{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:43:32Z","timestamp":1792640612243,"version":"4.5.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009433","name":"Istituto Auxologico Italiano","doi-asserted-by":"publisher","award":["05C622_2016"],"award-info":[{"award-number":["05C622_2016"]}],"id":[{"id":"10.13039\/501100009433","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006692","name":"Universit\u00e0 degli Studi di Torino","doi-asserted-by":"publisher","award":["ex-60% 2020"],"award-info":[{"award-number":["ex-60% 2020"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009448","name":"Universit\u00e0 degli Studi della Campania Luigi Vanvitelli","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009448","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Endocrinol Invest"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify.\u00a0<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>We describe KS clinical presentation in a large Italian cohort.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Design<\/jats:title>\n                <jats:p>This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Mean age at diagnosis was 37.4\u2009\u00b1\u200913.4\u00a0years. The overall mean testicular size was 3\u00a0ml, and 2.5\u00a0ml in both testes in untreated KS group. BMI was 26.6\u2009\u00b1\u20095.8\u00a0kg\/m<jats:sup>2<\/jats:sup>, and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350\u2009\u00b1\u20099.1\u00a0ng\/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early\u00a0detection\u00a0and\u00a0timely\u00a0treatment are mandatory.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s40618-022-01816-4","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T10:02:54Z","timestamp":1653386574000},"page":"1769-1776","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-635X","authenticated-orcid":false,"given":"D.","family":"Pasquali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Chiodini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Simeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ferlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Vignozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Corona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Lanfranco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Rochira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. E.","family":"Calogero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bonomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Pivonello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Balercia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pizzocaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. A.","family":"Giagulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Salacone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Aversa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Accardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Isidori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Foresta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. A.","family":"Jannini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Garolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the KING, Klinefelter ItaliaN Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Pasquali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ferlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Vignozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Corona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Lanfranco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Rochira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. E.","family":"Calogero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bonomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Pivonello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Balercia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pizzocaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. A.","family":"Giagulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Salacone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Aversa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Accardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Isidori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Foresta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. A.","family":"Jannini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Garolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"issue":"11","key":"1816_CR1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1210\/jcem-2-11-615","volume":"2","author":"HF Klinefelter","year":"1942","unstructured":"Klinefelter HF, Reifenstein EC, Albright