This Article Full Text Full Text (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 Tillmann, V. Articles by Clayton, P. E. Search for Related Content PubMed PubMed Citation Articles by Tillmann, V. Articles by Clayton, P. E.

Biochemical Tests in the Diagnosis of Childhood Growth Hormone Deficiency¹

Royal Manchester Children’s Hospital, Christie Hospital (S.M.S.), Manchester; Sheffield Children’s Hospital (J.K.W.), Sheffield; General Infirmary (J.M.B.), Leeds; and South Cleveland Hospital (M.S.K.), Middlesbrough, United Kingdom

Address all correspondence and requests for reprints to: Dr. Peter E. Clayton, Department of Endocrinology, Royal Manchester Children’s Hospital, Manchester, M27 4HA, UK.

GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. We have examined, therefore, the performance of other tests of the GH axis [urinary GH excretion, serum insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) levels] compared with GH stimulation tests in identifying children defined clinically as GH deficient.

Group I comprised 60 children (mean age, 10.3 ± 4.8 yr) whose diagnosis of GHD was based on a medical history indicative of pituitary dysfunction (n = 43) or on the typical phenotypic features and appropriate auxological characteristics of isolated GHD (n = 17). Group II comprised 110 short children (mean age, 9.8 ± 4 yr) in whom GHD was not suspected, but needed exclusion.

The best sensitivity for a single GH test was 85% at a peak GH cut-off level of 10 ng/mL, whereas the best specificity was 92% at 5 ng/mL. The sensitivities of IGF-I, IGFBP-3, and urinary GH, using a cut-off of -2 SD score were poor at 34%, 22%, and 25%, respectively, with specificities of 72%, 92%, and 76% respectively. Only 2 of 21 pubertal children in group I and none of the 27 subjects with radiation-induced GHD had an IGFBP-3 SD score less than -1.5. We devised a scoring system based on the positive predictive value of each test, incorporating data from the GH test and the IGF-I and IGFBP-3 levels. A specificity of 94% could be achieved with a score of 10 or more (maximum 17) (sensitivity 34%). The latter could not be improved above 81% with a score of 5 points or more (specificity, 69%).

A high score was, therefore, highly indicative of GHD, but was achieved by few patients. A normal IGFBP-3 level, however, did not exclude GHD, particularly in patients with radiation-induced GHD and those in puberty. A GH test with a peak level more than 10 ng/mL was the most useful single investigation to exclude a diagnosis of GHD.

This article has been cited by other articles:

				B. P Hauffa, N. Lehmann, M. Bettendorf, O. Mehls, H.-G. Dorr, N. Stahnke, H. Steinkamp, E. Said, M. B Ranke, and participating members of the German KIGS Board/Med Central laboratory reassessment of IGF-I, IGF-binding protein-3, and GH serum concentrations measured at local treatment centers in growth-impaired children: implications for the agreement between outpatient screening and the results of somatotropic axis functional testing Eur. J. Endocrinol., November 1, 2007; 157(5): 597 - 603. [Abstract] [Full Text] [PDF]

				S. Zucchini, P. Pirazzoli, F. Baronio, M. Gennari, M. O. Bal, A. Balsamo, S. Gualandi, and A. Cicognani Effect on Adult Height of Pubertal Growth Hormone Retesting and Withdrawal of Therapy in Patients with Previously Diagnosed Growth Hormone Deficiency J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4271 - 4276. [Abstract] [Full Text] [PDF]

				A. J Drake and C. J H Kelnar The evaluation of growth and the identification of growth hormone deficiency Arch. Dis. Child. Ed. Pract., October 1, 2006; 91(3): ep61 - ep67. [Full Text] [PDF]

				S. Cianfarani, A. Liguori, S. Boemi, M. Maghnie, L. Iughetti, M. Wasniewska, M. E. Street, S. Zucchini, G. Aimaretti, and D. Germani Inaccuracy of Insulin-Like Growth Factor (IGF) Binding Protein (IGFBP)-3 Assessment in the Diagnosis of Growth Hormone (GH) Deficiency from Childhood to Young Adulthood: Association to Low GH Dependency of IGF-II and Presence of Circulating IGFBP-3 18-Kilodalton Fragment J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6028 - 6034. [Abstract] [Full Text] [PDF]

				J. Bjork, K. Link, and E. M. Erfurth The Utility of the Growth Hormone (GH) Releasing Hormone-Arginine Test for Diagnosing GH Deficiency in Adults with Childhood Acute Lymphoblastic Leukemia Treated with Cranial Irradiation J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6048 - 6054. [Abstract] [Full Text] [PDF]

				C. Lofqvist, E. Andersson, L. Gelander, S. Rosberg, L. Hulthen, W. F. Blum, and K. A. Wikland Reference Values for Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) and the Ratio of Insulin-Like Growth Factor-I to IGFBP-3 throughout Childhood and Adolescence J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1420 - 1427. [Abstract] [Full Text] [PDF]

