This article is more than 5 years old. Information may no longer be current.

IGF-based growth hormone dosing improved growth response

Issue: April 2007

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

Insulin-like growth factor-based growth hormone dosing improved growth response in children of short stature, according to data from a recent study.

It also helped attain desired IGF-I levels, maintain serum IGF-I concentrations within desired target ranges, while avoiding IGF-I levels outside the normal range.

These data were published in the Journal of Clinical Endocrinology and Metabolism. Pinchas Cohen, MD, from the department of pediatric endocrinology at Mattel Children’s Hospital at UCLA, and colleagues tested whether IGF-I levels achieved during GH therapy are determinants of the growth-responses to GH treatment.

According to Cohen and colleagues, IGF-I-based GH dosing is clinically feasible. “Titrating the GH dose to achieve higher IGF-I targets results in improved growth responses, although at higher average GH doses,” they wrote.

IGF-I is thought to be the main mediator of GH actions on growth; therefore, the researchers postulated that a dosing algorithm based upon IGF-I response might better reflect the true GH requirement of a patient and allow for individualized care.

Study design

The researchers conducted an open-label, randomized and controlled trial.

All patients (n=172) were prepubertal (mean age, 7.53; mean height SD score, –2.64) and had low IGF-I levels (mean SD score, –3.56).

Participants “were randomized to receive one of two GH dose-titration arms in which GH dosage was titrated to achieve an IGF-I SD score at the mean (IGF_(low) group, n=70) or the upper limit of the normal range (+2 SD score, IGF_(high) group, n=68) or to a comparison group of conventional GH dose of 40 mcg/kg/day (n=34),” the researchers wrote.

After exclusions, 147 patients completed the trial; they had to have a height SD score less than –2, serum IGF-I SD score less than –1.0, a bone age <9 years for boy and <7 years for girls, and not have entered puberty within three months of the first visit, the researchers wrote.

All treatment groups started with 40 mcg/kg/day of rhGH (Norditropin, NovoNordisk) therapy. IGF-I target groups had a 20% dose change for each SD unit between actual and target IGF-I. These changes were based on the difference between measured and calculated IGF-I SD score (0 for IGF_(low) group and +2 for IGF_(high) group). All doses were adjusted at the first month visit and then every three months after that, until the end of the two-year study. In the conventional therapy group, the doses remained unchanged at 40 mcg/kg/day.

Greater height gains

“The IGF_(high) group demonstrated significantly greater height gains than the IGF_(low) and conventional groups with a height increase from a mean of –2.67 HT-SDS to –1.09 HT-SDS, and was approximately 0.5 SDS greater than in the other two groups,” they wrote. Patients in the IGF_(high) group gained nearly 4 cm more in height vs. the comparison groups after 24 months of treatment with GH, the data show.

Patients in the IGF_(high) group demonstrated the greatest increase in HT-SDS (1.58) compared with IGF_(low) (1.08) and conventional groups (1.00). There were no significant differences found between the latter two groups at any point in the study.

Target levels of IGF-I were achieved within six to nine months in the dose titration arms. Changes in HT-SDS were +1.0, +1.1 and +1.6 for conventional, IGF_(low) and IGF_(high) groups. However, patients in the IGF_(high) group demonstrated significantly greater linear-growth response compared with the IGF_(low) and conventional groups (P<.001).

Required doses were much higher in the IGF_(high) group vs. the other two groups; they were more than 2.5 times higher and ranged between 20 and 346 mcg/kg/day.

The researchers explained that annualized growth velocities achieved by IGF_(low), IGF_(high) and the conventional groups were 9.71, 11.20 and 9.01 cm/year at 12 months. At 24 months, they were 8.38 cm, 10.03 cm and 8.16 cm/year.

The mean daily doses for all three groups were 110 mcg/kg/day for the IGF_(high) group, 33 ug/kg/day for the IGF_(low) group and 41 mcg/kg/day for the conventional group. The researchers said there were no significant differences even though the IGF_(high) group received a substantially larger mean GH dose compared with the other groups.

The patients did experience adverse events, and the higher GH dose in the IGF_(high) group did not result in a lower safety profile compared with the other groups. “However, maintaining IGF-I levels within the normal range by adjusting GH dose might diminish the potential risks of excessive IGF-I levels during GH therapy, including the theoretical increase in long-term cancer risk,” the researchers wrote. – by Katie Kalvaitis

Dr. Cohen is a paid consultant for NovoNordisk.

For more information:

• Cohen P, Rogol AD, Howard CP, et al. IGF-based dosing of GH therapy in children: A randomized controlled study. J Clin Endocrin Metab. 2007.