Informing the Discussion on rhGH for Idiopathic Short Stature

Informing the Discussion on rhGH for Idiopathic Short Stature 150 150 Juan F. Sotos, MD

Growth hormone treatment for children with idiopathic short stature has remained controversial. Based on my experience and that of others, I recommend treatment.

The use of growth hormone for idiopathic short stature has remained controversial in the field of endocrinology, mainly because of previous reports of its modest benefit and high cost. These reports led to the impression that growth hormone-treated children with idiopathic short stature remain short as adults, on the lower level of the normal range, with an improvement in adult height after years of treatment in the order of 4 cm — a modest benefit that is outweighed by the high cost of the treatment.

Many of the studies in the past, however, used growth hormone doses of 0.16 to 0.26 mg/kg/week, which may not have been adequate. Furthermore, some of the studies included children with intrauterine growth retardation or with familial short stature, which may have affected the results. The benefit obtained seems dose-dependent; a mean benefit of 7.5 to 8 cm was reported in a few studies with higher doses of 0.32 to 0.4 mg/kg/week. In our recent publication on growth hormone for children with idiopathic short stature, the dose ranged from 0.3 to 0.4 mg/kg/week.

Our experience with growth hormone treatment of children with idiopathic short stature for more than 20 years at Nationwide Children’s Hospital was a positive one, with the normalization of the height and growth during childhood and adolescence and the attainment of normal adult heights from the 1st percentile to the 80thpercentile for males and females. The adult height benefit over untreated controls was 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm (6.7 to 10.5 cm) for females, a significant improvement.

Furthermore, the treatment was safe — there were no significant adverse effects. The IGF-1 levels remained essentially within the ranges expected for different stages of puberty, and they were also normal after treatment. These findings are relevant to the concerns of possible future side effects because of the mitogenic effects of IGF-1.

All the parents and the children in our study who attained adult heights were pleased with the results, happy to be normal in height and grateful for the treatment. The most consistent parental perception of the treatment’s benefit was the improvement of self-esteem in their children, who they said felt happy to be normal and not different. Other benefits perceived were cessation of teasing, bullying and psychological stress. As a consequence of the aforementioned alone, I would recommend treatment.

The increased benefit from an increase in the dose is similar to results obtained in some other health conditions. The dose of growth hormone of 0.3 mg/kg/week was shown to be of higher benefit for children with growth hormone deficiency than the dose of 0.15 mg/kg/week used previously. Dosages of 0.37 mg/kg/week in patients with Turner syndrome and up to 0.45 mg/kg/week in patients small for gestational age were found to be more effective than lower dosages previously used.

Other reasons for the modest benefit of treatment reported in the past could be because many of the children included in the studies were affected with familial short stature. Our study and two previous studies have shown that final adult height and total height gain of children with familial short stature were significantly lower than of children with non-familial short stature. Thus, the inclusion of an unknown number of children with familial short stature in the cohorts (treated or control) in previous studies could have affected the results.

One of the main problems that has been often addressed in the past is the significant cost of growth hormone, which limits the availability to children who may need it and raises questions about the use of health resources. The high cost of biopharmaceuticals is a problem concerning public health services. Cost influences pediatric endocrinologists in their decisions to treat and third party payers (private insurance groups or health agencies, state or national) in their decision to support treatment. A number of families cannot afford the copays. The pharmaceutical industry should address the problem of cost. If the price were reasonable, it would be the right thing to do to help these children attain an adult height within the range judged to be normal by national health standards and by society.

For all of the reasons mentioned above, I believe it is appropriate to treat idiopathic short stature with doses of growth hormone that will be effective in helping children attain a normal adult height.



Sotos JF, Tokar NJ. Growth hormone significantly increases the adult height of children with idiopathic short stature: comparison of subgroups and benefit. International Journal of Pediatric Endocrinology. 2014, 2014(1):15.

About the author

Juan F. Sotos, MD, has been a practicing pediatric endocrinologist for over 50 years.He will be retiring in 2015 after many significant contributions to the field, including the characterization of Sotos Syndrome.