F (1942) Syndrome characterized by gynecomastia, aspermatogenesis without A-Leydigism, and increased excretion of follicle stimulating hormone. J Clin Endocrinol Metab 2(11):615\u2013627","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"1816_CR2","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1111\/andr.12208","volume":"4","author":"E Nieschlag","year":"2016","unstructured":"Nieschlag E, Ferlin A, Gravholt CH, Gromoll J, K\u00f6hler B, Lejeune H, Rogol AD, Wistuba J (2016) The Klinefelter syndrome: current management and research challenges. Andrology 4(3):545\u2013549","journal-title":"Andrology"},{"issue":"1","key":"1816_CR3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1210\/jc.2012-2382","volume":"98","author":"KA Groth","year":"2013","unstructured":"Groth KA, Skakkeb\u00e6k A, H\u00f8st C, Gravholt CH, Bojesen A (2013) Clinical review: Klinefelter syndrome\u2013a clinical update. J Clin Endocrinol Metab 98(1):20\u201330","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"1816_CR4","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s40618-016-0541-6","volume":"40","author":"M Bonomi","year":"2017","unstructured":"Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A Klinefelter ItaliaN Group (KING) (2017) Klinefelter\u00a0syndrome\u00a0(KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Invest 40(2):123\u2013134","journal-title":"J Endocrinol Invest"},{"key":"1816_CR5","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1111\/andr.12636","volume":"7","author":"GA Kanakis","year":"2019","unstructured":"Kanakis GA, Nordkap L, Bang AK, Calogero AE, B\u00e1rtfai G, Corona G, Forti G, Toppari J, Goulis DG, J\u00f8rgensen N (2019) EAA clinical practice guidelines\u2014gynecomastia evaluation and management. Andrology 7:778\u2013793","journal-title":"Andrology"},{"issue":"2","key":"1816_CR6","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2174\/1871530318666180703160250","volume":"19","author":"VA Giagulli","year":"2019","unstructured":"Giagulli VA, Campone B, Castellana M, Salzano C, Fisher AD, de Angelis C, Pivonello R, Colao A, Pasquali D, Maggi M, Triggiani V, On Behalf Of The Klinefelter ItaliaN Group KING (2019) Neuropsychiatric aspects in men with\u00a0Klinefelter\u00a0syndrome. Endocr Metab Immune Disord Drug Targets 19(2):109\u2013115","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"1816_CR7","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13023-018-0976-2","volume":"14","author":"A Berglund","year":"2019","unstructured":"Berglund A, Viuff MH, Skakkeb\u00e6k A, Chang S, Stochholm K, Gravholt CH (2019) Changes in the cohort composition of Turner syndrome and severe non-diagnosis of Klinefelter, 47, XXX and 47, XYY syndrome: a nationwide cohort study. Orphanet J Rare Dis 14:16. https:\/\/doi.org\/10.1186\/s13023-018-0976-2","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"1816_CR8","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1093\/humupd\/dmx008","volume":"23","author":"Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, Ferlin A, Foresta C, Jannini EA, Maggi M, Lenzi A, Pasquali D, Francavilla S; Klinefelter ItaliaN Group (KING)","year":"2017","unstructured":"Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, Ferlin A, Foresta C, Jannini EA, Maggi M, Lenzi A, Pasquali D, Francavilla S; Klinefelter ItaliaN Group (KING) (2017) Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis. Hum Reprod Update 23(3):265\u2013275","journal-title":"Hum Reprod Update"},{"issue":"2","key":"1816_CR9","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1007\/s12020-018-1584-1586","volume":"61","author":"A Salzano","year":"2018","unstructured":"Salzano A, D\u2019Assante R, Heaney LM, Monaco F, Rengo G, Valente P, Pasquali D, Bossone E, Gianfrilli D, Lenzi A, Cittadini A, Marra AM, Napoli R (2018) Klinefelter syndrome, insulin resistance, metabolic\u00a0syndrome, and diabetes:\u00a0review\u00a0of literature and clinical perspectives. Endocrine 61(2):194\u2013203. https:\/\/doi.org\/10.1007\/s12020-018-1584-1586","journal-title":"Endocrine"},{"issue":"7","key":"1816_CR10","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1007\/s40618-017-0619-9","volume":"40","author":"AE Calogero","year":"2017","unstructured":"Calogero AE, Giagulli VA, Mongio\u00ec LM, Triggiani V, Radicioni AF, Jannini EA, Pasquali D, Klinefelter ItaliaN Group (KING) (2017) Klinefelter\u00a0syndrome: cardiovascular abnormalities and metabolic disorders. J Endocrinol Invest 40(7):705\u2013712","journal-title":"J Endocrinol Invest"},{"key":"1816_CR11","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1007\/s40618-019-01037-2","volume":"42","author":"G