SAN DIEGO — Short children grew far taller when their growth hormone doses were adjusted according to their insulin-like growth factor 1 levels rather than to their weight, according to randomized study results.
“IGF-1 levels do matter,” said Pinchas Cohen, M.D., professor and director of research and training in the division of endocrinology at the University of California, Los Angeles, School of Medicine.
The notion of targeting dosing in order to maximize height in children of short stature is somewhat new and had been thought clinically impractical, Dr. Cohen said at a clinical symposium during the annual meeting of the Endocrine Society.
However, it was “possible and doable” to adjust doses according to a simple IGF-1-based algorithm. This approach resulted in “significant, quite dramatic improvement in height” for some children enrolled in the 2-year, multicenter trial.
In all, 172 children diagnosed with growth hormone deficiency or idiopathic short stature were enrolled in the trial sponsored by Novo Nordisk Inc., a manufacturer of human growth hormone, and the Lucile Packard Foundation for Children's Health.
The children were aged 3–15 years and significantly below normal height for their age, with a mean standard deviation score of -2.63. They also had low levels of IGF-1, the core mediator of growth hormone action on linear growth.
The complex study design featured a control group of 34 children who received a conventional 40 mcg/kg per day dose of growth hormone. Two other groups received targeted, adjustable doses of growth hormone based on IGF-1 levels at 3-month checkups.
One group received growth hormone in amounts necessary to achieve normal IGF-1 levels, and included 70 children. The other group, which numbered 68 children, received enough growth hormone to drive their IGF-1 levels two standard deviations above the norm.
The three groups achieved mean IGF-1 levels of +0.4, +0.4, and +2.0 standard deviation scores in the first 9 months of the study, and doses of 41 mcg/kg per day, 33 mcg/kg per day, and 110 mcg/kg per day were required to sustain these levels, said Dr. Cohen.
Only a small, nonsignificant difference was seen in children receiving standard growth hormone doses according to weight and those receiving doses targeted at a normal IGF-1.
The big difference in height was seen in children who received growth hormone at a dose aimed at raising their IGF-1 levels to two standard deviations greater than the norm. In this group, children with growth hormone deficiency grew 45% more, and children with idiopathic short stature grew 58% more than children in the other groups.
Side effects and adverse events were similar in all three groups.
Interestingly, a huge variability was seen in the amount of growth hormone required to maintain targeted IGF-1 levels among individual patients: 9–114 mcg/kg per day in the first targeted group and 20–346 mcg/kg per day in the second.
Dr. Cohen serves as a consultant or advisory board member or receives research support from a number of companies that manufacture human growth hormone, including Genentech Inc., Pfizer Inc., Eli Lilly & Co., Novo Nordisk Inc., and Serono Inc.