{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:51:36Z","timestamp":1776851496910,"version":"3.51.2"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>To investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), \u03944-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0\u201325.1) ng\/mL; T1: 7.1 (1.8\u201319.9) ng\/mL; T2: 5.9 (2.0\u201320.0) ng\/mL, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005], and \u03944-androstenedione [T0: 0.9 (0.3\u20132.5) ng\/mL; T1: 0.3 (0.3\u20131.1) ng\/mL; T2: 0.5 (0.3\u20131.5) ng\/mL, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and \u03944-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations\/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, \u03944-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>our data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12020-024-03792-6","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T10:25:12Z","timestamp":1711535112000},"page":"727-734","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Increased risk of nephrolithiasis: an emerging issue in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency"],"prefix":"10.1007","volume":"84","author":[{"given":"Mariangela","family":"Chiarito","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crescenza","family":"Lattanzio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vito","family":"D\u2019Ascanio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Capalbo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Cavarzere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Grandone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Aiello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Pepe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Wasniewska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Zoller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariacarolina","family":"Salerno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Felicia","family":"Faienza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"3792_CR1","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1016\/S0140-6736(17)31431-9","volume":"390","author":"D El-Maouche","year":"2017","unstructured":"D. El-Maouche, W. Arlt, D.P. Merke, Congenital adrenal hyperplasia. Lancet 390, 2194\u20132210 (2017). https:\/\/doi.org\/10.1016\/S0140-6736(17)31431-9","journal-title":"Lancet"},{"key":"3792_CR2","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.jpag.2017.04.001","volume":"30","author":"SF Witchel","year":"2017","unstructured":"S.F. Witchel, Congenital adrenal hyperplasia. J. Pediatr. Adolesc. Gynecol. 30, 520\u2013534 (2017). https:\/\/doi.org\/10.1016\/j.jpag.2017.04.001","journal-title":"J. Pediatr. Adolesc. Gynecol."},{"key":"3792_CR3","doi-asserted-by":"publisher","first-page":"4043","DOI":"10.1210\/jc.2018-01865","volume":"103","author":"PW Speiser","year":"2018","unstructured":"P.W. Speiser, W. Arlt, R.J. Auchus, L.S. Baskin, G.S. Conway, D.P. Merke et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 103, 4043\u20134088 (2018). https:\/\/doi.org\/10.1210\/jc.2018-01865","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"3792_CR4","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1159\/000509548","volume":"93","author":"MG Wasniewska","year":"2020","unstructured":"M.G. Wasniewska, L.A. Morabito, F. Baronio, S. Einaudi, M. Salerno, C. Bizzarri et al. Growth trajectory and adult height in children with nonclassical congenital adrenal hyperplasia. Horm. Res. Paediatr. 93, 173\u2013181 (2020). https:\/\/doi.org\/10.1159\/000509548","journal-title":"Horm. Res. Paediatr."},{"key":"3792_CR5","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1055\/a-0820-2085","volume":"127","author":"N Reisch","year":"2019","unstructured":"N. Reisch, Review of health problems in adult patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Exp. Clin. Endocrinol. Diabetes 127, 171\u2013177 (2019). https:\/\/doi.org\/10.1055\/a-0820-2085","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"3792_CR6","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3803\/EnM.2022.1528","volume":"37","author":"A Nordenstr\u00f6m","year":"2022","unstructured":"A. Nordenstr\u00f6m, S. Lajic, H. Falhammar, Long-term outcomes of congenital adrenal hyperplasia. Endocrinol. Metab. 37, 587\u2013598 (2022). https:\/\/doi.org\/10.3803\/EnM.2022.1528","journal-title":"Endocrinol. Metab."