Balercia","year":"2019","unstructured":"Balercia G, Bonomi M, Giagulli VA, Lanfranco F, Rochira V, Giambersio A, Accardo G, Esposito D, Allasia S, Cangiano B, De Vincentis S, Condorelli RA, Calogero A, Pasquali D, KING group (2019) Thyroid function in Klinefelter syndrome: a multicentre study from KING group. J Endocrinol Invest 42:1199\u20131204","journal-title":"J Endocrinol Invest"},{"issue":"1","key":"1816_CR12","doi-asserted-by":"publisher","first-page":"154","DOI":"10.4103\/1008-682X.128514","volume":"17","author":"G Accardo","year":"2015","unstructured":"Accardo G, Vallone G, Esposito D, Barbato F, Renzullo A, Conzo G, Docimo G, Esposito K, Pasquali D (2015) Testicular parenchymal abnormalities in Klinefelter syndrome: a question of cancer? Examination of 40 consecutive patients. Asian J Androl 17(1):154\u2013158","journal-title":"Asian J Androl"},{"issue":"2","key":"1816_CR13","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/j.ijcard.2012.09.215","volume":"168","author":"D Pasquali","year":"2013","unstructured":"Pasquali D, Arcopinto M, Renzullo A, Rotondi M, Accardo G, Salzano A, Esposito D, Saldamarco L, Isidori AM, Marra AM, Ruvolo A, Napoli R, Bossone E, Lenzi A, Baliga RR, Sacc\u00e0 L, Cittadini A (2013) Cardiovascular abnormalities in Klinefelter syndrome. Int J Cardiol 168(2):754\u2013759","journal-title":"Int J Cardiol"},{"issue":"5","key":"1816_CR14","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1111\/andr.12080","volume":"3","author":"MN Di Minno","year":"2015","unstructured":"Di Minno MN, Esposito D, Di Minno A, Accardo G, Lupoli G, Cittadini A, Giugliano D, Pasquali D (2015) Increased platelet reactivity in Klinefelter men: something new to consider. Andrology 3(5):876\u2013881","journal-title":"Andrology"},{"issue":"4","key":"1816_CR15","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1210\/clinem\/dgaa936","volume":"106","author":"I Rita","year":"2021","unstructured":"Rita I, Ferrante E, Scalambrino E, Profka E, Clerici M, Lettera T, Serban AL, Vena W, Pizzocaro A, Bonomi M, Cangiano B, Carosi G, Mazziotti G, Persani L, Lania A, Arosio M, Peyvandi F, Mantovani G, Tripodi A (2021) Procoagulant imbalance in Klinefelter syndrome assessed by thrombin generation assay and whole blood thromboelastometry. J Clin Endocrinol Metab 106(4):1660\u20131672","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"1816_CR16","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/cen.12245","volume":"80","author":"M Rotondi","year":"2014","unstructured":"Rotondi M, Coperchini F, Renzullo A, Accardo G, Esposito D, Groppelli G, Magri F, Cittadini A, Isidori AM, Chiovato L, Pasquali D (2014) High circulating levels of CCL2 in patients with Klinefelter\u2019s syndrome. Clin Endocrinol (Oxf) 80(3):465\u2013467","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"1816_CR17","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1210\/er.2017-00212","volume":"39","author":"CH Gravholt","year":"2018","unstructured":"Gravholt CH, Chang S, Wallentin M, Fedder J, Moore P, Klinefelter SA (2018) Syndrome: integrating genetics, neuropsychology, and endocrinology. Endocr Rev 39(4):389\u2013423","journal-title":"Endocr Rev"},{"issue":"12","key":"1816_CR18","doi-asserted-by":"publisher","first-page":"6516","DOI":"10.1210\/jc.2005-1077","volume":"90","author":"AJ Swerdlow","year":"2005","unstructured":"Swerdlow AJ, Higgins CD, Schoemaker MJ, Wright AF, Jacobs PA, United Kingdom Clinical Cytogenetics Group (2005) Mortality in patients with Klinefelter syndrome in Britain a cohort study. J Clin Endocrinol Metab 90(12):6516\u20136522","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1816_CR19","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1210\/jc.2005-0697","volume":"91","author":"A Bojesen","year":"2006","unstructured":"Bojesen A, Juul S, Birkebaek NH, Gravholt CH (2006) Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J Clin Endocrinol Metab 91(4):1254\u20131260. https:\/\/doi.org\/10.1210\/jc.2005-0697","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"1816_CR20","doi-asserted-by":"publisher","first-page":"3666","DOI":"10.1210\/jcem.84.10.6079","volume":"84","author":"A Vermeulen","year":"1999","unstructured":"Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84(10):3666\u20133672","journal-title":"J Clin Endocrinol Metab"},{"issue":"19","key":"1816_CR21","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1001\/jama.285.19.2486","volume":"285","author":"Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults","year":"2001","unstructured":"Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults  (2001) Executive Summary of the third