The efficacy of existing laboratory testing for the diagnosis of childhood growth hormone deficiency needs clarification. Growth hormone stimulation tests are widely used; however, they are associated with a high false-positive rate. Serum insulin-like growth factor I (IGF-I) levels are low in children with growth hormone deficiency but can overlap levels in short normal and normal children. The specificity of this test alone is only 54 percent. Insulin-like growth factor-binding protein-3 (IGFBP-3), the major serum carrier protein for circulating insulin-like growth factors, is regulated by growth hormones and has been reported as having good sensitivity and specificity for the diagnosis of growth hormone deficiency in some studies and poor performance in others. Clinical evaluation remains the most important aspect of assessment in growth disorders. Tillmann and associates compared the value of growth hormone stimulation tests with that of a single serum IGF-I level, IGFBP-3 level and urinary growth hormone level, using the clinical diagnosis of growth disorder as the base standard.
Two groups of children, one with clinically suspected growth hormone deficiency and another with simple short stature, underwent a growth hormone stimulation test and analysis of serum IGF-I and IGFBP-3 concentrations. Urinary growth hormone was measured by an overnight sample collected in the morning.
Using the clinical evaluation (based on history, physical examination and growth parameters) as the "gold standard," a single peak growth hormone concentration using a cut-off of 7.5 ng per mL (7.5 [micro]g per L) proved to have the highest efficiency (81 percent) of all the tests. However, the test had a false-positive rate of 15 percent and a false-negative rate of 27 percent. The alternative tests, when used alone proved less reliable.
An IGFBP-3 level had a high specificity (92 percent) but a poor sensitivity. The finding of a low IGFBP-3 seemed to be highly suggestive of growth hormone deficiency; however, a significant number of children with a definitive diagnosis of growth hormone deficiency had normal IGFBP-3 concentrations.
The authors conclude that a single growth hormone test is the best biochemical tool to evaluate children with growth failure, but it can be more effective when combined with a single serum IGF-I and IGFBP-3 measurement in children whose peak growth hormone levels fall below 10 ng per mL (10 [micro]g per L).
Tillmann V, et al. Biochemical tests in the diagnosis of childhood growth hormone deficiency. J Clin Endocrinol Metab 1997:82:531-5.
COPYRIGHT 1997 American Academy of Family Physicians
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