},{"key":"3792_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/250462","volume":"2013","author":"A Ventura","year":"2013","unstructured":"A. Ventura, G. Brunetti, S. Colucci, A. Oranger, F. Ladisa, L. Cavallo et al. Glucocorticoid-induced osteoporosis in children with 21-hydroxylase deficiency. Bio. Med. Res. Int. 2013, 1\u20138 (2013). https:\/\/doi.org\/10.1155\/2013\/250462","journal-title":"Bio. Med. Res. Int."},{"key":"3792_CR8","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1007\/s12020-014-0332-9","volume":"48","author":"M Delvecchio","year":"2015","unstructured":"M. Delvecchio, L. Soldano, A. Lonero, A. Ventura, P. Giordano, L. Cavallo et al. Evaluation of impact of steroid replacement treatment on bone health in children with 21-hydroxylase deficiency. Endocrine 48, 995\u20131000 (2015). https:\/\/doi.org\/10.1007\/s12020-014-0332-9","journal-title":"Endocrine"},{"key":"3792_CR9","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/s41574-022-00655-w","volume":"18","author":"A Mallappa","year":"2022","unstructured":"A. Mallappa, D.P. Merke, Management challenges and therapeutic advances in congenital adrenal hyperplasia. Nat. Rev. Endocrinol. 18, 337\u2013352 (2022). https:\/\/doi.org\/10.1038\/s41574-022-00655-w","journal-title":"Nat. Rev. Endocrinol."},{"key":"3792_CR10","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.juro.2012.03.021","volume":"188","author":"ME Dwyer","year":"2012","unstructured":"M.E. Dwyer, A.E. Krambeck, E.J. Bergstralh, D.S. Milliner, J.C. Lieske, A.D. Rule, Temporal trends in incidence of kidney stones among children: A 25-year population based study. J. Urol. 188, 247\u2013252 (2012). https:\/\/doi.org\/10.1016\/j.juro.2012.03.021","journal-title":"J. Urol."},{"key":"3792_CR11","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1111\/ped.12186","volume":"55","author":"I Bilge","year":"2013","unstructured":"I. Bilge, A. Yilmaz, S.M. Kayiran, S. Emre, A. Kadioglu, E. Yekeler et al. Clinical importance of renal calyceal microlithiasis in children. Pediatr. Int. 55, 731\u2013736 (2013). https:\/\/doi.org\/10.1111\/ped.12186","journal-title":"Pediatr. Int."},{"key":"3792_CR12","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1007\/s00467-009-1231-9","volume":"24","author":"H Alpay","year":"2009","unstructured":"H. Alpay, A. Ozen, I. Gokce, N. Biyikli, Clinical and metabolic features of urolithiasis and microlithiasis in children. Pediatr. Nephrol. 24, 2203\u20132209 (2009). https:\/\/doi.org\/10.1007\/s00467-009-1231-9","journal-title":"Pediatr. Nephrol."},{"key":"3792_CR13","doi-asserted-by":"publisher","first-page":"70","DOI":"10.15171\/jrip.2017.13","volume":"6","author":"MA Fallahzadeh","year":"2016","unstructured":"M.A. Fallahzadeh, J. Hassanzadeh, M.H. Fallahzadeh, What do we know about pediatric renal microlithiasis? J. Ren. Inj. Prev. 6, 70\u201375 (2016). https:\/\/doi.org\/10.15171\/jrip.2017.13","journal-title":"J. Ren. Inj. Prev."},{"key":"3792_CR14","doi-asserted-by":"publisher","first-page":"552","DOI":"10.3390\/healthcare11040552","volume":"11","author":"B Cao","year":"2023","unstructured":"B. Cao, R. Daniel, R. McGregor, G.E. Tasian, Pediatric. Nephrolithiasis. Healthcare 11, 552 (2023). https:\/\/doi.org\/10.3390\/healthcare11040552","journal-title":"Healthcare"},{"key":"3792_CR15","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3389\/fped.2018.00098","volume":"6","author":"A Weigert","year":"2018","unstructured":"A. Weigert, B. Hoppe, Nephrolithiasis and nephrocalcinosis in childhood-risk factor-related current and future treatment options. Front. Pediatr. 6, 98 (2018). https:\/\/doi.org\/10.3389\/fped.2018.00098","journal-title":"Front. Pediatr."},{"key":"3792_CR16","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1210\/js.2017-00145","volume":"1","author":"MJ Schoelwer","year":"2017","unstructured":"M.J. Schoelwer, V. Viswanathan, A. Wilson, C. Nailescu, E.A. Imel, Infants with congenital adrenal hyperplasia are at risk for hypercalcemia, hypercalciuria, and nephrocalcinosis. J. Endocr. Soc. 1, 1160\u20131167 (2017). https:\/\/doi.org\/10.1210\/js.2017-00145","journal-title":"J. Endocr. Soc."},{"key":"3792_CR17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.4103\/jrms.jrms_872_21","volume":"27","author":"Y Madihi","year":"2022","unstructured":"Y. Madihi, N. Mostofizadeh, H. Shamsipour Dehkordi, M. Riahinezhad, S. Hovsepian, N. Rostampour et al. Prevalence of nephrocalcinosis in children with congenital adrenal hyperplasia. J. Res. Med. Sci. 27, 16 (2022). https:\/\/doi.org\/10.4103\/jrms.jrms_872_21","journal-title":"J. Res. Med. Sci."