Report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285(19):2486\u20132497. https:\/\/doi.org\/10.1001\/jama.285.19.2486","journal-title":"JAMA"},{"issue":"4","key":"1816_CR22","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/j.1365-2265.1975.tb01547.x","volume":"4","author":"C Wang","year":"1975","unstructured":"Wang C, Baker HW, Burger HG, De Kretser DM, Hudson B (1975) Hormonal studies in Klinefelter\u2019s syndrome. Clin Endocrinol (Oxf) 4(4):399\u2013411","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"9430","key":"1816_CR23","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S0140-6736(04)16678-6","volume":"364","author":"F Lanfranco","year":"2004","unstructured":"Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E (2004) Klinefelter\u2019s syndrome. Lancet 364(9430):273\u2013283","journal-title":"Lancet"},{"issue":"7","key":"1816_CR24","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.2337\/dc06-0145","volume":"29","author":"A Bojesen","year":"2006","unstructured":"Bojesen A, Kristensen K, Birkebaek NH, Fedder J, Mosekilde L, Bennett P, Laurberg P, Frystyk J, Flyvbjerg A, Christiansen JS, Gravholt CH (2006) The metabolic syndrome is frequent in Klinefelter\u2019s syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care 29(7):1591\u20131598","journal-title":"Diabetes Care"},{"issue":"6","key":"1816_CR25","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1016\/j.urology.2008.01.051","volume":"71","author":"T Ishikawa","year":"2008","unstructured":"Ishikawa T, Yamaguchi K, Kondo Y, Takenaka A, Fujisawa M (2008) Metabolic syndrome in men with Klinefelter\u2019s syndrome. Urology 71(6):1109\u20131113","journal-title":"Urology"},{"issue":"9","key":"1816_CR26","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1530\/EC-19-0323","volume":"8","author":"C H\u00f8st","year":"2019","unstructured":"H\u00f8st C, Bojesen A, Erlandsen M, Groth KA, Kristensen K, Jurik AG, Birkeb\u00e6k NH, Gravholt CH (2019) A placebo-controlled randomized study with testosterone in Klinefelter syndrome: beneficial effects on body composition. Endocr Connect 8(9):1250\u20131261","journal-title":"Endocr Connect"},{"issue":"12","key":"1816_CR27","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1007\/s40618-020-01299-1","volume":"43","author":"A Pizzocaro","year":"2020","unstructured":"Pizzocaro A, Vena W, Condorelli R, Radicioni A, Rastrelli G, Pasquali D, Selice R, Ferlin A, Foresta C, Jannini EA, Maggi M, Lenzi A, Pivonello R, Isidori AM, Garolla A, Francavilla S, Corona G, KING, Klinefelter ItaliaN Group (2020) Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis. J Endocrinol Invest 43(12):1675\u20131687","journal-title":"J Endocrinol Invest"},{"issue":"5","key":"1816_CR28","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1210\/jc.2007-2177","volume":"93","author":"M Grossmann","year":"2008","unstructured":"Grossmann M, Thomas MC, Panagiotopoulos S, Sharpe K, MacIsaac RJ, Clarke S, Zajac JD, Jerums G (2008) Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab 93(5):1834\u20131840","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"1816_CR29","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1097\/MED.0b013e32833919cf","volume":"17","author":"M Grossmann","year":"2010","unstructured":"Grossmann M, Gianatti EJ, Zajac JD (2010) Testosterone and type 2 diabetes. Curr Opin Endocrinol Diabetes Obes 17(3):247\u2013256","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"issue":"2","key":"1816_CR30","doi-asserted-by":"publisher","first-page":"234","DOI":"10.2337\/dc06-1579","volume":"30","author":"E Selvin","year":"2007","unstructured":"Selvin E, Feinleib M, Zhang L, Rohrmann S, Rifai N, Nelson WG, Dobs A, Basaria S, Golden SH, Platz EA (2007) Androgens and diabetes in men: results from the third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care 30(2):234\u2013238","journal-title":"Diabetes Care"},{"key":"1816_CR31","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.maturitas.2019.04.203","volume":"125","author":"GA Kanakis","year":"2019","unstructured":"Kanakis GA, Tsametis CP, Goulis DG (2019) Measuring testosterone in women and men. Maturitas 125:41\u201344","journal-title":"Maturitas"},{"issue":"3","key":"1816_CR32","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1210\/jc.2014-2780","volume":"100","author":"M Zitzmann","year":"2015","unstructured":"Zitzmann M, Bongers R, Werler S, Bogdanova N, Wistuba J, Kliesch S, Gromoll J, T\u00fcttelmann F (2015) Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome. J Clin Endocrinol Metab 100(3):518\u2013523","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1816_CR33","doi-asserted-by":"publisher","first-page":"726","DOI":"10.2164\/jandrol.108.007005","volume":"30","author":"AE