Background: In Prader-Willi syndrome (PWS) a reduced growth hormone (GH) response to several stimulators has been documented in many studies, but none have focused on very young children. We evaluated the pattern of GH secretion in very young PWS patients. Patients and Methods: Twenty-seven genetically confirmed PWS children (10 females, aged 0.4-5 years, mean: 2.2 ± 1.4 years) were included. All subjects underwent standard provocative tests (clonidine, CLO; and arginine, ARG) and one combined test [growth hormone-releasing hormone (GHRH) plus pyridostigmine (13 patients) or GHRH plus arginine (14 patients)]. Insulin-like growth factor-1 (IGF-1) levels were also measured. Results: While standard tests (CLO and ARG) showed low GH peak in 85.2 and 70.4% of the patients, respectively, the combined test was found to be normal in 85.2%. IGF-1 was low in 66.7% of patients. Out of 27 patients, 3 (11%) showed a normal GH peak with both standard tests (group A), 6 (22%) to one of the standard tests (group B) and 18 (67%) presented a low response to both standard tests (group C). Four subjects showed low response to both the combined and standard tests and reduced IGF-1. Conclusion: Our data suggest that very young PWS children seem to have impaired hypothalamic GHRH secretion with a normal GH pituitary reserve.

Whittington JE, Holland AJ, Webb T, Butler J, Clarke D, Boer H: Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet 2001;38:792-798.
Grugni G, Crinò A, Bosio L, Corrias A, Cuttini M, De Toni T, Di Battista E, Franzese A, Gargantini L, Greggio N, Iughetti L, Livieri C, Naselli A, Pagano C, Pozzan G, Ragusa L, Salvatoni A, Trifirò G, Beccaria L, Bellizzi M, Bellone J, Brunani A, Cappa M, Caselli G, Cerioni V, Delvecchio M, Giardino D, Iannì F, Memo L, Pilotta A, Pomara C, Radetti G, Sacco M, Sanzari A, Sartorio A, Tonini G, Vettor R, Zaglia F, Chiumello G; Genetic Obesity Study Group of Italian Society of Pediatric Endocrinology and Diabetology (ISPED): The Italian National Survey for Prader-Willi syndrome: an epidemiologic study. Am J Med Genet A 2008;146:861-872.
Bittel DC, Butler MG: Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med 2005;7:1-20.
Goldstone AP: Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab 2004;15:12-20.
Crinò A, Di Giorgio G, Livieri C, Crinò A, Di Giorgio G, Livieri C, Grugni G, Beccaria L, Bosio L, Corrias A, Chiumello G, Trifirò G, Salvatoni A, Tonini G, Gargantini L, de Toni T, Valerio G, Ragusa L, Franzese A, Rinaldi MM, Spera S, Gattinara GC, Villani S, Iughetti L; Genetic Obesity Study Group; Italian Society of Pediatric Endocrinology and Diabetology: A survey on Prader-Willi syndrome in the Italian population: prevalence of historical and clinical signs. J Pediatr Endocrinol Metab 2009;22:883-893.
Cassidy SB, Schwartz S, Miller JL, Driscoll DJ: Prader-Willi syndrome. Genet Med 2012;14:10-26.
Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M; speakers contributors at the Second Expert Meeting of the Comprehensive Care of Patients with PWS: Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab 2008;93:4183-4197.
Angulo M, Castro-Magana M, Mazur B, Canas JA, Vitollo PM, Sarrantonio M: Growth hormone secretion and effects of growth hormone therapy on growth velocity and weight gain in children with Prader-Willi syndrome. J Pediatr Endocrinol Metab 1996;9:393-400.
Corrias A, Bellone J, Beccaria L, Bosio L, Trifirò G, Livieri C, Ragusa L, Salvatoni A, Andreo M, Ciampalini P, Tonini G, Crinò A: GH/IGF-1 axis in Prader-Willi syndrome: evaluation of IGF-1 levels and of the somatotroph responsiveness to various provocative stimuli. Genetic Obesity Study Group of Italian Society of Pediatric Endocrinology and Diabetology. J Endocrinol Invest 2000;23:84-89.
Burman P, Ritzen EM, Lindgren AC: Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH. Endocr Rev 2001;22:787-799.