				T J Cole, P C Hindmarsh, and D B Dunger Growth hormone (GH) provocation tests and the response to GH treatment in GH deficiency Arch. Dis. Child., November 1, 2004; 89(11): 1024 - 1027. [Abstract] [Full Text] [PDF]

				H. R. Boquete, P. G. V. Sobrado, H. L. Fideleff, A. M. Sequera, A. V. Giaccio, M. G. Suarez, G. F. Ruibal, and M. Miras Evaluation of Diagnostic Accuracy of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3 in Growth Hormone-Deficient Children and Adults Using ROC Plot Analysis J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4702 - 4708. [Abstract] [Full Text] [PDF]

				R. I. G. Holt, E. Webb, C. Pentecost, and P. H. Sonksen Aging and Physical Fitness Are More Important Than Obesity in Determining Exercise-Induced Generation of GH J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5715 - 5720. [Abstract] [Full Text] [PDF]

				C. Lofqvist, E. Andersson, L. Gelander, S. Rosberg, W. F. Blum, and K. A. Wikland Reference Values for IGF-I throughout Childhood and Adolescence: A Model that Accounts Simultaneously for the Effect of Gender, Age, and Puberty J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5870 - 5876. [Abstract] [Full Text] [PDF]

				L. Adan, C. Trivin, C. Sainte-Rose, J. M. Zucker, O. Hartmann, and R. Brauner GH Deficiency Caused by Cranial Irradiation during Childhood: Factors and Markers in Young Adults J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5245 - 5251. [Abstract] [Full Text] [PDF]

				W. M. Drake, S. J. Howell, J. P. Monson, and S. M. Shalet Optimizing GH Therapy in Adults and Children Endocr. Rev., August 1, 2001; 22(4): 425 - 450. [Abstract] [Full Text] [PDF]

				A. S. MartÍnez, H. M. Domené, M. G. Ropelato, H. G. Jasper, P. A. Pennisi, M. E. Escobar, and J. J. Heinrich Estrogen Priming Effect on Growth Hormone (GH) Provocative Test: A Useful Tool for the Diagnosis of GH Deficiency J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4168 - 4172. [Abstract] [Full Text]

				B BIELINSKI, N J SHAW, and P M CLARK IGFBP-3 as a predictor of growth hormone deficiency Arch. Dis. Child., March 1, 2000; 82(3): 266k - 266. [Full Text]

				H. Guyda Four Decades of Growth Hormone Therapy for Short Children: What Have We Achieved? J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4307 - 4316. [Full Text]

				Somatostatin Infusion Withdrawal: Studies in Normal Children and in Children with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4426 - 4430. [Abstract] [Full Text]

				M. H. Aguiar-Oliveira, M. S. Gill, E. S. de, A. Barretto, M. R. S. Alcântara, F. Miraki-Moud, C. A. Menezes, A. H. O. Souza, C. E. Martinelli, F. A. Pereira, et al. Effect of Severe Growth Hormone (GH) Deficiency due to a Mutation in the GH-Releasing Hormone Receptor on Insulin-Like Growth Factors (IGFs), IGF-Binding Proteins, and Ternary Complex Formation Throughout Life J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4118 - 4126. [Abstract] [Full Text]

				J. Khosravi, A. Diamandi, J. Mistry, and R. G. Krishna The High Molecular Weight Insulin-Like Growth Factor-Binding Protein Complex: Epitope Mapping, Immunoassay, and Preliminary Clinical Evaluation J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2826 - 2833. [Abstract] [Full Text]

				H Mitchell, M T Dattani, V Nanduri, P C Hindmarsh, M A Preece, and C G D Brook Failure of IGF-I and IGFBP-3 to diagnose growth hormone insufficiency Arch. Dis. Child., May 1, 1999; 80(5): 443 - 447. [Abstract] [Full Text]

				N. Kawai, S. Kanzaki, S. Takano-Watou, C. Tada, Y. Yamanaka, T. Miyata, M. Oka, and Y. Seino Serum Free Insulin-Like Growth Factor I (IGF-I), Total IGF-I, and IGF-Binding Protein-3 Concentrations in Normal Children and Children with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 82 - 89. [Abstract] [Full Text]

				R. L. Hintz The Role of Auxologic and Growth Factor Measurements in the Diagnosis of Growth Hormone Deficiency Pediatrics, August 1, 1998; 102(2): 524 - 526. [Abstract] [Full Text]

				S. M. Shalet, A. Toogood, A. Rahim, and B. M. D. Brennan The Diagnosis of Growth Hormone Deficiency in Children and Adults Endocr. Rev., April 1, 1998; 19(2): 203 - 223. [Abstract] [Full Text]