Growth Hormone Treatment for Down’s Syndrome?
ABSTRACT & COMMENTARY
Synopsis: Growth hormone treatment of infants with Down’s syndrome resulted in normal growth velocity but did not affect head circumference or mental or motor development. Growth velocity declined after treatment was stopped.
Source: Anneren G, et al. Growth hormone treatment in young children with Down’s syndrome: Effects on growth and psychomotor development. Arch Dis Child 1999;80:334-338.
Fifteen infants, 6-9 months of age with down’s syndrome, were treated with recombinant human growth hormone (HGH) for three years. Linear growth, psychomotor development, skeletal maturation, as well as serum concentrations of insulin-like growth factor (IGF-I), the binding protein for IGF-I (IGFBP-3), and cerebrospinal levels of IGF-II were measured sequentially. The mean height of the study group increased from -1.8 to -0.8 during HGH treatment, while a control group of Down’s syndrome infants fell from -1.7 to -2.2 over the same period. Head growth did not accelerate during treatment. There were no significant differences in mental or gross motor development in the treated group. Low serum concentrations of IGF-I and IGFBP-3 were found initially, and these became normal during HGH therapy.
Comment by Myron Genel, MD, FAAP
Down’s syndrome, the most common single specific cause of mental retardation, is also characterized by short stature, and reduced growth velocity is most pronounced between 6 months and 3 years of age. In normal infants, endogenous growth hormone has a major influence on growth beginning at about 6-9 months of age by stimulating the production of IGF-I. Therefore, the growth retardation characteristic of Down’s syndrome is most pronounced during the period when growth hormone normally starts to regulate growth.
The abundant availability of HGH produced by recombinant DNA techniques has prompted many studies of its use in a variety of disorders accompanied by short stature (including short, normal children) but without a well-defined disturbance of growth hormone production. Among the most prominent of these conditions is Down’s syndrome, perhaps because of its relatively high frequency, as well as the natural desire of families to explore every possible means to improve their status and development. This study from the Uppsala University Children’s Hospital in Sweden is notable because it was begun while the study patients were very young—6-9 months of age (average, 7.4 months)—and compared not only the changes in growth velocity but also head circumference and psychomotor development with a control group of Down’s syndrome subjects of a similar age.
While there was some improvement in growth velocity as well as increased elaboration of the growth hormone-dependent peptides IGF-I and IGFBP-3, the increased growth velocity was not sustained once treatment was discontinued. Most important, the small head circumference and the customary decline in psychomotor development characteristic of Down’s syndrome was no different in the treated children compared to the controls. It should be noted that the HGH dosage used in this study was 2-3 times larger than ordinarily used to treat children with proven growth hormone deficiency at this age. Anneren and colleagues properly conclude that they do not recommend or endorse HGH treatment of children with Down’s syndrome unless a deficiency of growth hormone can be established, and I would agree. Parenthetically, I should mention that the 15 children in the treatment arm of the study underwent four lumbar punctures each for measurement of IGF-II in cerebrospinal fluid. Although this was approved by the institutional ethics committee, I feel that such approval would not be forthcoming by most institutional review boards in the United States.
Treatment of infants with Down’s syndrome with recombinant HGH:
a. has no short-term effect on growth velocity.
b. significantly increases head circumference and psychological development.
c. may be effective if used in greater doses than that used in established growth hormone deficiency.
d. is not recommended unless a diagnosis of growth hormone deficiency can be established.
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