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Pediatric Endocrinology: New growth hormone dosing strategy boosts height in short children

12/01/2005

A recent UCLA study demonstrated significant growth improvement in children treated with growth hormone using a new dosing model compared to growth achieved using traditional dosing protocols. The new dosing method uses titration of the dose based on the growth hormone-dependent IGF-1 (insulin-like growth factor 1) to determine an individualized growth hormone dose calculated to achieve an IGF-1 level in the high-normal range for age and gender.

Researchers at UCLA’s Mattel Children’s Hospital randomized prepubescent children diagnosed with severe short stature to receive one of three types of growth-hormone therapies. One group was administered a conventional growth-hormone dose based on weight. Two other groups received doses that were periodically adjusted to achieve either an IGF-1 level equivalent to the mean for their age and gender, or at the upper limit of normal for IGF-1.

In this two-year study conduced at 25 sites across the nation, the team found that the group of children whose dosage was set to achieve a higher IGF-1 level gained 50 percent more height than children in the other two groups.

UCLA growth disorders program

The UCLA Growth Disorders Program can help children who are growing poorly achieve a more normal height. Children who are below the third percentile for height and those who are within the normal height range but are exhibiting decelerating growth should be referred for evaluation.

Program physicians take a careful medical history to try to identify possible genetic causes of short stature, pituitary disease or other factors that can interfere with growth. Thorough laboratory analysis helps physicians identify systemic disease markers and indicators of endocrine dysfunction. Physicians comprehensively evaluate the growth hormone IGF system using both static tests (including the GHdependent IGF-1 and IGFBP-3) and dynamic tests (such as the growth hormone stimulation test) and conduct a thorough radiological evaluation that includes a wrist x-ray to evaluate bone-age delay and to calculate predicted adult height. When necessary, an MRI of the pituitary gland can help determine if there is something interfering with growth hormone secretion.

The recommended treatment plan may include attending to an underlying non-endocrine condition that is causing poor growth, hormone treatments for thyroid disorders or treatment with either growth hormone or with the recently approved hormone IGF-1 in cases where growth hormone may not be effective. Growth hormone mediates growth by stimulating the production of IGF-1, which acts directly at the level of the bone to induce bone growth and growth improvement in general. When insufficient growth hormone causes a patient’s short stature, treatment with growth hormone is the best course. Some cases of short stature, however, are due to insensitivity to growth hormone; for these children treatment with IGF-1 bypasses growth hormone action and delivers the final product to induce growth.

Relevant publications

1. Lee K, Cohen P. Individualizing Growth Hormone Dosing in Children. Horm Res2001; 56:S29–34.
2. Cohen P, G Bright, AD Rogol, AM Kapplegaard, Rosenfeld RG. Dose response effects of hGH on auxological and biochemical parameters in GH deficient children. A randomized, three dose study in 110 children. JCEM2002; 87: 90-98.
3. Lee K-W, Cohen P. Individualized Growth Hormone Therapy in Children: Advances Beyond Weightbased Dosing. 2003 J Ped Endo Metab16:625-630.
4. Park P, Cohen P. The role of insulin-like growth factor I monitoring in growth hormone-treated children. Horm Res.2004; 62:S59-65.
5. Cohen P, Rogol AD, Howard CP, Bright GM, Anne-Marie Kapplegaard AM, Rosenfeld RG. IGFbased Dosing Optimizes the Efficacy of GH Therapy in Children with GHD and ISS: Results of a Randomized Concentration-Controlled Study. Presented in the Annual Meeting of the Endocrine Society 2005 and submitted for publication.
6. Park P, Cohen P. Insulin-like growth factor I (IGF-I) measurements in growth hormone (GH) therapy of idiopathic short stature (ISS). Growth Horm IGF Res.2005; 15:S13-20.

Contact information

Appointments for Pediatric Endocrinology and the Growth Disorders Clinic can be made by calling (310) 825-6244.





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