Electronic Letters to:

Special Features: P. Cohen, A. D. Rogol, C. L. Deal, P. Saenger, E. O. Reiter, J. L. Ross, S. D. Chernausek, M. O. Savage, J. M. Wit on behalf of the 2007 ISS Consensus Workshop participants Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short Stature: A Summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop J Clin Endocrinol Metab 2008; 93: 4210-4217 [Abstract] [Full text] [PDF]

eLetters: Submit a response to this article

Electronic letters published:

Authors' Response

Pinchas Cohen, Alan D. Rogol, Chery L. Deal, Paul Saenger, Ed O.Reiter, Judith L.Ross, Steven D. Chernausek, Martin O. Savage, Jan-Maarten Wit   (23 January 2009)

Letter to the Editor

Arlan L. Rosenbloom, J. Guevara-Aguirre, M.J. Haller, T.H. Malasanos, J.L. Miller, H.J. Rohrs, D.A. Schatz, J.H. Silverstein, D.A. Weinstein   (14 January 2009)

Authors' Response 23 January 2009
Pinchas Cohen, Professor UCLA, Alan D. Rogol, Chery L. Deal, Paul Saenger, Ed O.Reiter, Judith L.Ross, Steven D. Chernausek, Martin O. Savage, Jan-Maarten Wit Send letter to journal: Re: Authors' Response hassy{at}mednet.ucla.edu Pinchas Cohen, et al.	We thank Dr. Rosenbloom and colleagues for their thoughtful letter with respect to the recently published consensus statement on idiopathic short stature (ISS) (1). The document represents a synthesis of many hours of discussion, research and debate. In addition to representing the thoughts of the participants, all experts in the field, the manuscript has been reviewed and edited by an additional group of senior pediatric endocrinologists on the boards of the LWPES, ESPE, GRS, and other pediatric endocrine societies. Unanimous agreement on every issue did not occur and certain topics remain very controversial, in which case the statement acknowledged both sides of the issue. The main concern raised in this letter is whether constitutional delay of growth and puberty (CDGP) should be considered as a subgroup of ISS, or a separate entity. The majority of the participants voted for the first option, consistent with an earlier expert workshop (2) and the ESPE Classification of Paediatric Endocrine Disorders (3). The arguments in favor of this subgroup option are extensively described in one of the reviews that was used in preparing the ISS Consensus meeting (4). The most important argument for including CDGP in ISS is that before the onset of puberty there can be no certainty that puberty will be normal or delayed. Therefore, at the age that decisions about diagnosis and treatment have to be made, the differentiation between CDGP and non-CDGP cannot be ascertained. At best, a positive family history, a “characteristic” growth pattern, normal stature for skeletal maturation (and thus a predicted adult height close to the mid-parental height) may increase the likelihood of CDGP. However, there is no specific parameter to distinguish the different growth patterns and predicted adult height in either condition (5). Also of note is the fact that most children carrying the diagnosis of CDGP have heights between the 5th and 2.3rd percentile and children who are shorter than the -2 SDS probably represent a different population. Indeed, adult height is below predicted adult height in untreated children with ISS (height <-2.5 SDS) (5) demonstrating that unlike the typical CDGP patients who usually have a normal adult height, this population often does not. The second issue raised was whether priming with sex steroids before GH testing should be recommended. There are good arguments to perform such priming, but in spite of a vigorous discussion at the meeting (many experts felt as Rosenbloom and colleagues do, and even more felt differently); no consensus on this topic was reached. We therefore stated the lack of consensus and decided to leave this decision to the discretion of each pediatric endocrinologist. References 1. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM 2008 Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab 93:4210-4217 2. Ranke MB 1996 Towards a Consensus on the Definition of Idiopathic Short Stature. Summary. Horm Res 45 (suppl 2):64-66 3. Wit JM, Ranke MB, Kelnar CJH 2007 ESPE Classification of Paediatric Endocrine Diagnoses. Horm Res 68(suppl 2):1-120 4. Wit JM, Clayton PE, Rogol AD, Savage MO, Saenger PH, Cohen P 2008 Idiopathic short stature: definition, epidemiology, and diagnostic evaluation. Growth Horm IGF Res 18:89-110 5. Wit JM, Rekers-Mombarg LT 2002 Final height gain by GH therapy in children with idiopathic short stature is dose dependent. J Clin Endocrinol Metab 87:604-611
