Abstract
BACKGROUND—Growth hormone insufficiency (GHI) is diagnosed conventionally by short stature and slow growth, and is confirmed by diminished peak GH response to a provocation test. Insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) have previously been considered individually OBJECTIVE—To test the hypothesis that the combined analysis of IGF-I and IGFBP-3 could act as a surrogate marker for the diagnosis of GHI. DESIGN—Reference ranges for IGF-I and IGFBP-3 were calculated using 521 normal individuals. A retrospective analysis was performed on 318 children referred for investigation of short stature. RESULTS—No significant difference was found between either the IGF-I or IGFBP-3 standard deviation scores (SDSs) in children with and without GHI. If the requirement were for both tests to be positive (< −2 SDS) for a diagnosis of GHI, then 99% of children without GHI would be correctly identified; however, the sensitivity of the test was only 15%. CONCLUSIONS—Neither IGF-I nor IGFBP-3 alone is a marker for GHI. In addition, they cannot be used as an effective screening test in combination.
Full Text
The Full Text of this article is available as a PDF (171.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adan L., Souberbielle J. C., Brauner R. Diagnostic markers of permanent idiopathic growth hormone deficiency. J Clin Endocrinol Metab. 1994 Feb;78(2):353–358. doi: 10.1210/jcem.78.2.7508948. [DOI] [PubMed] [Google Scholar]
- Baxter R. C., Martin J. L. Structure of the Mr 140,000 growth hormone-dependent insulin-like growth factor binding protein complex: determination by reconstitution and affinity-labeling. Proc Natl Acad Sci U S A. 1989 Sep;86(18):6898–6902. doi: 10.1073/pnas.86.18.6898. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blum W. F., Albertsson-Wikland K., Rosberg S., Ranke M. B. Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab. 1993 Jun;76(6):1610–1616. doi: 10.1210/jcem.76.6.7684744. [DOI] [PubMed] [Google Scholar]
- Blum W. F., Ranke M. B., Kietzmann K., Gauggel E., Zeisel H. J., Bierich J. R. A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metab. 1990 May;70(5):1292–1298. doi: 10.1210/jcem-70-5-1292. [DOI] [PubMed] [Google Scholar]
- Cianfarani S., Boemi S., Spagnoli A., Cappa M., Argirò G., Vaccaro F., Manca Bitti M. L., Boscherini B. Is IGF binding protein-3 assessment helpful for the diagnosis of GH deficiency? Clin Endocrinol (Oxf) 1995 Jul;43(1):43–47. doi: 10.1111/j.1365-2265.1995.tb01891.x. [DOI] [PubMed] [Google Scholar]
- Cole T. J. The LMS method for constructing normalized growth standards. Eur J Clin Nutr. 1990 Jan;44(1):45–60. [PubMed] [Google Scholar]
- Dattani M. T., Pringle P. J., Hindmarsh P. C., Brook C. G. What is a normal stimulated growth hormone concentration? J Endocrinol. 1992 Jun;133(3):447–450. doi: 10.1677/joe.0.1330447. [DOI] [PubMed] [Google Scholar]
- Furlanetto R. W., Underwood L. E., Van Wyk J. J., D'Ercole A. J. Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest. 1977 Sep;60(3):648–657. doi: 10.1172/JCI108816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gill M. S., Whatmore A. J., Tillman V., White A., Addison G. M., Price D. A., Clayton P. E. Urinary IGF and IGF binding protein-3 in children with disordered growth. The North West Paediatric Endocrine Group. Clin Endocrinol (Oxf) 1997 Apr;46(4):483–492. doi: 10.1046/j.1365-2265.1997.1670981.x. [DOI] [PubMed] [Google Scholar]
- Hasegawa Y., Hasegawa T., Yokoyama T., Kotoh S., Tsuchiya Y., Kurimoto F. Western ligand blot assay for human growth hormone-dependent insulin-like growth factor binding protein (IGFBP-3): the serum levels in patients with classical growth hormone deficiency. Endocrinol Jpn. 1992 Feb;39(1):121–127. doi: 10.1507/endocrj1954.39.121. [DOI] [PubMed] [Google Scholar]
- Isley W. L., Underwood L. E., Clemmons D. R. Dietary components that regulate serum somatomedin-C concentrations in humans. J Clin Invest. 1983 Feb;71(2):175–182. doi: 10.1172/JCI110757. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Juul A., Holm K., Kastrup K. W., Pedersen S. A., Michaelsen K. F., Scheike T., Rasmussen S., Müller J., Skakkebaek N. E. Free insulin-like growth factor I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency. J Clin Endocrinol Metab. 1997 Aug;82(8):2497–2502. doi: 10.1210/jcem.82.8.4137. [DOI] [PubMed] [Google Scholar]
- Lindsay R., Feldkamp M., Harris D., Robertson J., Rallison M. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. 1994 Jul;125(1):29–35. doi: 10.1016/s0022-3476(94)70117-2. [DOI] [PubMed] [Google Scholar]
- Pringle P. J., Jones J., Hindmarsh P. C., Preece M. A., Brook C. G. Performance of proficiency survey samples in two immunoradiometric assays of human growth hormone and comparison with patients' samples. Clin Chem. 1992 Apr;38(4):553–557. [PubMed] [Google Scholar]
- Rasat R., Livesey J. L., Espiner E. A., Abbott G. D., Donald R. A. IGF-1 and IGFBP-3 screening for disorders of growth hormone secretion. N Z Med J. 1996 May 10;109(1021):156–159. [PubMed] [Google Scholar]
- Rasmussen M. H., Frystyk J., Andersen T., Breum L., Christiansen J. S., Hilsted J. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone. Metabolism. 1994 Mar;43(3):315–319. doi: 10.1016/0026-0495(94)90099-x. [DOI] [PubMed] [Google Scholar]
- Rikken B., van Doorn J., Ringeling A., Van den Brande J. L., Massa G., Wit J. M. Plasma levels of insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein-3 in the evaluation of childhood growth hormone deficiency. Horm Res. 1998 Sep;50(3):166–176. doi: 10.1159/000023268. [DOI] [PubMed] [Google Scholar]
- Rosenfeld R. G., Wilson D. M., Lee P. D., Hintz R. L. Insulin-like growth factors I and II in evaluation of growth retardation. J Pediatr. 1986 Sep;109(3):428–433. doi: 10.1016/s0022-3476(86)80112-3. [DOI] [PubMed] [Google Scholar]
- Shah A., Stanhope R., Matthew D. Hazards of pharmacological tests of growth hormone secretion in childhood. BMJ. 1992 Jan 18;304(6820):173–174. doi: 10.1136/bmj.304.6820.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sox H. C., Jr Probability theory in the use of diagnostic tests. An introduction to critical study of the literature. Ann Intern Med. 1986 Jan;104(1):60–66. doi: 10.7326/0003-4819-104-1-60. [DOI] [PubMed] [Google Scholar]
- Sox H. C. The evaluation of diagnostic tests: principles, problems, and new developments. Annu Rev Med. 1996;47:463–471. doi: 10.1146/annurev.med.47.1.463. [DOI] [PubMed] [Google Scholar]
- Tillmann V., Buckler J. M., Kibirige M. S., Price D. A., Shalet S. M., Wales J. K., Addison M. G., Gill M. S., Whatmore A. J., Clayton P. E. Biochemical tests in the diagnosis of childhood growth hormone deficiency. J Clin Endocrinol Metab. 1997 Feb;82(2):531–535. doi: 10.1210/jcem.82.2.3750. [DOI] [PubMed] [Google Scholar]