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An Evaluation of Growth Hormone and IGF-1 Responses in Neonates with Hyperinsulinaemic Hypoglycaemia
Senthil Senniappan1, Khalid Hussain
1Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children, NHS Trust, WC1N 3JH, UK ; Developmental Endocrinology Research Group, Molecular Genetics Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Insights
Neonates with hyperinsulinaemic hypoglycaemia (HH) show a blunted cortisol response but an appropriate growth hormone (GH) counterregulatory response. Insulin-like Growth Factor 1 (IGF-1) and IGFBP3 levels are low during hypoglycaemia in these infants.
Area of Science:
- Neonatal Endocrinology
- Pediatric Metabolism
- Endocrinology Research
Background:
- Hyperinsulinaemic Hypoglycaemia (HH) is a common cause of severe neonatal hypoglycemia.
- Neonates with HH exhibit impaired cortisol counterregulation during hypoglycemia.
- The roles of growth hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) in HH are not fully understood.
Purpose of the Study:
- To compare serum GH, IGF-1, and IGFBP3 responses in neonates with HH during diagnostic fasting.
- To evaluate the counterregulatory hormonal responses in neonatal HH.
Main Methods:
- Retrospective data collection from term neonates diagnosed with HH.
- Exclusion of neonates with intrauterine growth retardation or on specific medical therapies.
- Analysis of serum GH, IGF-1, IGFBP3, cortisol, glucose, and insulin levels during diagnostic fasting.
Main Results:
- 31 neonates with HH were included (mean gestational age 38 weeks, mean birth weight 3.9 kg).
- During hypoglycemia (mean glucose 2.2 mmol/L), mean GH was 12.5 µg/L, IGF-1 was 29.2 ng/ml, and IGFBP3 was 1.21 mg/L.
- Mean cortisol levels were 201 nmol/L, indicating blunted counterregulation, while GH levels suggested an appropriate response.
Conclusions:
- Neonates with HH demonstrate relatively low IGF-1 and IGFBP3 levels during hypoglycemia.
- Serum GH levels indicate an appropriate counterregulatory response to hypoglycemia in HH.
- Cortisol counterregulatory hormonal responses are blunted in neonatal HH, necessitating further research into underlying mechanisms.
Abstract:
Background. Hyperinsulinaemic Hypoglycaemia (HH) is the most common cause of severe and persistent hypoglycemia in the neonatal period. It has been shown that the neonates with HH fail to generate adequate serum cortisol counterregulatory response to symptomatic hypoglycemia. However the role played by growth hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) is not clear. Objectives. To compare the serum GH, IGF-1, and IGFBP3 responses to HH in neonates undergoing diagnostic fasting studies. Population and Methods. Data was retrospectively collected on full-term neonates who presented with severe and persistent hypoglycemia and were confirmed to have HH. Neonates born with intrauterine growth retardation or those on medical therapy (diazoxide or octreotide) were excluded. Results. 31 neonates with HH (mean gestational age: 38 weeks and mean birth weight: 3.9 kg) were included in the study. The mean age at the time of diagnostic fast was 4 weeks, the mean glucose concentration during the fast was 2.2 mmol/L (SEM ± 0.09), and the mean insulin level was 11.9 mU/L (±2.12). The mean serum GH concentration during the hypoglycaemia was 12.5 µg/L (±1.53). The mean serum IGF-1 and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) levels were 29.2 ng/ml (±7.8) and 1.21 mg/L (±0.13), respectively. The mean cortisol concentration was 201 nmol/L (±33). Conclusions. Whilst the serum IGF-1 and IGFBP3 levels are relatively low during hypoglycaemia, the serum GH level does reflect an appropriate counterregulatory response to HH. The serum cortisol counterregulatory hormonal responses are blunted. Further studies are required to understand the mechanism(s) of these hormonal alterations in neonates with HH.
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