{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:08:34Z","timestamp":1755216514225,"version":"3.43.0"},"reference-count":20,"publisher":"Walter de Gruyter GmbH","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2025-0143_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Growth hormone (GH) deficiency in children is characterized by impaired linear growth and reduced growth velocity, necessitating confirmation through two GH stimulation tests. At the time of diagnosis, approximately 4\u202f% of children with GH deficiency exhibit concomitant adrenocorticotropic hormone (ACTH) deficiency, a prevalence that increases to 12\u202f% over the course of follow-up. The insulin tolerance test is regarded as the gold standard for assessing both cortisol and GH secretion; however, its clinical application is constrained by potential risks and the requirement for close medical supervision. This study aims to evaluate the effect of the L-dopa stimulation test on cortisol secretion in pediatric patients with short stature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2025-0143_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This retrospective study included 138 children (65 females, 73 males) who underwent the L-dopa stimulation test for the assessment of GH deficiency at the Pediatric Endocrinology Clinic between January 2010 and December 2023. Serum cortisol concentrations were measured at the 90th and 120th min of the test. Patients with a peak cortisol response &lt;18\u202f\u03bcg\/dL subsequently underwent a low-dose (1\u202f\u03bcg) ACTH stimulation test to further evaluate adrenal function. Clinical, anthropometric, and biochemical data were extracted from medical records and subjected to statistical analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2025-0143_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The mean age of the study cohort was 9.34\u00a0\u00b1 3.79 years, with 65 (47.1\u202f%) female and 73 (52.9\u202f%) male patients. The mean height standard deviation score (SDS) was\u00a0\u22122.62\u00a0\u00b1 0.83, while the mean weight SDS was\u00a0\u22121.81\u00a0\u00b1 1.09. The mean peak GH response was 5.64\u00a0\u00b1 4.0\u202fng\/mL following the clonidine stimulation test and 7.29\u00a0\u00b1 5.23\u202fng\/mL following the L-dopa test. A total of 35 children exhibited a peak cortisol response &lt;18\u202f\u03bcg\/dL during the L-dopa test. Among these, 35 underwent a low-dose (1\u202f\u03bcg) ACTH stimulation test, and 7 patients (20\u202f% of those tested; 5.1\u202f% of the total cohort) were diagnosed with adrenal insufficiency, defined as a peak cortisol response &lt;18\u202f\u03bcg\/dL. These patients were initiated on oral hydrocortisone therapy. Comparative analyses between patients with normal vs. impaired ACTH test responses (&lt;18\u202f\u03bcg\/dL vs.\u00a0\u226518\u202f\u03bcg\/dL) revealed no statistically significant differences in peak cortisol response to the L-dopa test, peak GH response to clonidine or L-dopa, age at presentation, gender, weight SDS, or height\u00a0SDS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2025-0143_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The L-dopa stimulation test may represent a valuable adjunctive tool for the evaluation of cortisol sufficiency in children undergoing assessment for suspected GH deficiency. However, further prospective studies with larger sample sizes and standardized protocols are warranted to validate its diagnostic accuracy and clinical utility in detecting adrenal insufficiency.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2025-0143","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T11:08:08Z","timestamp":1748603288000},"page":"824-829","source":"Crossref","is-referenced-by-count":0,"title":["Is L-dopa test effective in detecting adrenal insufficiency with preliminary diagnosis of growth hormone deficiency in children with short stature?"],"prefix":"10.1515","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-1251","authenticated-orcid":false,"given":"G\u00fcl\u00fcmay","family":"Vural Topakta\u015f","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Clinic , Izmir City Hospital , Izmir , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4770-0365","authenticated-orcid":false,"given":"Eren","family":"Er","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Clinic , Izmir City Hospital , Izmir , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sevim","family":"Onguner","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Clinic , Izmir City Hospital , Izmir , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benay","family":"Turan","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Clinic , Izmir City Hospital , Izmir , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bumin Nuri","family":"D\u00fcndar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pediatric Endocrinology , Izmir Katip Celebi University , Izmir , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"2025080412565944685_j_jpem-2025-0143_ref_001","doi-asserted-by":"crossref","unstructured":"Papadimitriou, A, Douros, K, Papadimitriou, DT, Kleanthous, K, Karapanou, O, Fretzayas, A. Characteristics of the short children referred to an academic paediatric endocrine clinic in Greece. J\u00a0Paediatr Child Health 2012;48:263\u20137. https:\/\/doi.org\/10.1111\/j.1440-1754.2011.02256.x.","DOI":"10.1111\/j.1440-1754.2011.02256.x"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_002","doi-asserted-by":"crossref","unstructured":"Galloway, P, McNeill, E, Paterson, W, Donaldson, M. Safety of the insulin tolerance test. Arch Dis Child 2002;87:354\u20136. https:\/\/doi.org\/10.1136\/adc.87.4.354.","DOI":"10.1136\/adc.87.4.354"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_003","doi-asserted-by":"crossref","unstructured":"Shah, A, Stanhope, R, Matthew, D. Hazards of pharmacological tests of growth hormone secretion in childhood. BMJ Br Med J 1992;304:173. https:\/\/doi.org\/10.1136\/bmj.304.6820.173.","DOI":"10.1136\/bmj.304.6820.173"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_004","doi-asserted-by":"crossref","unstructured":"King, AB. The effect of exogenous dopamine on ACTH secretion. Proc Soc Exp Biol Med 1969;130:445\u20137. https:\/\/doi.org\/10.3181\/00379727-130-33575.","DOI":"10.3181\/00379727-130-33575"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_005","doi-asserted-by":"crossref","unstructured":"Nilsson, K, Thorell, J. The effect of l\u2010dopa on the blood concentrations of growth hormone, thyrotrophin, gonadotrophins, cortisol and glucose in children with short stature. Acta P\u00e6diatr 1974;63:812\u20136. https:\/\/doi.org\/10.1111\/j.1651-2227.1974.tb04869.x.","DOI":"10.1111\/j.1651-2227.1974.tb04869.x"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_006","doi-asserted-by":"crossref","unstructured":"Hayek, A, Crawford, JD. L-DOPA and pituitary hormone secretion. J\u00a0Clin Endocrinol Metab 1972;34:764\u20136. https:\/\/doi.org\/10.1210\/jcem-34-5-764.","DOI":"10.1210\/jcem-34-5-764"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_007","doi-asserted-by":"crossref","unstructured":"Vizner, B, Reiner, \u017d, Sekso, M. Effect of L-dopa on growth hormone, glucose, insulin, and cortisol response in obese subjects. Exp Clin Endocrinol Diabetes 1983;81:41\u20138. https:\/\/doi.org\/10.1055\/s-0029-1210205.","DOI":"10.1055\/s-0029-1210205"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_008","doi-asserted-by":"crossref","unstructured":"Chambers, J, Brown, G. Neurotransmitter regulation of growth hormone and ACTH in the rhesus monkey: effects of biogenic amines. Endocrinology 1976;98:420\u20138. https:\/\/doi.org\/10.1210\/endo-98-2-420.","DOI":"10.1210\/endo-98-2-420"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_009","doi-asserted-by":"crossref","unstructured":"Pivonello, R, Ferone, D, Lombardi, G, Colao, A, Lamberts, SW, Hofland, LJ. Novel insights in dopamine receptor physiology. Eur J Endocrinol 2007;156:S13\u201321. https:\/\/doi.org\/10.1530\/eje.1.02353.","DOI":"10.1530\/eje.1.02353"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_010","doi-asserted-by":"crossref","unstructured":"Jaffe, CA, DeMott-Friberg, R, Barkan, AL. Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli. J\u00a0Clin Investig 1996;97:934\u201340. https:\/\/doi.org\/10.1172\/jci118516.","DOI":"10.1172\/JCI118516"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_011","doi-asserted-by":"crossref","unstructured":"BoydIIIA, Lebovitz, HE, Pfeiffer, JB. Stimulation of human-growth-hormone secretion by L-dopa. N\u00a0Engl J Med 1970;283:1425\u20139. https:\/\/doi.org\/10.1056\/nejm197012242832602.","DOI":"10.1056\/NEJM197012242832602"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_012","doi-asserted-by":"crossref","unstructured":"Buonocore, F, McGlacken-Byrne, SM, Del Valle, I, Achermann, JC. Current insights into adrenal insufficiency in the newborn and young infant. Front Pediatr 2020;8:619041. https:\/\/doi.org\/10.3389\/fped.2020.619041.","DOI":"10.3389\/fped.2020.619041"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_013","doi-asserted-by":"crossref","unstructured":"Rogol, AD, Hayden, GF. Etiologies and early diagnosis of short stature and growth failure in children and adolescents. J\u00a0Pediatr 2014;164:S1\u20134. https:\/\/doi.org\/10.1016\/j.jpeds.2014.02.027.","DOI":"10.1016\/j.jpeds.2014.02.027"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_014","doi-asserted-by":"crossref","unstructured":"Lim, SH, Vasanwala, R, Lek, N, Yap, F. Quantifying the risk of hypoglycaemia in children undergoing the glucagon stimulation test. Clin EndocrinolEndocrinol 2011;75:489\u201394. https:\/\/doi.org\/10.1111\/j.1365-2265.2011.04117.x.","DOI":"10.1111\/j.1365-2265.2011.04117.x"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_015","doi-asserted-by":"crossref","unstructured":"Demir, K, \u00d6zen, S, Konak\u00e7\u0131, E, Ayd\u0131n, M, Darendeliler, F. A comprehensive online calculator for pediatric endocrinologists: \u00c7EDD \u00c7\u00f6z\u00fcm\/TPEDS metrics. J\u00a0Clin Res Pediat Endocrinol 2017;9:182. https:\/\/doi.org\/10.4274\/jcrpe.4526.","DOI":"10.4274\/jcrpe.4526"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_016","doi-asserted-by":"crossref","unstructured":"Marakaki, C, Papadimitriou, DT, Kleanthous, K, Papadopoulou, A, Papadimitriou, A. L-dopa stimulates cortisol secretion through adrenocorticotropic hormone release in short children. Hormone Res Paediatr 2015;84:319\u201322. https:\/\/doi.org\/10.1159\/000439532.","DOI":"10.1159\/000439532"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_017","doi-asserted-by":"crossref","unstructured":"Marakaki, C, Papadimitriou, D, Papadopoulou, A, Fretzayas, A, Papadimitriou, A. L-dopa is a potent stimulator of cortisol in short children. Hormone Res Paediatr 2014;81:386\u201390. https:\/\/doi.org\/10.1159\/000357268.","DOI":"10.1159\/000357268"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_018","doi-asserted-by":"crossref","unstructured":"Acar, S, Paket\u00e7i, A, Tuhan, H, Demir, K, B\u00f6ber, E, Abaci, A. Comparison of the effects of the L-dopa and insulin tolerance tests on cortisol secretion. J\u00a0Endocrinol Investig 2018;41:901\u20137. https:\/\/doi.org\/10.1007\/s40618-017-0815-7.","DOI":"10.1007\/s40618-017-0815-7"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_019","doi-asserted-by":"crossref","unstructured":"K\u0131rkg\u00f6z, T, Acar, S, Nalbanto\u011flu, \u00d6, \u00d6zkan, B. Results confirming the efficacy of oral L-dopa on cortisol secretion in patients being evaluated for suspected growth hormone deficiency. Trends Pediatr 2023;4:19\u201323. https:\/\/doi.org\/10.59213\/tp.2023.40316.","DOI":"10.59213\/TP.2023.40316"},{"key":"2025080412565944685_j_jpem-2025-0143_ref_020","doi-asserted-by":"crossref","unstructured":"Stratakis, CA, Rusovici, DE, Kulin, HE, Finkelstein, JW. Dysregulation of the hypothalamic-pituitary-adrenal axis in short children with and without growth hormone deficiency. J\u00a0Pediatr Endocrinol Metabol 2000;13:1095\u2013100. https:\/\/doi.org\/10.1515\/jpem.2000.13.8.1095.","DOI":"10.1515\/JPEM.2000.13.8.1095"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2025-0143\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2025-0143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T12:57:16Z","timestamp":1754312236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2025-0143\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":20,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,5]]},"published-print":{"date-parts":[[2025,8,26]]}},"alternative-id":["10.1515\/jpem-2025-0143"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2025-0143","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"type":"print","value":"0334-018X"},{"type":"electronic","value":"2191-0251"}],"subject":[],"published":{"date-parts":[[2025,5,29]]}}}