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Growth delay after liver transplantation in childhood: studies of underlying mechanisms
S Sarna1, I Sipilä, E Vihervuori
1Children's Hospital, University of Helsinki, Finland.
Insights
Pediatric liver transplant recipients show impaired growth, but endocrine factors like reduced cortisol production, not growth hormone (GH) or IGF-I, predict growth velocity post-transplant.
Area of Science:
- Pediatric Endocrinology
- Transplantation Medicine
- Growth and Development
Background:
- Impaired growth is common after pediatric liver transplantation, with unknown mechanisms.
- Glucocorticoids for immunosuppression and altered endocrine function, including growth hormone (GH) and insulin-like growth factor-binding protein-3 (IGFBP-3), are suspected contributors.
- Previous studies in renal transplant recipients noted reduced GH secretion and elevated IGFBP-3.
Purpose of the Study:
- To identify endocrine factors that predict growth in prepubertal children after liver transplantation.
- To investigate the relationship between growth velocity and GH secretion, IGF-I, IGFBP-3, and endogenous cortisol production.
Main Methods:
- Longitudinal follow-up of 18 prepubertal children for over 1 year (mean 2.4 years) post-liver transplantation.
- Measurement of spontaneous and stimulated GH secretion, serum IGF-I and IGFBP-3 concentrations.
- Assessment of endogenous cortisol production and correlation with growth velocity.
Main Results:
- GH secretion was normal in most patients; serum IGF-I was normal, but IGFBP-3 was elevated in 62%.
- Endogenous cortisol production was reduced in most patients, particularly in the first year.
- Growth velocity positively correlated with basal and stimulated cortisol concentrations, but not with GH, IGF-I, IGFBP-3, or methylprednisolone dose.
Conclusions:
- Nocturnal GH secretion is generally sustained, with reduced response in few patients.
- Elevated IGFBP-3 is common, while IGF-I levels remain normal.
- Reduced endogenous cortisol production is prevalent and directly correlates with post-transplant growth velocity.
Abstract:
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.