},{"key":"3792_CR18","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/BF03344156","volume":"29","author":"E Cacciari","year":"2006","unstructured":"E. Cacciari, S. Milani, A. Balsamo, E. Spada, G. Bona, L. Cavallo et al. Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J. Endocrinol. Invest. 29, 581\u2013593 (2006). https:\/\/doi.org\/10.1007\/BF03344156","journal-title":"J. Endocrinol. Invest."},{"key":"3792_CR19","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1136\/adc.51.3.170","volume":"51","author":"JM Tanner","year":"1976","unstructured":"J.M. Tanner, R.H. Whitehouse, Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch. Dis. Child. 51, 170\u2013179 (1976). https:\/\/doi.org\/10.1136\/adc.51.3.170","journal-title":"Arch. Dis. Child."},{"key":"3792_CR20","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1007\/s00345-005-0033-3","volume":"23","author":"A Hesse","year":"2005","unstructured":"A. Hesse, Reliable data from diverse regions of the world exist to show that there has been a steady increase in the prevalence of urolithiasis. World J. Urol. 23, 302\u2013303 (2005). https:\/\/doi.org\/10.1007\/s00345-005-0033-3","journal-title":"World J. Urol."},{"key":"3792_CR21","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.jpeds.2010.02.004","volume":"157","author":"DJ Sas","year":"2010","unstructured":"D.J. Sas, T.C. Hulsey, I.F. Shatat, J.K. Orak, Increasing incidence of kidney stones in children evaluated in the emergency department. J. Pediatr. 157, 132\u2013137 (2010). https:\/\/doi.org\/10.1016\/j.jpeds.2010.02.004","journal-title":"J. Pediatr."},{"key":"3792_CR22","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1007\/s11255-009-9623-0","volume":"42","author":"FR Spivacow","year":"2010","unstructured":"F.R. Spivacow, A.L. Negri, E.E. Del Valle, I. Calvi\u00f1o, J.R. Zanchetta, Clinical and metabolic risk factor evaluation in young adults with kidney stones. Int. Urol. Nephrol. 42, 471\u2013475 (2010). https:\/\/doi.org\/10.1007\/s11255-009-9623-0","journal-title":"Int. Urol. Nephrol."},{"key":"3792_CR23","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1159\/000455698","volume":"135","author":"CP Kovesdy","year":"2017","unstructured":"C.P. Kovesdy, S.L. Furth, C. Zoccali; on behalf of the World Kidney Day Steering Committee, Obesity and kidney disease: Hidden consequences of the epidemic. Nephron 135, 243\u2013251 (2017). https:\/\/doi.org\/10.1159\/000455698","journal-title":"Nephron"},{"key":"3792_CR24","doi-asserted-by":"publisher","first-page":"379","DOI":"10.12659\/PJR.894678","volume":"80","author":"P Hira","year":"2015","unstructured":"P. Hira, Renal cysts and nephrocalcinosis in a patient deficient in 11 beta-hydroxylase enzyme. Pol. J. Radiol. 80, 379\u2013381 (2015). https:\/\/doi.org\/10.12659\/PJR.894678","journal-title":"Pol. J. Radiol."},{"key":"3792_CR25","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1007\/s00467-004-1732-5","volume":"20","author":"T Watanabe","year":"2005","unstructured":"T. Watanabe, T. Tajima, Renal cysts and nephrocalcinosis in a patient with Bartter syndrome type III. Pediatr. Nephrol. 20, 676\u2013678 (2005). https:\/\/doi.org\/10.1007\/s00467-004-1732-5","journal-title":"Pediatr. Nephrol."}],"container-title":["Endocrine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-024-03792-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12020-024-03792-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-024-03792-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T06:25:11Z","timestamp":1715063111000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12020-024-03792-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["3792"],"URL":"https:\/\/doi.org\/10.1007\/s12020-024-03792-6","relation":{},"ISSN":["1559-0100"],"issn-type":[{"value":"1559-0100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,27]]},"assertion":[{"value":"30 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study involved human participants, their data and biological material. Approval was obtained from the ethics committee of Policlinico of Bari, Italy. The procedures used in this study adhere to the tenets of the 1964 Declaration of Helsinki and its later amendments.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all parents of individual participants included in the study. An oral assent was obtained by the patients themselves.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors affirm that human research participants provided informed consent for publication of all the clinical and molecular data inhere presented in the document.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}