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Abnormal growth hormone secretory dynamics in children with familial hypercholesterolemia
1Developmental Endocrinology Branch, National Institute of Child Health Human Development, Bethesda, Md.
Insights
Children with LDL receptor pathway defects show altered growth hormone and somatomedin C levels. Mevinolin treatment did not impact these growth factors, indicating no significant effect on growth in these patients.
Area of Science:
- Pediatric Endocrinology
- Metabolic Disorders
- Pharmacology
Background:
- Children with low-density lipoprotein (LDL) receptor pathway defects exhibit altered growth patterns.
- Understanding growth hormone (GH) secretory dynamics and somatomedin C (SM-C) is crucial for assessing growth in these patients.
Purpose of the Study:
- To assess GH secretory dynamics and plasma SM-C concentrations in prepubertal patients with LDL receptor pathway defects.
- To evaluate the effect of mevinolin, an HMG-CoA reductase inhibitor, on GH and SM-C levels and growth velocity.
Main Methods:
- Studied four prepubertal patients with LDL receptor pathway defects before and after 2 months of mevinolin treatment.
- Measured 24-hour GH levels, GH pulse amplitude, plasma SM-C concentrations, and growth velocity.
- Assessed GH provocative testing response.
Main Results:
- Pre- and posttreatment GH levels and pulse amplitude were similar and higher than controls.
- Pre- and posttreatment SM-C levels were similar and lower than controls.
- Mevinolin treatment did not significantly alter GH, SM-C, or growth velocity.
Conclusions:
- Children with LDL receptor pathway defects have GH and SM-C abnormalities similar to other chronic diseases.
- Mevinolin treatment does not appear to affect these biochemical abnormalities or long-term growth.
- Close monitoring of growth rate and skeletal maturation is recommended for these children.
Abstract:
Growth hormone secretory dynamics and plasma somatomedin C concentrations were assessed in four prepubertal patients with defects in the low-density lipoprotein (LDL) receptor pathway before and after 2 months of treatment with mevinolin, an HMG-CoA reductase inhibitor that reduces intracellular cholesterol. Pre- and posttreatment mean 24-hour growth hormone levels and pulse amplitude were similar and tended to be higher than in age-matched prepubertal controls. Pre- and posttreatment somatomedin C levels were also similar and lower than in age-matched prepubertal controls. All patients responded to growth hormone provocative testing with a peak response of greater than 7 ng/ml, independent of treatment status. Growth velocity was not significantly altered in any patient following 2 months of treatment with mevinolin, and was within the normal range for age. Thus, children with defects in the LDL receptor pathway express abnormalities in growth hormone secretion and somatomedin C generation comparable to those seen in other chronic diseases. Treatment with mevinolin has no apparent effect on these biochemical abnormalities, suggesting that it may not have long-term effects on growth. Regardless of mevinolin therapy, children with defects in the LDL receptor pathway may manifest a degree of growth retardation and, hence, growth rate and skeletal maturation should be closely monitored.