Growth hormone response to hexarelin, growth hormone-releasing hormone plus pyridostigmine and arginine plus estrogen in prepubertal and early pubertal short children.
BACKGROUND
Hexarelin (HEX), a synthetic hexapeptide with a strong GH-stimulating activity, has been suggested as a stimulus for evaluating GH secretion. However, in childhood it has never been compared with other stimuli capable to reduce the effect of the somatostatinergic tone and of the low production of gonadal steroids.


METHODS
We evaluated GH response (expressed as the maximum value after stimulus [Cmax] and as area under the curve [AUC], mean +/- SD) to HEX at a dose of 2 micrograms/kg i.v., in comparison with those obtained after GHRH (1 microgram/kg i.v.) + pyridostigmine (PD, 60 mg p.o.) and arginine + ethynylestradiol (E2, 1 mg/day p.o. for 3 days before the test), in 5 subjects with familial short stature (FSS), 11 with constitutional growth delay (CGD), prepubertal (Tanner's stage I) and early pubertal (stage II), and in 8 healthy children age-matched as controls.


RESULTS
HEX induced a Cmax of 31.9 +/- 18.4 micrograms/l and an AUC of 1511 +/- 923 micrograms/min x l in stage I, of 36.7 +/- 12.3 micrograms/l and 1938 +/- 903 micrograms/min x l in stage II (ns). GHRH + PD induced a Cmax of 33.8 +/- 14.6 micrograms/l and an AUC of 2072 +/- 1233 micrograms/min x l in stage I, of 29.6 +/- 15.6 micrograms/l and 1901 +/- 1252 micrograms/min x l in stage II (ns). ARG + E2 induced a Cmax of 17.8 +/- 7 micrograms/l and an AUC of 1157 +/- 505 micrograms/min x l in stage I, of 15.6 +/- 11.6 micrograms/l and 649 +/- 452 micrograms/min x l in stage II (ns). The Cmax of HEX was higher than that of ARG + E2 in both stages I and II (p < 0.05); AUC of HEX, was higher than that of ARG + E2 only in stage II (p < 0.01); the Cmax and the AUC of GHRH + PD were higher than those of ARG + E2 both in stage I (p < 0.01 and p < 0.05, respectively) and in stage II (p < 0.05). No difference, neither in the extent of GH response to HEX and GHRH + PD nor in that to stimuli between subjects and controls, was found. HEX has given 32% false positives in stage I and 17% in stage II, GHRH + PD 12% and 15%, while ARG + E2 provided 20% in stage I and 32% in stage II. On the whole, specificity was 76% for HEX and ARG + E2 and 89% for GHRH + PD.


CONCLUSIONS
HEX induced greater GH response than that of ARG + E2 but similar to that of GHRH + PD and its specificity was not different to that of ARG + E2 and lower than that of GHRH + PD: then its use does not show a diagnostic advantage in respect to the other two stimuli in peripubertal age.
Guzzaloni
G
G
Istituto Auxologico Italiano, IRCCS, Ospedale S. Giuseppe, Divisione di Auxologia, Verbania Intra.
Grugni
G
G
Morabito
F
F
D000293:Adolescent; D019540:Area Under Curve; D001120:Arginine; D002648:Child; D004347:Drug Interactions; D004967:Estrogens; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000175:diagnosis*; D013007:Growth Hormone-Releasing Hormone; D006133:Growth Substances; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D008297:Male; D009842:Oligopeptides; D011627:Puberty; D011729:Pyridostigmine Bromide
D004967:Estrogens; D006133:Growth Substances; D009842:Oligopeptides; C086184:hexarelin; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; D011729:Pyridostigmine Bromide