Abnormal growth hormone secretory dynamics in children with familial hypercholesterolemia

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 wihin 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.