{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T21:06:37Z","timestamp":1781039197449,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T00:00:00Z","timestamp":1548201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"World Association of Infectious Diseases and Immunological Disorders","award":["Grant n. WAidid2017_05"],"award-info":[{"award-number":["Grant n. WAidid2017_05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>To investigate growth hormone (GH) secretion at the transition age, retesting of all subjects who have undergone GH replacement therapy is recommended when linear growth and pubertal development are complete to distinguish between transitional and persistent GH deficiency (GHD). Early retesting of children with idiopathic and isolated GHD (i.e., before the achievement of final height and\/or the adult pubertal stage) can avoid possible over-treatment. Here, we report data from our population with idiopathic and isolated GHD to encourage changes in the management and timing of retesting. We recruited 31 patients (19 males) with idiopathic GHD who received recombinant GH (rGH) for at least 2 years. All of the patients were retested at the transition age at least 3 months after rGH discontinuation. Permanent GHD was defined as a GH peak of &lt;19 ng\/mL after administration of growth hormone\u2013releasing hormone (GHRH) + arginine as a provocative test. Permanent GHD was confirmed in only five of 31 patients (16.13%). None of these patients presented low serum insulin-like growth factor (IGF)-1 levels (&lt;\u22122 standard deviation score (SDS)). Only one male patient with an IGF-1 serum level lower than \u22122 SDS showed a normal GH stimulation response, with a GH peak of 44.99 ng\/mL. Few patients with idiopathic and isolated GHD demonstrated persistence of the deficit when retested at the transition age, suggesting that the timing of retesting should be anticipated to avoid overtreatment.<\/jats:p>","DOI":"10.3390\/ijerph16030307","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T11:12:48Z","timestamp":1548328368000},"page":"307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Growth Hormone (GH) Therapy During the Transition Period: Should We Think about Early Retesting in Patients with Idiopathic and Isolated GH Deficiency?"],"prefix":"10.3390","volume":"16","author":[{"given":"Laura","family":"Penta","sequence":"first","affiliation":[{"name":"Paediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Cofini","sequence":"additional","affiliation":[{"name":"Paediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lucchetti","sequence":"additional","affiliation":[{"name":"Paediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Zenzeri","sequence":"additional","affiliation":[{"name":"Paediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Leonardi","sequence":"additional","affiliation":[{"name":"Paediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Lanciotti","sequence":"additional","affiliation":[{"name":"Paediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Galeazzi","sequence":"additional","affiliation":[{"name":"Paediatric Unit, Narni Hospital, 05035 Narni (PG), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Verrotti","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-2837","authenticated-orcid":false,"given":"Susanna","family":"Esposito","sequence":"additional","affiliation":[{"name":"Paediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1159\/000452150","article-title":"Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency","volume":"86","author":"Grimberg","year":"2016","journal-title":"Horm. Res. Paediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1530\/eje.1.01829","article-title":"Consensus statement on the management of the GH-treated adolescent in the transition to adult care","volume":"152","author":"Clayton","year":"2005","journal-title":"Eur. J. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1097\/MOP.0000000000000505","article-title":"Growth hormone treatment for growth hormone deficiency and idiopathic short stature: new guidelines shaped by the presence and absence of evidence","volume":"29","author":"Grimberg","year":"2017","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1159\/000071230","article-title":"The Transition from Adolescence to Adult Life: Physiology of the \u201cTransition\u201d Phase and Its Evolutionary Basis","volume":"60","author":"Rosenfeld","year":"2003","journal-title":"Horm. Res. Paediatr."},{"key":"ref_5","first-page":"257","article-title":"The contributions of growth and puberty to peak bone mass","volume":"55","author":"Gordon","year":"1991","journal-title":"Growth Dev. