The role of growth hormone in determining birth size and early postnatal growth, using congenital growth hormone deficiency (GHD) as a model.
OBJECTIVE
The role of GH in early human growth is unclear. Congenital GH deficiency (CGHD) provides a useful tool to explore this putative role. We have assessed the effects of CGHD on birth size and early postnatal growth, and the further impact of the presence of additional pituitary hormone deficiencies and midline brain defects on these parameters.


METHODS
Weight, length and BMI expressed as standard deviation scores (SDS), over the first two years of life, were retrospectively compared in 44 GH-deficient children (M:F 26 : 18). Thirty-eight of 44 patients underwent GH provocation testing and all patients had neuro-imaging of the brain. The patients were divided into three groups of increasing phenotypic complexity {group A [n = 12, isolated GHD, no midline defects], group B [n = 10, combined pituitary hormone deficiency (CPHD); no midline defects], group C (n = 22, CPHD with midline defects)}.


RESULTS
Mean birth weight, length and BMI SDS were -0.4, -0.9 and +0.1 SDS, respectively. The differences were significant for weight (P = 0.03) and BMI (P = 0.003), but not length (P = 0.3) SDS, between groups A and C. Of the three groups, group A had a lower weight and BMI SDS than group C. The prevalence of postnatal complications (n = 25) was significantly different in the three groups [group A (8%), group B (80%), group C (73%); P < 0.001] and particularly between patients with isolated GH deficiency (IGHD) (group A) and CPHD (groups B and C; P < 0.0001). No patients in group A presented with neonatal hypoglycaemia as compared with 70% of those in group B and 59% in group C (P = 0.001). A reduced length SDS was observed in all patients within 6 months of birth and the reduction was greatest in group B (P = 0.03). Group C remained significantly (P < 0.05) heavier at 12, 18 and 24 months compared to group A. BMI SDS was significantly (P < 0.05) greater at all study points in CPHD patients (groups B and C) as compared with IGHD. Serum GH concentrations at testing did not correlate significantly with birth length (r = -0.08, P = 0.7), birth weight (r = -0.08, P = 0.6) or the age at induction of GH treatment (r = 0.12, P = 0.5). There were no significant differences between peak serum GH concentrations in patients in groups A (7.8 +/- 6.3 mU/l), B (3.9 +/- 4.8 mU/l) or C (8.7 +/- 5.4 mU/l).


CONCLUSIONS
Length, weight and BMI data from our study groups suggest that GH per se has a minimal effect on intrauterine growth but a significant effect during the infancy period. Early growth may also be influenced by the complexity of the hypopituitary phenotype reflected by the presence of additional pituitary hormone deficiencies and midline forebrain defects.
Mehta
Ameeta
A
London Centre for Paediatric Endocrinology and Metabolism, Institute of Child Health, University College London, London, UK.
Hindmarsh
Peter C
PC
Stanhope
Richard G
RG
Turton
James P G
JP
Cole
Tim J
TJ
Preece
Michael A
MA
Dattani
Mehul T
MT
D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D001724:Birth Weight / Q000502:physiology; D001827:Body Height / Q000502:physiology; D049628:Body Size / Q000502:physiology*; D001921:Brain / Q000002:abnormalities; D002657:Child Development / Q000502:physiology*; D036861:Delivery, Obstetric; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008954:Models, Biological; D009154:Mutation; D010907:Pituitary Hormones / Q000172:deficiency; D012189:Retrospective Studies; D013972:Thyrotropin / Q000172:deficiency
D010907:Pituitary Hormones; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin