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Study of growth hormone secretion and action in growth-retarded children with juvenile chronic arthritis (JCA)
A Tsatsoulis1, A Siamopoulou, C Petsoukis
1Endocrine Unit, Department of Medicine, Department of Paediatrics, University of Ioannina, Ioannina, Greece. atsatsou@cc.uoi.gr
Insights
Growth hormone (GH) secretion is normal in children with juvenile chronic arthritis (JCA), but their bodies show reduced response to GH action. This suggests GH insensitivity contributes to growth retardation in JCA patients.
Area of Science:
- Pediatric Endocrinology
- Rheumatology
- Growth Hormone Physiology
Background:
- Growth retardation is a concern in children with juvenile chronic arthritis (JCA).
- The underlying mechanisms, particularly concerning growth hormone (GH) action, require elucidation.
Purpose of the Study:
- To investigate stimulated and spontaneous GH secretion in growth-retarded children with active systemic JCA.
- To assess the response to GH action by evaluating Insulin-like Growth Factor-I (IGF-I) and IGF Binding Protein-3 (IGFBP-3) generation.
Main Methods:
- Assessed GH responses to insulin-induced hypoglycemia and clonidine stimulation in six JCA patients.
- Measured nocturnal pulsatile GH secretion via frequent blood sampling (20.00-08.00 h).
- Conducted an IGF-I generation test using biosynthetic human GH (hGH) in JCA patients and controls.
Main Results:
- JCA patients exhibited normal GH responses to stimulation tests and normal nocturnal GH pulse amplitude.
- IGF-I and IGFBP-3 levels were significantly lower in JCA patients compared to controls.
- JCA patients showed a blunted increase in IGF-I and IGFBP-3 following exogenous hGH administration compared to controls.
Conclusions:
- Stimulated and spontaneous GH secretion are normal in children with active systemic JCA.
- The impaired IGF-I and IGFBP-3 response to both endogenous and exogenous GH indicates GH insensitivity.
- GH insensitivity is a likely contributing factor to growth retardation in children with active systemic JCA.
Abstract:
The stimulated and spontaneous growth hormone (GH) secretion and the response to GH action were assessed in growth-retarded children with juvenile chronic arthritis (JCA), in order to determine the underlying mechanisms of growth retardation in such children. Six children (4 boys and 2 girls aged 10.7-13.8 years) with active JCA of systemic onset were included in the study which involved: (1) anthropometric measurements; (2) assessment of GH responses to insulin-induced hypoglycaemia and clonidine stimulation; (3) assessment of the nocturnal pulsatile GH secretion by measuring GH in blood samples obtained every 20 min from 20.00 to 08.00 h; and (4) the IGF-I generation test. As a control, the latter test was also performed in eight aged-matched children with physiological delay in puberty. Biosynthetic hGH (0.1 IU/kg BW) was administered s. c. for 4 days and blood samples were taken at baseline and the morning after the last GH injection for measurement of IGF-I and IGFBP-3. All six children with JCA were prepubertal and their growth velocity was <3 cm/year. The GH responses to both stimulation tests were normal (peak GH >20 mU/l). Analysis of the pulsatile GH secretion during the night revealed three-to-four GH pulses of normal amplitude (>20 mU/l). IGF-I (26.7+/-4.6 nmol/l, mean+/-SD) and IGFBP-3 (2.1+/-0.2 mg/l) levels were lower in the patients compared with the controls (43.0+/-3.7 nmol/l and 2.8+/-0.2 mg/l, respectively, P<0.01). Following stimulation with exogenous hGH, there was a significant increase in IGF-I and IGFBP-3 levels in the control group (85 and 73%, respectively), but only a small increase in the patients (31 and 14%). It appears that stimulated and spontaneous GH secretion is normal in children with active systemic JCA, but the response to endogenous and exogenous GH with regard to IGF-I and IGFBP-3 production is impaired, indicating a degree of GH insensitivity in such children.