},{"issue":"5","key":"2021120823555704100_B29","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1136\/thx.2005.052456","article-title":"Oral and inhaled corticosteroids and adrenal insufficiency: a case-control study.","volume":"61","author":"Mortimer","year":"2006","journal-title":"Thorax"},{"issue":"3","key":"2021120823555704100_B30","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1515\/JPEM.2002.15.3.307","article-title":"The relation between adrenal function and the severity of bronchial hyperresponsiveness in children as measured by the methacholine provocation test.","volume":"15","author":"Barr","year":"2002","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"7","key":"2021120823555704100_B31","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nrendo.2009.106","article-title":"Stress and disorders of the stress system.","volume":"5","author":"Chrousos","year":"2009","journal-title":"Nat Rev Endocrinol"},{"issue":"2","key":"2021120823555704100_B32","first-page":"390","article-title":"The combined corticotropin-releasing hormone\/lysine vasopressin test discloses a corticotroph phenotype.","volume":"79","author":"Bertagna","year":"1994","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/130\/6\/e1512\/898867\/peds_2012-1147.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/130\/6\/e1512\/898867\/peds_2012-1147.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T05:18:20Z","timestamp":1639027100000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/130\/6\/e1512\/30303\/Hypothalamic-Pituitary-Adrenal-Axis-Suppression-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,1]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2012,12,1]]},"published-print":{"date-parts":[[2012,12,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2012-1147","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,1]]}}}