Rapid Responses to:

EDITORIALS: Paul Saenger Growth hormone in growth hormone deficiency BMJ 2002; 325: 58-59 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Growth hormone in growth hormone deficiency: ignore the evidence and keep going wrong

Jean-Claude Carel, Emmanuel Ecosse, Joël Coste   (14 August 2002)

Growth hormone in growth hormone deficiency: ignore the evidence and keep going wrong 14 August 2002
Jean-Claude Carel, Professor of Paediatrics Pediatric Endocrinology, GH Cochin - Saint Vincent de Paul, 75014 Paris, France, Emmanuel Ecosse, Joël Coste Send response to journal: Re: Growth hormone in growth hormone deficiency: ignore the evidence and keep going wrong	Dear Sirs, We read with interest and surprise the editorial (1) to our paper (2), challenging our conclusions that most patients treated for growth hormone deficiency do not in fact, have this condition, and that controlled trials should be organized to evaluate the long term effects of growth hormone in most of the patients currently treated. Dr Saenger supports the use of an integrated approach to the diagnosis of growth hormone deficiency and of wider use of IGF-1 measurements, as suggested by the Growth Hormone Research Society consensus (3). However, the recent publications by Dr Saenger, as coauthor (4) or as senior author (5) do not reflect his plea, as patients with growth hormone deficiency were essentially defined by short stature and peak growth hormone levels below 10 ng/mL. This contradiction reflects the widespread contrast between the recommendations made by consensus guidelines and current practice, or clinical research protocols. Dr Saenger (1) argues for a continuum of growth hormone secretion ranging from a moderate deficiency to a severe one and advocates the use of IGF-1 measurements. However, IGF-1 levels mostly reflect food intake (6) and are poorly discriminative in "moderate growth hormone deficiency" (if such a condition does exist). Our previous analysis of growth hormone stimulation tests (7) and our recent paper (2) support the use of these tests when appropriate thresholds are used: below 2 to 4 ng/ml using the older polyclonal assays (equivalent to ? 1 to 3 ng/ml using the newer monoclonal assays). These thresholds perfectly match the lower values observed in normal children (8;9). Therefore, the main problem with growth hormone stimulation tests is with their use that has led to a wider diagnosis of idiopathic growth hormone deficiency. In the absence of a gold standard, how can we define growth hormone deficiency? We propose the use of long-term results of treatment in comparison with spontaneous outcome as a gold standard and our results indicate that most patients had no clear benefit. Dr Saenger argues that the patients in our paper were not treated for long enough and therefore do not provide long term results of growth hormone treatment. He contrasts our results with those reported by Blethen et al on 121 patients from the National Cooperative Growth Study (NCGS) database (10). In these patients, the mean duration of treatment was 6.2 years, compared with 3.2 years in our report. However, the 121 patients analysed represent less than 1% of approximately 14 000 patients who had started treatment that are included in the database. We included all patients who had started treatment in the analysis to calculate the mean duration of treatment. If we had only selected the 1% of patients with the longest treatment duration, our mean treatment duration would have been 7.9 years! We thought that we had made it clear in our paper that reports focusing on patients with longer treatments give a biased and overoptimistic view of the results. Obviously we were not clear enough for the invited editorialist. Finally, we agree with Dr Saenger that you can draw an analogy between the real estate business and growth hormone use: better location in real estate and longer duration of treatment with growth hormone both mean higher costs. However, a good location in real estate generally results in a good long-term investment whereas the result of long-term growth hormone treatment is still debatable . Reference List 1. Saenger P. Growth hormone in growth hormone deficiency. Start treatment early and give it for long enough. BMJ 2002;325:58-9. 2. Carel JC, Ecosse E, Nicolino M, Tauber M, Leger J, Cabrol S, Bastié-Sigeac I, Chaussain JL, Coste J. Adult height after long-term recombinant growth hormone treatment for idiopathic isolated growth hormone deficiency: observational follow-up study of the French population-based registry. BMJ 2002;325:70-3. 3. GH Research Society. Consensus. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH research society. J.Clin.Endocrinol.Metab. 2000;85:3990-89. 4. Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J, and the Genentech Icsg. High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. J.Clin.Endocrinol.Metab. 2000;85:3653-60. 5. Reiter EO, Attie KM, Moshang T Jr, Silverman BL, Kemp SF, Neuwirth RB, Ford KM, Saenger P. A multicenter study of the efficacy and safety of sustained release GH in the treatment of naive pediatric patients with GH deficiency. J Clin Endocrinol Metab 2001;86:4700-6. 6. Frasier SD. Editorial: the diagnosis and treatment of childhood and adolescent growth hormone deficiency--consensus or confusion? J Clin Endocrinol Metab 2000;85:3988-9. 7. Carel JC, Tresca J-P, Letrait M, Le Bouc Y, Job J-C, Chaussain JL, Coste J. Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J.Clin.Endocrinol.Metab. 1997;82:2117-21. 8. Ghigo E, Bellone J, Aimaretti G, Bellone S, Loche S, Cappa M, Bartolotta E, Dammaco F, Camani F. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J.Clin.Endocrinol.Metab. 1996;81:3323-7. 9. Marin G, Domené HM, Barnes KM, Blackwell BJ, Cassorla FG, Cutler GBJ. The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill excercise and arginine-insulin in normal girls and boys. J.Clin.Endocrinol.Metab. 1994;79:537-41. 10. Blethen SL, Baptista J, Kuntze J, Foley T, LaFranchi S, Johanson A. Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. The Genentech Growth Study Group. J.Clin.Endocrinol.Metab. 1997;82:418-20.