This Article Full Text Full Text (PDF) All Versions of this Article: 90/9/5188    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart 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 Quigley, C. A. Articles by Cutler, G. B. Search for Related Content PubMed PubMed Citation Articles by Quigley, C. A. Articles by Cutler, G. B., Jr. Related Collections Neuroendocrinology and Pituitary Pediatric Endocrinology

Safety of Growth Hormone Treatment in Pediatric Patients with Idiopathic Short Stature

Lilly Research Laboratories, Eli Lilly and Co. (C.A.Q., A.M.G., B.J.C., K.R., J.J.C., A.M.W., G.B.C.), Indianapolis, Indiana 46285; Cincinnati Children’s Hospital Medical Center and University of Cincinnati (S.R.R.), Cincinnati, Ohio 45229; Thomas Jefferson University (J.L.R.), Philadelphia, Pennsylvania 19107; Institute of Maternal and Child Research, University of Chile (F.G.C.), Santiago, Chile; and Leiden University Medical Center (J.M.W., L.T.M.R.-M.), Leiden, The Netherlands

Address all correspondence and requests for reprints to: Dr. Charmian A. Quigley, Lilly Research Laboratories, D/C 5015, Indianapolis, Indiana 46285. E-mail: qac{at}lilly.com.

Context: Recombinant human GH was approved by the United States Food and Drug Administration in 2003 for the treatment of idiopathic short stature (ISS). However, to date, the safety of GH in this patient population has not been rigorously studied.

Objective: The objective of this study was to address the safety of GH treatment in children with ISS compared with GH safety in patient populations for which GH has been approved previously: Turner syndrome (TS) and GH deficiency (GHD).

Design/Setting: The rates of serious adverse events (SAEs) and adverse events (AEs) of particular relevance to GH-treated populations were compared across the three patient populations among five multicenter GH registration studies.

Patients: Children with ISS, TS, or GHD were studied.

Intervention: Treatment consisted of GH doses ranging from 0.18–0.37 mg/kg·wk.

Main Outcome Measures: The main outcome measures were rates of SAEs and AEs of special relevance to patients receiving GH. Laboratory measures of carbohydrate metabolism were used as outcome measures for the ISS studies.

Results: Within the ISS studies, comprising one double-blind, placebo-controlled study and one open-label, dose-response study, SAEs (mainly hospitalizations for accidental injury or acute illness unrelated to GH exposure) were reported for 13–14% of GH-treated patients. Overall AE rates (serious and nonserious) as well as rates of potentially GH-related AEs were similar in the GHD, TS, and ISS studies (for ISS studies combined: otitis media, 8%; scoliosis, 3%; hypothyroidism, 0.7%; changes in carbohydrate metabolism, 0.7%; hypertension, 0.4%). Measures of carbohydrate metabolism were not affected by GH treatment in patients with ISS. There was no significant GH effect on fasting blood glucose in either study (GH dose range, 0.22–0.37 mg/kg·wk) or on insulin sensitivity (placebo-controlled study only).

Conclusion: GH appears safe in ISS; however, the studies were not powered to assess the frequency of rare GH-related events, and longer-term follow-up studies of GH-treated patients with ISS are warranted.

This article has been cited by other articles:

				W. F. Blum, B. J. Crowe, C. A. Quigley, H. Jung, D. Cao, J. L. Ross, L. Braun, G. Rappold, and for the SHOX Study Group Growth Hormone Is Effective in Treatment of Short Stature Associated with Short Stature Homeobox-Containing Gene Deficiency: Two-Year Results of a Randomized, Controlled, Multicenter Trial J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 219 - 228. [Abstract] [Full Text] [PDF]

				L. Dunkel Management of children with idiopathic short stature Eur. J. Endocrinol., November 1, 2006; 155(suppl_1): S35 - S38. [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]

				M. M. Lee Clinical practice. Idiopathic short stature. N. Engl. J. Med., June 15, 2006; 354(24): 2576 - 2582. [Full Text] [PDF]

				J. M. Lee, M. M. Davis, S. J. Clark, T. P. Hofer, and A. R. Kemper Estimated Cost-effectiveness of Growth Hormone Therapy for Idiopathic Short Stature Arch Pediatr Adolesc Med, March 1, 2006; 160(3): 263 - 269. [Abstract] [Full Text] [PDF]

				S. K. Varma Long-Term Growth Hormone Treatment of Idiopathic Short Stature AAP Grand Rounds, January 1, 2006; 15(1): 9 - 10. [Full Text] [PDF]

				B. J. Crowe, L. T. M. Rekers-Mombarg, K. Robling, A. M. Wolka, G. B. Cutler Jr., J. M., and Wit for the European Idiopathic Short Stature Grou Effect of Growth Hormone Dose on Bone Maturation and Puberty in Children with Idiopathic Short Stature J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 169 - 175. [Abstract] [Full Text] [PDF]