This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carrel, A. L. Articles by Allen, D. B. Search for Related Content PubMed PubMed Citation Articles by Carrel, A. L. Articles by Allen, D. B.

Benefits of Long-Term GH Therapy in Prader-Willi Syndrome: A 4-Year Study

Department of Pediatrics (A.L.C., D.B.A.), University of Wisconsin Children’s Hospital, Madison, Wisconsin 53792; and Department of Pediatrics (S.E.M., B.Y.W.), St. Louis University, Cardinal Glennon Children’s Hospital, St. Louis, Missouri 63104

Address all correspondence and requests for reprints to: Aaron L. Carrel, M.D., H4/444 CSC-Pediatrics, University of Wisconsin Hospital and Clinics, 600 Highland Avenue, Madison, Wisconsin 53792. E-mail: . alcarrel{at}facstaff.wisc.edu

Abstract

Obesity, poor growth, and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a GH-deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. While short-term benefits of treatment with GH have been shown, whether these beneficial effects are dose dependent and persist or wane with prolonged therapy remains uncertain. Effects of 24 additional months of GH treatment at varying doses (0.3, 1.0, and 1.5 mg/m²·d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 46 children with PWS, who had previously been treated with GH therapy (1 mg/m²·d) for 12–24 months. Percent body fat, lean muscle mass, and bone mineral density (BMD) were measured by dual x-ray absorptiometry. Indirect calorimetry was used to determine REE and to calculate respiratory quotient. A modified Bruininks-Oseretski test of physical performance evaluated strength and agility. During months 24–48 of GH therapy, continued beneficial effects on body composition (decrease in fat mass and increase in lean body mass), growth velocity, and REE occurred with GH therapy doses of 1.0 and 1.5 mg/m²·d (P < 0.05), but not with 0.3 mg/m²·d. BMD continued to improve at all doses of GH (P < 0.05). Prior improvements in strength and agility that occurred during the initial 24 months were sustained but did not improve further during the additional 24 months regardless of dose. Salutary and sustained GH-induced changes in growth, body composition, BMD, and physical function in children with PWS can be achieved with daily administration of GH doses 1 mg/m². Lower doses of GH, (0.3 mg/m²·d) effective in improving body composition in GHD adults, do not appear to be effective in children with PWS at sustaining improvement in body composition.

This article has been cited by other articles:

				R. F. A. de Lind van Wijngaarden, E. P. C. Siemensma, D. A. M. Festen, B. J. Otten, E. G. A. H. van Mil, J. Rotteveel, R. J. H. Odink, G. C. B. Bindels-de Heus, M. van Leeuwen, D. A. J. P. Haring, et al. Efficacy and Safety of Long-Term Continuous Growth Hormone Treatment in Children with Prader-Willi Syndrome J. Clin. Endocrinol. Metab., November 1, 2009; 94(11): 4205 - 4215. [Abstract] [Full Text] [PDF]

				M. Misra, D. K Katzman, J. Cord, S. J Manning, D. Mickley, D. B Herzog, K. K Miller, and A. Klibanski Percentage extremity fat, but not percentage trunk fat, is lower in adolescent boys with anorexia nervosa than in healthy adolescents Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1478 - 1484. [Abstract] [Full Text] [PDF]

				G. P. August, S. Caprio, I. Fennoy, M. Freemark, F. R. Kaufman, R. H. Lustig, J. H. Silverstein, P. W. Speiser, D. M. Styne, and V. M. Montori Prevention and Treatment of Pediatric Obesity: An Endocrine Society Clinical Practice Guideline Based on Expert Opinion J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4576 - 4599. [Abstract] [Full Text] [PDF]

				A. P. Goldstone, A. J. Holland, B. P. Hauffa, A. C. Hokken-Koelega, M. Tauber, and on behalf of speakers contributors at the Second E Recommendations for the Diagnosis and Management of Prader-Willi Syndrome J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4183 - 4197. [Abstract] [Full Text] [PDF]

				H. R. Mogul, P. D. K. Lee, B. Y. Whitman, W. B. Zipf, M. Frey, S. Myers, M. Cahan, B. Pinyerd, and A. L. Southren Growth Hormone Treatment of Adults with Prader-Willi Syndrome and Growth Hormone Deficiency Improves Lean Body Mass, Fractional Body Fat, and Serum Triiodothyronine without Glucose Impairment: Results from the United States Multicenter Trial J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1238 - 1245. [Abstract] [Full Text] [PDF]

				D. S. Hardin, S. F. Kemp, and D. B. Allen Twenty Years of Recombinant Human Growth Hormone in Children: Relevance to Pediatric Care Providers Clinical Pediatrics, May 1, 2007; 46(4): 279 - 286. [Abstract] [PDF]

				P. Marzullo, C. Marcassa, R. Campini, E. Eleuteri, A. Minocci, A. Sartorio, R. Vettor, A. Liuzzi, and G. Grugni Conditional Cardiovascular Response to Growth Hormone Therapy in Adult Patients with Prader-Willi Syndrome J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1364 - 1371. [Abstract] [Full Text] [PDF]

				B. P. Hauffa, K. Haase, I. M. Range, N. Unger, K. Mann, and S. Petersenn The Effect of Growth Hormone on the Response of Total and Acylated Ghrelin to a Standardized Oral Glucose Load and Insulin Resistance in Children with Prader-Willi Syndrome J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 834 - 840. [Abstract] [Full Text] [PDF]

				D. B. Allen Growth Hormone Therapy for Short Stature: Is the Benefit Worth the Burden? Pediatrics, July 1, 2006; 118(1): 343 - 348. [Full Text] [PDF]

				J. Miller, J. Silverstein, J. Shuster, D. J. Driscoll, and M. Wagner Short-Term Effects of Growth Hormone on Sleep Abnormalities in Prader-Willi Syndrome J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 413 - 417. [Abstract] [Full Text] [PDF]

				S. E. McCandless Prader-Willi Syndrome: A Neonatology Success Story NeoReviews, December 1, 2005; 6(12): e559 - e566. [Full Text] [PDF]

				N. Bridges New indications for growth hormone Arch. Dis. Child. Ed. Pract., June 1, 2005; 90(1): ep7 - ep9. [Full Text] [PDF]

				M. Misra, K. K. Miller, C. Almazan, M. Worley, D. B. Herzog, and A. Klibanski Hormonal Determinants of Regional Body Composition in Adolescent Girls with Anorexia Nervosa and Controls J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2580 - 2587. [Abstract] [Full Text] [PDF]