High-dose growth hormone treatment of short children born small for gestational age.

Abstract

The effect of GH administration was evaluated over 2 yr in 50 short, prepubertal, non-GH deficient children born small for gestational age, who had been randomly allocated to a group receiving no treatment or daily sc GH treatment at a dose of 0.2 or 0.3 IU/kg. At the start of the study, mean age was 5.2 yr, bone age was 4.0 yr, height SDS was -3.5, height velocity SDS was -0.8, weight SDS was -2.7, and body mass index SDS was -1.9. Catch-up growth was observed in none of the untreated and all of the treated children. The response to GH treatment included a near doubling of growth velocity and of weight gain and a mean height increment of more than 2 SDS. GH treatment was associated with a distinct acceleration of bone maturation. The differences between the growth responses evoked by the two GH doses were minor. The prepubertal GH-induced catch-up growth was associated with elevated serum concentrations of insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and osteocalcin, whereas insulin-like growth factor-II levels remained unaltered. GH treatment was well tolerated. In conclusion, high-dose GH administration over 2 yr is emerging as a potential therapy to increase the short stature that results from insufficient catch-up growth in young children born small for gestational age. The long-term impact of this approach remains to be delineated.

The Somatotropic Axis in Short Children Born Small for Gestational Age: Relation to Insulin Resistance

“…It has been suggested that short SGA children may have a degree of IGF-I resistance as higher basal and GH-induced IGF-I levels are required to achieve a growth velocity similar to that of other children (40). Relative IGF-I resistance at the pituitary could contribute to the elevated GH secretion seen in our short SGA children, and would also be compatible with the observation that supra-physiologic GH doses are required to significantly improve final height prognosis in short SGA children (41)(42)(43). Thus, short SGA children may appear to have a shift in the set point of their GH/IGF-I axis.…”

“…Thus, children with GH deficiency or GH receptor deficiency tend to be obese (45,46). However, as in our study, short SGA children are often thin (17,19,41), suggesting that they remain sensitive to the metabolic effects of GH. The elevated pattern of GH secretion seen in our short SGA children is similar to that observed during fasting or malnutrition (47) and could lead to increased lipolysis and the development of insulin resistance.…”

Growth response to an individualized versus fixed dose GH treatment in short children born small for gestational age: the OPTIMA study

“…Current criteria and modalities for GH intervention in short children born small for gestational age (SGA) have been based on a series of clinical studies (1)(2)(3). The initial GH-induced catch up growth in these children has been shown to be influenced by age at start of therapy, weight, and height SDS and mid-parental height, as well as GH dose (4).…”

Growth Hormone Treatment in Children with Short Stature Born Small for Gestational Age: 5-Year Results of a Randomized, Double-Blind, Dose-Response Trial

“…Initial data were disappointing, probably due to the low dose and frequency of GH administration. Recent short term studies have shown that daily administration of recombinant human GH therapy in varying dosages accelerates growth significantly in short children born SGA (7,(15)(16)(17)(18)(19)(20)(21)(22).…”