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1172\/JCI117034","article-title":"Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model","volume":"93","author":"Matkovic","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1210\/jcem.85.5.6598","article-title":"Continuation of growth hormone (GH) therapy in GH-deficient patients during transition from childhood to adulthood: Impact on insulin sensitivity and substrate metabolism","volume":"85","author":"Vahl","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1210\/jcem.85.5.6598","article-title":"Continuation of growth hormone (GH) replacement in GH-deficient patients during transition from childhood to adulthood: A two-year placebo-controlled study","volume":"85","author":"Vahl","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5273","DOI":"10.1210\/jc.2003-030204","article-title":"Growth Hormone (GH) Dose-Response in Young Adults with Childhood-Onset GH Deficiency: A Two-Year, Multicenter, Multiple-Dose, Placebo-Controlled Study","volume":"88","author":"Underwood","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4857","DOI":"10.1210\/jc.2004-0551","article-title":"Continued Growth Hormone (GH) treatment after final height is necessary to complete somatic development in childhood-onset GH-deficient patients","volume":"89","author":"Attanasio","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1210\/jc.2003-031588","article-title":"Comparison of continuation or cessation of growth hormone (GH) therapy on body composition and metabolic status in adolescents with severe GH deficiency at completion of linear growth","volume":"89","author":"Carroll","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1210\/jcem.86.10.7897","article-title":"GH is needed for the maturation of muscle mass and strength in adolescents","volume":"86","author":"Bengtsson","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1210\/jc.2002-021541","article-title":"The effect of cessation of growth hormone (GH) therapy on bone mineral accretion in GH-deficient adolescents at the completion of linear growth","volume":"88","author":"Drake","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ghir.2007.04.010","article-title":"Growth hormone replacement throughout life: Insights into age-related responses to treatment","volume":"17","author":"Clayton","year":"2007","journal-title":"Growth Horm. IGF Res."},{"key":"ref_15","first-page":"1284","article-title":"Pitfalls in diagnosing impaired growth hormone (GH) secretion: Retesting after replacement therapy of 63 patients defined as GH deficient","volume":"74","author":"Cacciari","year":"1992","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1056\/NEJM199402173300704","article-title":"Brief report: Hypothyroidism caused by chronic autoimmune thyroiditis in very young infants","volume":"330","author":"Foley","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/BF03344156","article-title":"Italian Cross Sectional Growth Charts for Height Weight and BMI(2 To 20Yr)","volume":"29","author":"Cacciari","year":"2006","journal-title":"J. Endocrinol. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1210\/jcem.82.7.4101","article-title":"Editorial: Why retest young adults with childhood-onset growth hormone deficiency?","volume":"82","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1210\/jcem.84.4.5614","article-title":"Growth hormone (GH) deficiency (GHD) of childhood onset: Reassessment of GH status and evaluation of the predictive criteria for permanent GHD in young adults","volume":"84","author":"Maghnie","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1210\/jc.2009-0602","article-title":"Reassessment of the growth hormone status in young adults with childhood-onset growth hormone deficiency: Reappraisal of insulin tolerance testing","volume":"94","author":"Secco","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","first-page":"1244","article-title":"Reevaluation of growth hormone (GH) secretion in 69 adults diagnosed as GH-deficient patients during childhood","volume":"81","author":"Longobardi","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1046\/j.1365-2265.1996.00850.x","article-title":"Normal growth hormone secretion in growth hormone insufficient children retested after completion of linear growth","volume":"45","author":"Wacharasindhu","year":"1996","journal-title":"Clin. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1210\/jcem.82.2.3726","article-title":"Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment","volume":"82","author":"Tauber","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","first-page":"3693","article-title":"Retesting young adults with childhood-onset growth hormone (GH) deficiency with GH-releasing-hormone-plus-arginine test","volume":"85","author":"Aimaretti","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1055\/s-0032-1327599","article-title":"Changes in BMI and Management of Patients with Childhood Onset Growth Hormone Deficiency in the Transition Phase","volume":"120","author":"Sievers","year":"2012","journal-title":"Exp. Clin. Endocrinol. Diabetes."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1136\/adc.44.235.291","article-title":"Variations in Pattern of Pubertal Changes in Girls","volume":"44","author":"Marshall","year":"1969","journal-title":"Arch. Disease Child."},{"key":"ref_27","first-page":"61","article-title":"Testicular volume during adolescence. Cross-sectional and longitudinal studies","volume":"29","author":"Zachmann","year":"1974","journal-title":"Helv. Paediatr. Acta"},{"key":"ref_28","unstructured":"Agency, I.M. (2019, January 23). Gazzetta Ufficiale Della Repubblica Italiana. Available online: https:\/\/www.unisa.it\/AREAVII\/banche_dati\/banche_descrizioni\/gazzetta_ufficiale_della_repubblica_italiana."