Metabolic status of children with growth hormone insensitivity syndrome and responses to treatment with IGF-I.
Studies to date on the treatment with insulin-like growth factor I (IGF-I) of children with growth hormone (GH) insensitivity syndrome (GHIS) have concentrated principally on the effects of IGF-I therapy on the GH-IGF-I axis and on growth velocity. Little is known, however, about the metabolic status of children with GHIS and the consequences of IGF-I treatment on circulating intermediary metabolites involved in glucose homeostasis. We have studied 5 children with GHIS, aged 4.5-9 years, 3 male and 2 female, before and after 3 months of treatment with recombinant IGF-I, 80 microg/kg s.c. twice a day. The children were short (height SDS -3.8 to -7.3) and growing slowly (height velocity 1.8-3.4 cm/year). All were neurodevelopmentally normal at the time of the study with no history of severe symptomatic hypoglycaemia, in particular during the neonatal period. Before treatment, 4 of the 5 children demonstrated spontaneous hypoglycaemia (blood glucose <2.6 mmol/l), particularly at night, accompanied by substantial hyperketonaemia (range 1.43-4. 63 mmol/l) and hyperfattyacidaemia (range 1.11-3.08 mmol/l). After 3 months of IGF-I treatment, the blood glucose concentrations in the diurnal profile were increased, with improvement in spontaneous hypoglycaemia and with increased fasting tolerance. The postprandial insulin-to-glucose ratio was reduced. GHIS is thus associated with asymptomatic nocturnal hypoglycaemia without apparent neurological deficit. Despite functional GH deficiency, brisk counter-regulation to hypoglycaemia occurred as evidenced by hyperfattyacidaemia and hyperketonaemia. Treatment with IGF-I twice a day improved fasting glucose tolerance, diurnal blood glucose concentrations, and postprandial insulin-to-glucose ratios. There was no exacerbation of hypoglycaemia on treatment. We suggest that in severe GH resistance, a protective mechanism exists for the brain from the effects of hypoglycaemia, at least partially mediated by excessive production of counter-regulatory metabolic fuels.
Brain
C E
CE
London Centre for Paediatric Endocrinology and Metabolism at Great Ormond Street Hospital for Children and Institute of Child Health, London, UK.
Hubbard
M
M
Preece
M A
MA
Savage
M O
MO
Aynsley-Green
A
A
D001786:Blood Glucose / Q000378:metabolism; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D004700:Endocrine System Diseases / Q000188:drug therapy* / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005990:Glycerol / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use*; D007657:Ketone Bodies / Q000097:blood; D008297:Male; D011994:Recombinant Proteins; D013577:Syndrome
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005990:Glycerol