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Growth hormone secretion and circulating insulin-like growth factor-I (IGF-I) and IGF binding protein-3
A T Soliman1, N el Banna, I alSalmi
1Department of Pediatrics, Royal Hospital, Muscat, Oman.
Insights
Children with sickle cell disease (SCD) often have impaired growth due to abnormal growth hormone (GH) and insulin-like growth factor-I (IGF-I) axis function, suggesting IGF-I therapy may be more effective than GH therapy.
Area of Science:
- Pediatric Endocrinology
- Hematology
- Growth Hormone Axis Disorders
Background:
- Impaired growth (height and weight) is a common problem in children with sickle cell disease (SCD).
- The underlying mechanisms, particularly involving the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF binding protein-3 (IGFBP-3) axis, are not fully understood.
- GH resistance may contribute to growth deficits in children with SCD.
Purpose of the Study:
- To investigate abnormalities in the GH/IGF-I/IGFBP-3 axis in children with SCD.
- To determine if SCD is associated with GH resistance.
- To identify the etiological factors contributing to impaired growth in children with SCD.
Main Methods:
- Studied 21 children with SCD, assessing GH response to clonidine and glucagon provocation.
- Measured circulating concentrations of IGF-I and IGFBP-3.
- Utilized computed tomography (CT) scans to evaluate the hypothalamic-pituitary area.
- Administered a single injection of GH and measured IGF-I response, comparing with children with idiopathic short stature (ISS) and isolated GH deficiency (GHD).
Main Results:
- Nine of 21 children with SCD exhibited a defective GH response and had slower linear growth velocity, lower IGF-I and IGFBP-3 levels, and pituitary abnormalities (empty sellae).
- These findings suggest defective GH secretion and low IGF-I production are key factors in growth impairment in this subgroup.
- Children with SCD showed a blunted IGF-I response to GH administration compared to ISS and GHD controls, indicating partial GH resistance.
Conclusions:
- Defective GH secretion and decreased IGF-I production are significant contributors to impaired growth in some children with SCD.
- Partial GH resistance is present in short children with SCD.
- Therapeutic strategies targeting IGF-I may offer superior growth improvement compared to GH therapy in these patients.
Abstract:
Impaired growth involving both height and weight accompanying sickle cell disease (SCD) poses diagnostic and therapeutic problems. We undertook this study to test the hypothesis that this impaired growth is associated with abnormalities of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF binding protein-3 (IGFBP-3) axis in 21 children with SCD and that SCD is associated with GH resistance. Nine of 21 children with SCD had a defective GH response to both clonidine and glucagon provocation (peak < 10 micrograms/L); these children differed from the 12 others in having slower linear growth velocity (GV and GVSDS), lower circulating concentrations of IGF-I and IGFBP-3, and either partial or complete empty sellae in computed tomographic scans of the hypothalamic-pituitary area. In this group of patients with SCD, it appears that defective GH secretion and consequent low IGF-I production are the major etiological factors causing the slow growth. The two groups with SCD did not differ significantly in dietary intake, body mass index (BMI), midarm circumferences, skinfold thickness, serum albumin concentration, or intestinal absorption of D-xylose. A single injection of GH produced a smaller increase in circulating IGF-I in children with SCD with or without defective GH secretion versus 10 age-matched children with idiopathic short stature (ISS) and 11 children with isolated GH deficiency (GHD), suggesting partial GH resistance in the SCD group. The presence of defective GH secretion, decreased IGF-I synthesis, and partial resistance to GH in short children with SCD suggests that treatment with IGF-I may be superior to GH therapy for improving growth.