EVALUATION OF THE CLINICAL UTILITY OF THE ULTRASENSITIVE IMMUNOFLUOMETRIC ASSAY FOR GROWTH-HORMONE (GH) AND OF THE CORTISOL SECRETORY PATTERN IN PREDICTION OF THE LINEAR GROWTH-RESPONSE TO TREATMENT WITH GH

Objectives: To evaluate the utility of an ultrasensitive IFMA for huma n 22 kDa GH in assessment of GH secretion and prediction of the linear growth response to exogenous GH. Methods: Utilizing Delfia reagents s upplied by Wallac-OY, an ultrasensitive IFMA for GH was established. S erum GH concentrations from 15 children/adolescents undergoing 24 hour GH secretory profiles with sampling at 20 minute intervals were analy zed by both IFMA and RIA. Cortisol values were also measured. Twelve c hildren were later treated with GH. The 24 hour GH and cortisol secret ory profiles were analyzed by the Cluster program and the relationship s of these profiles to the linear growth response to exogenous GH dete rmined. Results: The sensitivity of the IFMA for GH relative to a zero standard was 0.005 ng/ml; intra-assay coefficients of variation range d from 12% at a GB concentration of 0.005 ng/ml to 4% at 0.038 ng/ml; interassay coefficients of variation ranged from 34% at a GH concentra tion of 0.005 ng/ml to 10.5% at 2.7 ng/ml and to 2.7% at 12.7 ng/ml. A bove assay sensitivity, there was good correlation between GH concentr ations determined by IFMA and those by IRMA and RTA (r=0.998 and 0.992 respectively). The number of GH secretory peaks identified by IFMA wa s significantly greater than that detected by RIA (10.6 +/- 3.2 [SD] v s 6.7 +/- 3.3/24 hours, p=0.0001 by paired t-test). There were few sig nificant relationships between any parameter of GH secretion measured by RIA or IFMA (peak GH pulse amplitude, percent increase in amplitude , area under the peak, interpeak interval) and the pretreatment growth rate, the growth velocity while receiving GH therapy, or the incremen t in growth rate during administration of GH. The number of GH secreto ry peaks determined by RIA correlated weakly with the pretreatment gro wth rate. There was no meaningful relationship between the serum conce ntrations of cortisol and GH-IFMA. Peak GH concentrations and nadir co rtisol values were exactly coincident in 15.7% (25/159); 42.8% of nadi r cortisol values coincided with or were within +/- 20 minutes of peak GH values (68/159). However, there was no relationship between the nu mber of cortisol secretory peaks, the pooled 24 hour and nocturnal con centrations of cortisol and the pretreatment growth velocity, the grow th rate or increment in growth velocity during administration of GH. C onclusions: Despite the increased sensitivity of the IFMA and its abil ity to detect pulsatile GH secretion heretofore unidentified, data ft om this GH assay were not useful in predicting first year growth rate during administration of GH. The secretory pattern of cortisol was not helpful in predicting the growth response to GH.