Biochemical tests in the diagnosis of childhood growth hormone deficiency

• Published in: The journal of clinical endocrinology and metabolism Vol. 82; no. 2; pp. 531 - 535
• Main Authors: TILLMANN, V, BUCKLER, J. M. H, KIBIRIGE, M. S, PRICE, D. A, SHALET, S. M, WALES, J. K. H, ADDISON, M. G, GILL, M. S, WHATMORE, A. J, CLAYTON, P. E
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-02-1997
• Subjects: Adolescent; Biochemistry - methods; Biological and medical sciences; Child; Endocrinopathies; Female; Human Growth Hormone - deficiency; Human Growth Hormone - secretion; Human Growth Hormone - urine; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - analysis; Male; Medical sciences; Metabolism, Inborn Errors - blood; Metabolism, Inborn Errors - diagnosis; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Endocrinopathy; Human; Urine; Protein hormone; Biochemical analysis; Adenohypophyseal hormone; Deficiency; STH; Diagnosis; Hormonal investigation; Child; Blood plasma
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.82.2.531

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.