Growth hormone stimulation tests in pediatrics

The diagnosis of growth hormone deficiency (GHD) in childhood is a multifaceted process requiring comprehensive clinical, auxologic, biochemical tests of the GH-IGF axis, and radiologic evaluations. It is well known that impaired GH responses to provocative tests will show classic GHD. Among classic provocative tests, insulin-induced hypoglycemia (ITT), arginine, and glucagon have been demonstrated to be the most reliable. These tests stimulate GH secretion through actions at the hypothalamic level, but their poor within-subject reproducibility implies low specificity; this evidence recommended that GHD is demonstrated by failure to respond to 2 stimuli to reduce the number of false-positive GHD diagnoses. Growth hormone-releasing hormone (GHRH) testing is not reliable because it is highly variable, reflecting variations in the endogenous somatostatinergic tone. In combination with substances that inhibit or counteract somatostatin (arginine, pyridostigmine, GH secretagogues), GHRH becomes the most potent and reproducible stimulus of GH secretion, exploring the maximal GH secretory capacity and in turn, the appropriately normal function of the hypothalamic network. GHRH + arginine or pyridostigmine tests have high specificity. With appropriate cutoff limits (<20 μg/L in childhood and adolescence), they are as reliable as classic provocative tests to distinguish between normal and GHD subjects. The responses to these tests are reproducible and positively correlated with classic tests. Thus, these tests are reliable alternatives to classic ones for the diagnosis of GHD either in childhood or in the transition adolescent as well as in adulthood.