Metabolic Effects of GH Replacement in Children with Severe GH Deficiency
Metabolic Effects of GH Replacement in Children with Severe GH Deficiency
Background: The interpretation of the true effect of GH replacement therapy (GHRT) on metabolic status in GH deficiency (GHD) is often complicated by differing aetiologies of GHD and by the presence of additional hormone deficits.
Objective: To study the growth and response of the lipid profile and body composition to GHRT in a cohort of children with the same mutation in the GHRH receptor gene.
Design: Nine GH-deficient subjects (mean age 12·8 years, range 517·5 years; three male) in a rural community in Northeast Brazil were treated with GHRT for 2 years and compared with indigenous normal controls.
Main Outcome Measures: Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and body composition were measured at baseline and after 3, 12 and 24 months of GHRT.
Results: At baseline, the subjects with GHD had an adverse lipid profile, including elevated TC, elevated LDL-C and elevated TG. GHRT normalized TG in 3 months, LDL-C in 12 months and TC in 24 months. At baseline, older pubertal subjects with GHD had adverse body composition, including higher percentage fat mass (%FM), and GHRT induced a reduction in %FM that was maintained after 24 months. By contrast, younger prepubertal subjects did not have an adverse body composition.
Conclusions: Lipid profile was abnormal at baseline, while abnormal body composition was only seen in older subjects in late puberty, indicating that body composition is less sensitive to the effect of GHD than lipid profile. GHRT improves lipid profile at all ages, while it affects body composition only towards the end of growth, emphasizing its importance in achieving normal somatic development in the transition period.
The principal therapeutic goal of growth hormone replacement therapy (GHRT) in children with GH deficiency (GHD) is to promote linear growth. Studies in adults with GHD have emphasized the importance of GH in the regulation of protein, carbohydrate and lipid metabolism. Accordingly, GHD in adults is associated with reduced fat free mass (FFM) and increased fat mass (FM) and disorders of lipid metabolism. Studies of GHRT in adults have shown an improvement in body composition (by reducing FM and increasing FFM). The effect on lipid profile is less consistent, although the majority have demonstrated an improvement (reviewed in). More recently, interest has turned to the metabolic consequences of discontinuing GHRT at cessation of growth in adolescents with GHD. Abnormal body composition (predominantly reduced FFM) has been observed at the end of growth in GH-deficient subjects treated with GHRT during childhood. Most, but not all, studies have indicated that continuation of GHRT can help in achieving normal adult body composition, by continuing to increase levels of FFM and reduce FM, and maintaining improved lipid profile. Consequently, paediatric endocrinologists have been encouraged to look beyond growth and to consider the metabolic effects of GHD and their amelioration with GHRT.
The studies assessing the effect of GHRT on lipid profile in children with GHD have reported conflicting results. One explanation could be the wide variety of causes of GHD, with differences in severity and duration of GHD, and the variable presence of other hormone deficits. In addition, the assessment of body composition in children with GHD is more complex than in adults because of the marked changes throughout puberty. Appropriate analysis requires robust normal control data from the same population. This has not been the case for the majority of studies of body composition in childhood.
The study of a cohort of children and adolescents from members of a homogeneous extended kindred with severe congenital isolated GHD from a single gene mutation in the GHRH receptor (GHRH-R) gene offers an invaluable opportunity to clarify the response of body composition and lipid profile to GHRT.
Background: The interpretation of the true effect of GH replacement therapy (GHRT) on metabolic status in GH deficiency (GHD) is often complicated by differing aetiologies of GHD and by the presence of additional hormone deficits.
Objective: To study the growth and response of the lipid profile and body composition to GHRT in a cohort of children with the same mutation in the GHRH receptor gene.
Design: Nine GH-deficient subjects (mean age 12·8 years, range 517·5 years; three male) in a rural community in Northeast Brazil were treated with GHRT for 2 years and compared with indigenous normal controls.
Main Outcome Measures: Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and body composition were measured at baseline and after 3, 12 and 24 months of GHRT.
Results: At baseline, the subjects with GHD had an adverse lipid profile, including elevated TC, elevated LDL-C and elevated TG. GHRT normalized TG in 3 months, LDL-C in 12 months and TC in 24 months. At baseline, older pubertal subjects with GHD had adverse body composition, including higher percentage fat mass (%FM), and GHRT induced a reduction in %FM that was maintained after 24 months. By contrast, younger prepubertal subjects did not have an adverse body composition.
Conclusions: Lipid profile was abnormal at baseline, while abnormal body composition was only seen in older subjects in late puberty, indicating that body composition is less sensitive to the effect of GHD than lipid profile. GHRT improves lipid profile at all ages, while it affects body composition only towards the end of growth, emphasizing its importance in achieving normal somatic development in the transition period.
The principal therapeutic goal of growth hormone replacement therapy (GHRT) in children with GH deficiency (GHD) is to promote linear growth. Studies in adults with GHD have emphasized the importance of GH in the regulation of protein, carbohydrate and lipid metabolism. Accordingly, GHD in adults is associated with reduced fat free mass (FFM) and increased fat mass (FM) and disorders of lipid metabolism. Studies of GHRT in adults have shown an improvement in body composition (by reducing FM and increasing FFM). The effect on lipid profile is less consistent, although the majority have demonstrated an improvement (reviewed in). More recently, interest has turned to the metabolic consequences of discontinuing GHRT at cessation of growth in adolescents with GHD. Abnormal body composition (predominantly reduced FFM) has been observed at the end of growth in GH-deficient subjects treated with GHRT during childhood. Most, but not all, studies have indicated that continuation of GHRT can help in achieving normal adult body composition, by continuing to increase levels of FFM and reduce FM, and maintaining improved lipid profile. Consequently, paediatric endocrinologists have been encouraged to look beyond growth and to consider the metabolic effects of GHD and their amelioration with GHRT.
The studies assessing the effect of GHRT on lipid profile in children with GHD have reported conflicting results. One explanation could be the wide variety of causes of GHD, with differences in severity and duration of GHD, and the variable presence of other hormone deficits. In addition, the assessment of body composition in children with GHD is more complex than in adults because of the marked changes throughout puberty. Appropriate analysis requires robust normal control data from the same population. This has not been the case for the majority of studies of body composition in childhood.
The study of a cohort of children and adolescents from members of a homogeneous extended kindred with severe congenital isolated GHD from a single gene mutation in the GHRH receptor (GHRH-R) gene offers an invaluable opportunity to clarify the response of body composition and lipid profile to GHRT.
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