Letter to the Editor 14 January 2009
Arlan L. Rosenbloom University of Florida, Gainesville, J. Guevara-Aguirre, M.J. Haller, T.H. Malasanos, J.L. Miller, H.J. Rohrs, D.A. Schatz, J.H. Silverstein, D.A. Weinstein Send letter to journal: Re: Letter to the Editor rosenal{at}peds.ufl.edu Arlan L. Rosenbloom, et al.	The participants in the consensus workshop on idiopathic short stature (ISS) are to be commended for undertaking a daunting task (1). Their treatment recommendations for ISS are appropriately conservative, consistent with the paucity of evidence supporting recombinant human growth hormone (rhGH) treatment of ISS recently emphasized in a Cochrane report (2). The consensus report, however, includes recommendations about the use of testosterone and oxandrolone in constitutional delay of growth and puberty (CDGP) that highlight a dissonance in their defining of ISS to include CDGP. They define ISS by a height below -2 SD score without evidence of disease or GH deficiency (GHD). While CDGP, the most common explanation for short stature evaluation in the pediatric endocrinology clinic, may be considered idiopathic, stature is normal for osseous maturation and adult stature is expected to be normal. The consensus definition of ISS without reference to height prognosis contrasts with the FDA indications for treatment of ISS with rhGH, which include growth rate unlikely to result in normal adult height. Disregarding critical dynamic and prognostic criteria led to the inappropriate inclusion of CDGP as a category of ISS (1). This is not simply a pedantic taxonomic issue, but as the consensus document notes, dictates very different counseling and treatment consideration for CDGP than for ISS. Obfuscating the distinction between ISS and CDGP supports attempts to treat CDGP with rhGH by applying the rather liberal criteria from the FDA approval of rhGH therapy for ISS, as those who review insurance appeals will attest. This adds to the longer standing inappropriate treatment of CDGP with GH by the misdiagnosis of GHD. Misdiagnosis is the result of non-evidence-based criteria for GH response that has served to label many normal children as GHD and fails to recognize the high frequency of poor response to stimulation in normal prepubertal children. There is little value in GH testing of children at TS 1-3 unless they are primed with sex steroids (3). This is likely to be the explanation why 70-75% of patients treated for isolated non-organic GHD in childhood have normal GH responses when retested after adolescence (4, 5). It is also regrettable, therefore, that the consensus document dismissed sex steroid priming for ruling out GHD with the non sequitor "country dependent,” rather than embracing it as one of the few evidence-based statements that could be made about diagnosis of growth disorders. References 1. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM, on behalf of the 2007 ISS consensus workshop participants. 2008 Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology workshop. J Clin Endocrinol Metab 93:4210-4217 2. Bryant J, Baxter L, Cave CB, Milne R. 2007 Recombinant growth hormone for idiopathic short stature in children and adolescents (Review) The Cochrane Library, Issue 3. Art. No.: CD004440. DOI: 10.1002/14651858.CD004440.pub2 3. Marin G, Domené HM, Barnes KM, Blackwell BJ, Cassorla FG, Cutler Jr GB. 1994 The effects of estrogen priming and puberty on the growth hormone response to standardize treadmill exercise and arginine insulin in normal girls and boys. J Clin Endocrinol Metab 79:537-541 4. Tauber M, Moulin P, Pienkowski C, Jouret B, Rochiccioli P. 1997 Growth hormone (GH) retesting and auxological data of 131 GH-deficient patients after completion of treatment. J Clin Endocrinol Metab 82: 349-351 5. Bonfig W, Chechtold S, Bachmann S, Putzker S, Fuchs O, Pagel P, Schwartz HP. 2008 Reassessment of the optimal growth hormone cutoff level in insulin tolerance testing for growth hormone secretion in patients with childhood onset growth hormone deficiency during transition to adulthood. J Pediatr Endocrinol Metab 21:1049-1055