Combining insulin-like growth factor-I and mean spontaneous nighttime growth hormone levels for the diagnosis of growth hormone deficiency.

There is no gold standard for the diagnosis of GH deficiency. Recent data show that spontaneous GH levels may lack sensitivity, and that GH stimulation tests lack specificity as currently performed. Serum insulin-like growth factor-I (IGF-I) measurements lack both sensitivity and specificity. Some of these problems may be explained by nutritional effects. In children, overnutrition decreases GH and increases IGF-I, while undernutrition decreases IGF-I and increases GH. To overcome these difficulties and improve diagnostic accuracy, we combined mean spontaneous nighttime GH levels with IGF-I levels in a statistically based bivariate model. On a two-dimensional plot of mean spontaneous nighttime GH level (in SD units) vs. IGF-I level (in SD units), we defined a new variable, S (sum) score, where S = (1/square root of 2) x (nighttime mean GH SD+IGF-I SD). While IGF-I (SD) and the mean spontaneous nighttime GH (SD) showed a significant correlation with body mass index, the S score was independent of body mass. We, therefore, used the S score to define a new test for GH deficiency. A child failed this bivariate test if his S score was less than -2 SD. We applied this model to 47 normal children and 48 short or slowly growing children (all prepubertal). We measured spontaneous nighttime GH levels and IGF-I levels in all children. In addition, the short children underwent 3 GH stimulation tests. Forty-six of the 47 normal children passed the bivariate test for GH sufficiency. Twenty-three of the 48 short or slowly growing children failed the bivariate test, whereas only 11 children had an abnormally low mean spontaneous nighttime GH measurement alone. Sixteen of 23 children who were GH deficient by the bivariate test were also GH deficient by the stimulation tests. In summary, the bivariate test for GH deficiency appears 1) to be independent of body mass, unlike either IGF-I or GH individually; 2) to identify more children than the mean spontaneous nighttime GH level alone; and 3) to be highly specific in the normal population, unlike stimulation tests.