Comparison of nocturnal and morning ghrelin concentration in children with growth hormone deficiency and with idiopathic short stature

Abstract

Ghrelin - a growth hormone (GH) secretagogue - presents a circadian rhythm with higher nocturnal than diurnal concentration (similar to GH). However, daily ghrelin production depends on food intake and nutritional state; it is increased in the fasting state and decreased after a meal. Since most past research concerning short stature children has relied on the morning ghrelin concentration for analyses, we decided to assess ghrelin concentration at the 60^th and 90^th minute after falling asleep and in the morning at 06:00 h, shortly after waking up from nighttime sleep (after 12 h of fasting). We compared these ghrelin concentrations to determine differences between nocturnal and morning ghrelin release in short children, both with idiopathic short stature (ISS) and growth hormone deficiency (GHD). We also analyzed the correlation between the nocturnal and morning ghrelin concentrations with nocturnal GH concentrations, measured at the same time points, as well as with maximal GH concentration, achieved by stimulation tests, and with the insulin-like growth factor I (IGF-I). The ghrelin and GH concentration 60^th and 90^th minute after falling asleep, as well as fasting morning ghrelin and IGF-I concentrations, were measured in 19 (n = 10 ISS and n = 9 GHD) prepubertal short children (7 girls and 12 boys), aged 10.36 ± 3.06 y. Differences between the nocturnal and morning ghrelin concentrations were analyzed by the Wilcoxon matched-pairs signed-rank test. Typical regression and correlation analyses were used to assess relationships among parametric data for other analyses. The Wilcoxon test showed ghrelin concentration is significantly higher in the morning than both at the 60^th and 90^th minute after falling asleep time points (in ISS and GHD). A significant correlation was observed: a) positive - between nocturnal ghrelin (both at the 60^th and 90^th minute) and morning ghrelin concentrations; b) positive - between ghrelin at the 60^th minute and nocturnal GH concentrations (both at the 60^th and 90^th minute); c) negative - between ghrelin at the 60^th minute and IGF-I concentrations; and d) negative - between body mass index and ghrelin concentrations at the 60^th and 90^th minute. We conclude: 1) in short children, both with GHD and with ISS, morning ghrelin level reflects its nocturnal concentration; however, it is significantly higher than the nocturnal ones. There is no significant difference between the measurement of ghrelin concentration at night at the 60^th or 90^th minute after falling asleep; 2) morning ghrelin concentration is affected by the hunger and satiety; therefore, it appears that nocturnal measurements better reflect the pool of hormone responsible for stimulation of GH and IGF-I secretion, especially since positive correlation between nocturnal ghrelin and nocturnal GH secretion was noted; 3) it seems that a higher body mass index is an additional independent factor, associated mainly with lower nocturnal (but not morning) ghrelin secretion.

Keywords: Circadian rhythms; children; ghrelin; growth hormone deficiency; idiopathic short stature; insulin-like growth factor I.