Metabolic effects of growth hormone (GH) replacement in children and adolescents with severe isolated GH deficiency due to a GHRH receptor mutation.
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 5-17.5 years; three male) in a rural community in Northeast Brazil were treated with GHRT for 2 years and compared with indigenous normal controls.


METHODS
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.
Gleeson
Helena
H
Christie Hospital, Department of Endocrinology, Manchester, UK. helena@kgleeson99.freeserve.co.uk
Barreto
Elenilde S de A
ES
Salvatori
Roberto
R
Costa
Liana
L
Oliveira
Carla R P
CR
Pereira
Rossana M C
RM
Clayton
Peter
P
Aguiar-Oliveira
Manuel H
MH
D000293:Adolescent; D000704:Analysis of Variance; D001823:Body Composition / Q000187:drug effects; D016022:Case-Control Studies; D002648:Child; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D017353:Gene Deletion; D006442:Glycated Hemoglobin / Q000032:analysis; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D013006:Growth Hormone / Q000172:deficiency*; D006720:Homozygote; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009154:Mutation; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D013006:Growth Hormone; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D014280:Triglycerides; C048250:somatotropin releasing hormone receptor