Diene G, Mimoun E, Feigerlova E, Caula S, Molinas C, Grandjean H, Tauber M: French Reference Centre for PWS: endocrine disorders in children with Prader-Willi syndrome: data from 142 children of the French database. Horm Res Paediatr 2010;74:121-128.
Tauber M, Cutfield W: KIGS highlights: growth hormone treatment in Prader-Willi syndrome. Horm Res 2007;68(suppl 5):48-50.
Growth Hormone Research Society Consensus guidelines for the diagnosis and treatment of GH deficiency in childhood and adolescence: summary statement of the Growth Hormone Research Society. J Clin Endocrinol Metab 2000;85:3990-3993.
Aimaretti G, Bellone S, Baffoni C, Cornel G, Origlia C, Di Vito L, Rovere S, Arvat E, Camanni F, Ghigo E: Short procedure of GHRH plus arginine test in clinical practice. Pituitary 2001;4:129-134.
Giacomozzi C, Spadoni L, Pedicelli S, Scirè G, Cristofori L, Peschiaroli E, Deodati A, Cambiaso P, Cappa M, Cianfarani S: Responses to GHRH plus arginine test are more concordant with IGF-1 circulating levels than responses to arginine and clonidine provocative tests. J Endocrinol Invest 2012;35:742-747.
Maghnie M, Salati B, Bianchi S, Rallo M, Tinelli C, Autelli M, Aimaretti G, Ghigo E: Relationship between the morphological evaluation of the pituitary and the growth hormone (GH) response to GH-releasing hormone plus arginine in children and adults with congenital hypopituitarism. J Clin Endocrinol Metab 2001;86:1574-1579.
Maghnie M, Cavigioli F, Tinelli C, Autelli M, Aricò M, Aimaretti G, Ghigo E: GHRH plus arginine in the diagnosis of acquired GH deficiency of childhood-onset. J Clin Endocrinol Metab 2002;87:2740-2744.
Corneli G, Di Somma C, Baldelli R, Rovere S, Gasco V, Croce CG, Grottoli S, Maccario M, Colao A, Lombardi G, Ghigo E, Camanni F, Aimaretti G: The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Eur J Endocrinol 2005;153:257-264.
Grugni G, Guzzaloni G, Moro D, Bettio D, De Medici C, Morabito F: Reduced growth hormone (GH) responsiveness to combined GH-releasing hormone and pyridostigmine administration in the Prader-Willi syndrome. Clin Endocrinol 1998;48:769-775.
Holm VA, Cassidy SB, Butler MG, Hanchett JM, Greenswag LR, Whitman BY, Greenberg F: Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 1993;91:398-402.
Tanner JM, Whitehouse RH: Clinical longitudinal standards for height, weight, height velocity, weight velocity and stages of puberty. Arch Dis Child 1976;51:170-179.
Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR: 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11 2002;246:1-190.
Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A: Italian cross-sectional growth charts for height, weight and BMI (2 to 20 years). J Endocrinol Invest 2006;29:581-593.
Bedogni G, Giannone G, Maghnie M, Giacomozzi C, Di Iorgi N, Pedicelli S, Peschiaroli E, Melioli G, Muraca M, Cappa M, Cianfarani S: Serum insulin-like growth factor-I (IGF-I) reference ranges for chemiluminescence assay in childhood and adolescence: data from a population of in- and out-patients. Growth Horm IGF Res 2012;22:134-138.
Devesa J, Lima L, Lois N, Fraga C, Lechuga MJ, Arce V, Tresguerres JA: Reasons for the variability in the growth hormone (GH) responses to GHRH challenge: the endogenous hypothalamic-somatotroph rhythm (HSR). Clin Endocrinol 1989;30:367-377.
Cappa M, Grossi A, Borrelli P, Ghigo E, Bellone J, Benedetti S, Carta D, Loche S: Growth hormone (GH) response to combined pyridostigmine and GH-releasing hormone administration in patients with Prader-Labhard-Willi syndrome. Horm Res 1993;39:51-55.
Beccaria L, Benzi F, Sanzari A, Bosio L, Brambilla P, Chiumello G: Impairment of growth hormone responsiveness to growth hormone releasing hormone and pyridostigmine in patients affected by Prader-Labhardt-Willi syndrome. J Endocrinol Invest 1996;19:687-692.