Heufelder","year":"2009","unstructured":"Heufelder AE, Saad F, Bunck MC, Gooren L (2009) Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl 30(6):726\u2013733","journal-title":"J Androl"},{"issue":"1","key":"1816_CR34","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.1038\/sj.ejcn.1600980","volume":"54","author":"G Samuelson","year":"2000","unstructured":"Samuelson G (2000) Dietary habits and nutritional status in adolescents over Europe. An overview of current studies in the Nordic countries. Eur J Clin Nutr 54(1):S21\u2013S28. https:\/\/doi.org\/10.1038\/sj.ejcn.1600980","journal-title":"Eur J Clin Nutr"},{"issue":"1","key":"1816_CR35","doi-asserted-by":"publisher","first-page":"S29","DOI":"10.1038\/sj.ejcn.1600981","volume":"54","author":"JA Cruz","year":"2000","unstructured":"Cruz JA (2000) Dietary habits and nutritional status in adolescents over Europe-Southern Europe. Eur J Clin Nutr 54(1):S29-35","journal-title":"Eur J Clin Nutr"},{"issue":"1","key":"1816_CR36","doi-asserted-by":"publisher","first-page":"24","DOI":"10.5694\/j.1326-5377.2011.tb04141.x","volume":"194","author":"AS Herlihy","year":"2011","unstructured":"Herlihy AS, Halliday JL, Cock ML, McLachlan RI (2011) The prevalence and diagnosis rates of Klinefelter syndrome: an Australian comparison. Med J Aust 194(1):24\u201328","journal-title":"Med J Aust"},{"issue":"2","key":"1816_CR37","doi-asserted-by":"publisher","first-page":"R67","DOI":"10.1530\/EJE-14-0213","volume":"171","author":"I Gies","year":"2014","unstructured":"Gies I, Unuane D, Velkeniers B, De Schepper J (2014) Management of Klinefelter syndrome during transition. Eur J Endocrinol 171(2):R67-77. https:\/\/doi.org\/10.1530\/EJE-14-0213 (Epub 2014 May 6 PMID: 24801585)","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"1816_CR38","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/ajmg.c.31349","volume":"163C","author":"L Aksglaede","year":"2013","unstructured":"Aksglaede L, Link K, Giwercman A, J\u00f8rgensen N, Skakkebaek NE, Juul A (2013) 47, XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management. Am J Med Genet C Semin Med Genet 163C(1):55\u201363. https:\/\/doi.org\/10.1002\/ajmg.c.31349 (Epub 2013 Jan 23 PMID: 23345262)","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"1816_CR39","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1111\/cen.13572","volume":"88","author":"A Garolla","year":"2018","unstructured":"Garolla A, Selice R, Menegazzo M, Valente U, Zattoni F, Iafrate M, Prayer-Galetti T, Gardiman MP, Ferlin A, Di Nisio A, Foresta C (2018) Novelinsights on testicular volume and testosterone replacementtherapy in Klinefelter patients undergoing testicular sperm extraction. A retrospective clinical study. Clin Endocrinol (Oxf) 88:711\u2013718","journal-title":"Clin Endocrinol (Oxf)"},{"key":"1816_CR40","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.metabol.2017.09.017","volume":"86","author":"GA Kanakis","year":"2018","unstructured":"Kanakis GA, Nieschlag E (2018) Klinefelter syndrome: more than hypogonadism. Metabolism 86:135\u2013144","journal-title":"Metabolism"},{"issue":"1","key":"1816_CR41","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/andr.12909","volume":"9","author":"M Zitzmann","year":"2021","unstructured":"Zitzmann M, Aksglaede L, Corona G, Isidori AM, Juul A, T\u2019Sjoen G, Kliesch S, D\u2019Hauwers K, Toppari J, S\u0142owikowska-Hilczer J, T\u00fcttelmann F, Ferlin A (2021) European academy of andrology guidelines on Klinefelter syndrome endorsing organization: European Society of Endocrinology. Andrology 9(1):145\u2013167","journal-title":"Andrology"}],"container-title":["Journal of Endocrinological Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-022-01816-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40618-022-01816-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-022-01816-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T12:29:36Z","timestamp":1661344176000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40618-022-01816-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["1816"],"URL":"https:\/\/doi.org\/10.1007\/s40618-022-01816-4","relation":{},"ISSN":["1720-8386"],"issn-type":[{"value":"1720-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,24]]},"assertion":[{"value":"17 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study has been approved by the ethics committee: n\u00b0 protocol 1489, October 2015.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent has been obtained from the study participants.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}