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/BF03343686","article-title":"Sequential administration of arginine and arginine plus GHRH to test somatotroph function in short children","volume":"23","author":"Bellone","year":"2000","journal-title":"J. Endocrinol. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1530\/EJE-12-0801","article-title":"Magnetic resonance imaging of CNS in 15,043 children with GH deficiency in KIGS (Pfizer International Growth Database)","volume":"168","author":"Maghnie","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000350829","article-title":"Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: Data from an international observational study","volume":"79","author":"Deal","year":"2013","journal-title":"Horm. Res. Paediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1365-2265.2011.04238.x","article-title":"The use of neuroimaging for assessing disorders of pituitary development","volume":"76","author":"Iorgi","year":"2012","journal-title":"Clin. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1530\/EJE-07-0384","article-title":"Cut-off limits of the GH response to GHRH plus arginine test and IGF-I levels for the diagnosis of GH deficiency in late adolescents and young adults","volume":"157","author":"Corneli","year":"2007","journal-title":"Eur. J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/BF03345298","article-title":"Magnetic resonance imaging of hypothalmus-pituitary unitin children suspected of hypopituitarism: How, how and when to investigated","volume":"27","author":"Maghnie","year":"2004","journal-title":"J. Endocrinol. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1210\/jcem.87.7.8593","article-title":"Body composition, IGF-I and IGFBP-3 concentrations as outcome measures in severely GH-deficient (GHD) patients after childhood GH treatment: A comparison with adult onset GHD patients","volume":"87","author":"Attanasio","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fendo.2013.00034","article-title":"The challenge of growth hormone deficiency diagnosis and treatment during the transition from puberty into adulthood","volume":"4","author":"Inzaghi","year":"2013","journal-title":"Front. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/S1096-6374(03)00067-4","article-title":"Transition to the adult endocrine clinic: Testing pituitary function\u2014What tests and when?","volume":"13","author":"Geffner","year":"2003","journal-title":"Growth Horm. IGF Res."},{"key":"ref_38","first-page":"22","article-title":"The regulation of pubertal growth","volume":"60","author":"Styne","year":"2003","journal-title":"Horm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1210\/jc.2011-0179","article-title":"Evaluation and treatment of adult growth hormone deficiency: An endocrine society clinical practice guideline","volume":"96","author":"Molitch","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s40618-014-0201-7","article-title":"Growth hormone treatment of adolescents with growth hormone deficiency (GHD) during the transition period: Results of a survey among adult and paediatric endocrinologists from Italy. Endorsed by SIEDP\/ISPED, AME, SIE, SIMA","volume":"38","author":"Aimaretti","year":"2015","journal-title":"J. Endocrinol. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1054\/ghir.1998.0085","article-title":"Differences in reproducibility and peak growth hormone responses to repeated testing with various stimulators in healthy adults","volume":"9","author":"Hoeck","year":"1999","journal-title":"Growth Horm. IGF Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1530\/eje.0.1350568","article-title":"Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan","volume":"135","author":"Valetto","year":"1996","journal-title":"Eur. J. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ghir.2016.02.001","article-title":"Evaluation of the GHRH-arginine retest for young adolescents with childhood-onset GH deficiency","volume":"27","author":"Dreismann","year":"2016","journal-title":"Growth Horm. IGF Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1136\/archdischild-2014-307228","article-title":"Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence: Table 1","volume":"101","author":"Murray","year":"2016","journal-title":"Arch. Dis. Child."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1210\/jc.2008-1333","article-title":"The effects of central adiposity on growth hormone (GH) response to GH-releasing hormone-arginine stimulation testing in men","volume":"93","author":"Makimura","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ghir.2017.05.003","article-title":"Clinical and laboratory parameters predicting a requirement for the reevaluation of growth hormone status during growth hormone treatment: Retesting early in the course of GH treatment","volume":"34","author":"Vuralli","year":"2017","journal-title":"Growth Horm. IGF Res."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/3\/307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:28:16Z","timestamp":1760185696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/3\/307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,23]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["ijerph16030307"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16030307","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,23]]}}}