Grugni G, Marzullo P, Ragusa L, Sartorio A, Trifirò G, Liuzzi A, Crinò A; Genetic Obesity Study Group of the Italian Society of Pediatric Endocrinology and Diabetology: Impairment of GH responsiveness to combined GH-releasing hormone and arginine administration in adult patients with Prader-Willi syndrome. Clin Endocrinol 2006;65:492-499.
Grugni G, Crinò A, Bertocco P, Marzullo P: Body fat excess and stimulated growth hormone levels in adult patients with Prader-Willi syndrome. Am J Med Genet A 2009;149:726-731.
Grugni G, Crinò A, Pagani S, Meazza C, Buzi F, De Toni T, Gargantini L, Pilotta A, Pozzan GB, Radetti G, Ragusa L, Salvatoni A, Sartorio A, Bozzola M; Genetic Obesity Study Group, Italian Society of Pediatric Endocrinology and Diabetology: GH secretory pattern in non-obese children and adolescents with Prader-Willi syndrome. J Ped Endocrinol Metab 2011;24:477-481.
Fillion M, Deal CL, Van Vliet G: Normal minipuberty of infancy in boys with Prader-Willi syndrome. J Pediatr 2006;149:874-876.
Corrias A, Grugni G, Crinò A, Di Candia S, Chiabotto P, Cogliardi A, Chiumello G, De Medici C, Spera S, Gargantini L, Iughetti L, Luce A, Mariani B, Ragusa L, Salvatoni A, Andrulli S, Mussa A, Beccaria L; Study Group for Genetic Obesity of Italian Society of Pediatric Endocrinology and Diabetology: Assessment of central adrenal insufficiency in children and adolescents with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2012;76:843-850.
Grugni G, Beccaria L, Corrias A, Crinò A, Cappa M, De Medici C, Di Candia S, Gargantini L, Ragusa L, Salvatoni A, Sartorio A, Spera S, Andrulli S, Chiumello G, Mussa A; The Genetic Obesity Study Group of the Italian Society of Pediatric Endocrinology Diabetology (ISPED): Central adrenal insufficiency in young adults with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2013;79:371-378.
Eiholzer U, Bachmann S, l'Allemand D: Is there growth hormone deficiency in Prader-Willi syndrome? Horm Res 2000;53(suppl 3):44-52.
Stanley TL, Levitsky LL, Grinspoon SK, Misra M: Effect of body mass index on peak growth hormone response to provocative testing in children with short stature. J Clin Endocrinol Metab 2009;94:4875-4881.
Deal CL, Tony M, Höybye C, Allen DB, Tauber M, Christiansen JS; 2011 Growth Hormone in Prader-Willi Syndrome Clinical Care Guidelines Workshop Participants: Growth Hormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin Endocrinol Metab 2013;98:E1072-E1087.
Qu XD, Gaw Gonzalo IT, Al Sayed MY, Cohan P, Christenson PD, Swerdloff RS, Kelly DF, Wang C: Influence of body mass index and gender on growth hormone (GH) responses to GH-releasing hormone plus arginine and insulin tolerance tests. J Clin Endocrinol Metab 2005;90:1563-1569.
Whitman B, Carrel A, Becx T, et al: Growth hormone improves body composition and motor development in infants with Prader-Willy syndrome after six months. J Ped Endocrinol Metab 2004;17:591-600.
Oto Y, Obata K, Matsubara K, Kozu Y, Tsuchiya T, Sakazume S, Yoshino A, Muratami N, Ogata T, Nagai T: Growth hormone secretion and its effect on height in pediatric patients with different genotypes of Prader-Willi syndrome. Am J Med Genet Part A 2012;158A:1477-1480.
Gunay-Aygun M, Schwartz S, Heeger S, O'Riordan MA, Cassidy SB: The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics 2001;108:E92.
Grugni G, Marostica E, Crinò A, Marzullo P, De Nicolao G, Sartorio A: Deconvolution-based assessment of pituitary GH secretion stimulated with GHRH + arginine in Prader-Willi adults and obese controls. Clin Endocrinol (Oxf) 2013;79:224-231.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.