Skip to main content
NCBI home page
The BMJ logoLink to The BMJ
. 2002 Nov 2;325(7371):1037. doi: 10.1136/bmj.325.7371.1037/c

Growth hormone in growth hormone deficiency

Ignore the evidence and keep going wrong

Jean-Claude Carel 1, Emmanuel Ecosse 1, Joël Coste 1
PMCID: PMC1124510  PMID: 12411378

Editor—We were surprised that in his editorial to our paper Saenger challenged our conclusions that most patients treated for growth hormone deficiency do not have this condition, and that controlled trials should be organised to evaluate the long term effects of growth hormone in most of the patients currently treated.1 Saenger supports the use of an integrated approach to diagnosing growth hormone deficiency and the wider use of IGF-1 measurements, as suggested by the Growth Hormone Research Society. However, his recent publications, as coauthor or senior author, do not reflect his plea.2,3 This contradiction reflects the widespread contrast between the recommendations in consensus guidelines and current practice or clinical research protocols.

In the absence of a gold standard, how can growth hormone deficiency be defined? We propose using long term results of treatment in comparison with spontaneous outcome. The results of our observational study indicate that most patients had no clear benefit. 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 in 121 patients from the national cooperative growth study database, who were treated for a mean of 6.2 years compared with 3.2 years in our report.4

We included all patients who had started treatment to calculate its mean duration, whereas the 121 patients analysed represent less than 1% of around 14 000 patients in the national cooperative growth study. If we had selected only 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 not clearly enough.

We agree with Saenger that you can draw an analogy between the real estate business and use of growth hormone: better location in real estate and longer duration of growth hormone treatment 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.

References

  • 1.Saenger P. Growth hormone in growth hormone deficiency. BMJ. 2002;325:58–59. doi: 10.1136/bmj.325.7355.58. . (13 July.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J 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;85:3653–3660. doi: 10.1210/jcem.85.10.6906. [DOI] [PubMed] [Google Scholar]
  • 3.Reiter EO, Attie KM, Moshang T, Jr, Silverman BL, Kemp SF, Neuwirth RB, et al. 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;86:4700–4706. doi: 10.1210/jcem.86.10.7932. [DOI] [PubMed] [Google Scholar]
  • 4.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;82:418–420. doi: 10.1210/jcem.82.2.3734. [DOI] [PubMed] [Google Scholar]
BMJ. 2002 Nov 2;325(7371):1037.

Deficiency cannot be diagnosed solely on the results of stimulation tests

Sandro Loche 1,2,3, Mohamad Maghnie 1,2,3, Marco Cappa 1,2,3

Editor—We agree with Carel that many children treated for idiopathic growth hormone deficiency do not have this condition.1-1 We found that most children with idiopathic growth hormone deficiency had a normal growth hormone response in stimulation tests when retested at the attainment of final height.1-2 Only patients with growth hormone deficiency whose results on magnetic resonance imaging showed anatomical abnormalities of the hypothalamic-pituitary area had permanent growth hormone deficiency. All the others had normal growth hormone secretion at retesting.

Furthermore, we recently found that among 33 prepubertal children with a biochemical diagnosis of growth hormone deficiency (a growth hormone response to two stimulation tests <10 μ/l), 28 had a normal response when retested after two to six months.1-3 Normalisation of the growth hormone response to stimulation occurred irrespective of the time interval from the first evaluation and was not related to puberty since none of our patients had entered puberty before re-evaluation. This finding does not support the concept of a transient growth hormone secretory defect that improves with the pubertal secretion of sex steroids.

We and others have shown that concentrations of IGF-1 and IGFBP-3 are invariably reduced in patients with severe, unequivocal growth hormone deficiency.1-2,1-4 This indicates that subnormal concentrations of IGF-1 and IGFBP-3 can be considered diagnostic of growth hormone deficiency, provided other causes of reduced IGF-1 or IGFBP-3 such as malnutrition, hypothyroidism, renal failure, and diabetes are excluded. This observation, coupled with the fact that IGF-1 concentrations do not correlate with the results of growth hormone stimulation tests,1-3,1-4 implies inadequate assessment of growth hormone secretion and emphasises the need for careful evaluation of short children and eventual revision of the current diagnostic criteria.

Although biochemical tests for growth hormone secretion clearly distinguish children with severe growth hormone deficiency of pituitary origin, recognition of more subtle forms of growth hormone insufficiency still represents a diagnostic dilemma. Idiopathic growth hormone deficiency cannot be diagnosed solely on the results of stimulation tests but requires evaluation of multiple biochemical and clinical or auxological variables.

We are convinced that patients with pathological growth hormone responses to provocative tests but normal results on magnetic resonance scans of the hypothalamic-pituitary area should be re-evaluated and followed up before a diagnosis of growth hormone deficiency is firmly established.

References

  • 1-1.Carel JC, Ecosse E, Nicolino M, Tauber M, Leger J, Cabrol S, et al. Adult height after long term treatment with recombinant growth hormone for idiopathic growth hormone deficiency: observational follow-up of the French population based registry. BMJ. 2002;325:70–76. doi: 10.1136/bmj.325.7355.70. . (13 July.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-2.Maghnie M, Strigazzi C, Tinelli C, Autelli M, Cisternino M, Loche S, et al. Growth hormone deficiency (GHD) of childhood onset: reassessment of GH status and evaluation of the predictive criteria for permanent GHD in young adults. J Clin Endocrinol Metab. 1999;84:1324–1328. doi: 10.1210/jcem.84.4.5614. [DOI] [PubMed] [Google Scholar]
  • 1-3.Loche S, Bizzarri C, Maghnie M, Faedda A, Tzialla C, Autelli M, et al. Results of early re-evaluation of growth hormone (GH) secretion in short children with apparent GH deficiency. J Pediatr. 2002;140:445–449. doi: 10.1067/mpd.2002.122729. [DOI] [PubMed] [Google Scholar]
  • 1-4.Rosenfeld RG, Albertsson-Wikland K, Cassorla F, Frasier SD, Hasegawa Y, Hinz RL, et al. Diagnostic controversy: the diagnosis of childhood growth hormone deficiency revisited. J Clin Endocrinol Metab. 1995;80:1532–1540. doi: 10.1210/jcem.80.5.7538145. [DOI] [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES