Growth delay after liver transplantation in childhood: studies of underlying mechanisms.

After liver transplantation in children, growth is often impaired, but the underlying mechanisms are unknown. Glucocorticoids used for immunosuppression are believed to be partly responsible. After renal transplantation in children, reduced growth hormone (GH) secretion and increased serum insulin-like growth factor-binding protein-3 (IGFBP-3) levels have been reported. We attempted to find endocrine factors predicting growth in 18 prepubertal children followed for more than 1 y (mean 2.4 y) after liver transplantation. Spontaneous and stimulated GH secretion, serum IGF-I, IGFBP-3 concentrations, and endogenous cortisol production were measured. GH secretion was reduced in only two patients. Serum IGF-I concentration was normal, but serum IGFBP-3 was elevated or 1 SD above the mean for age in 62% of the patients. Endogenous cortisol production was reduced in most patients during the first year and improved later in only a few. Growth velocity after transplantation did not correlate with GH secretion, serum IGF-I or IGFBP-3 concentration, or with methylprednisolone dose, but correlated positively with serum basal (rs = 0.44, p < 0.05) and stimulated (rs = 0.53, p < 0.005) cortisol concentration. In conclusion, after liver transplantation 1) the normal pulsatile character of nocturnal GH secretion is sustained, and the GH response to stimulation is reduced in only a few patients; 2) serum IGF-I concentrations are normal; 3) serum IGFBP-3 concentrations are elevated or in the upper part of the normal range in most patients; and 4) endogenous cortisol production is reduced in most patients and correlates positively with growth velocity.