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Pediatric Endocrine Unit Hospital de Clinicas Caracas Caracas-Venezuela
I read with interest the paper by Sas et al. (1) entitled "Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial."
The data of both Sas et al. (1) and de Zegher et al. (2) have shown how daily administration of recombinant human GH therapy in relatively large doses (up to 0.2 U/Kg · day in the study by Sas et al. and up to 100 µg/Kg/day in the report by the de Zegher et al.) accelerates growth significantly in short children born small for gestational age.
As stated by Sas et al. (1), initial data obtained by Tanner et al. (3) and Grunt et al. (4) in the early 1970s in GH-treated SGA children was disappointing, probably due to the low dose and frequency of GH administration. However, their statement that only recent short-term studies have demonstrated the effectiveness of GH therapy in this group of patients is inaccurate as both Foley et al. (5) in 1974 and Lanes et al. (6) in 1979 demonstrated that GH therapy accelerated the growth velocity in children with intrauterine growth retardation.
We (6) demonstrated that GH had a sustained positive effect on increasing the growth rates of these children, as 19 of our IUGR patients increased their growth velocity from 4.8 ± 1.4 cm/yr during the pretreatment period to 7.6 ± 2.3 cm/yr and 5.9 ± 1.4 cm/yr during 2 yr of therapy; their growth rates were significantly greater for both treatment periods than the pretreatment period, interval between, and posttreatment rates. At the onset of GH therapy our 19 patients were 4.5 ± 1.1 SD below the mean in height, and at the end of therapy they were 3.9 ± 1.6 SD, which was significantly closer to the mean (P < 0.05). In contrast, 19 untreated patients with IUGR were not significantly closer to the mean after 5 yr of follow-up. Our study also suggested that larger doses of GH were probably more effective in stimulating growth in patients with IUGR, as has been demonstrated by more recent studies published mainly in the 1990s.
A concern I have with the present use of relatively high GH doses in these children is the hyperinsulinemia noted in many of them. Sas et al. (1) found a significant increase in fasting insulin levels in both GH dosage groups, and, in addition, the area under the curve for insulin during OGTT was significantly higher after 1 yr of GH treatment when compared with baseline. Even though glucose levels and hemoglobin A1c concentrations remained within the normal range, the possible deleterious effects of long-term elevated insulin levels in these children need to be evaluated.
Footnotes
Address correspondence to: Roberto Lanes, M-209, P.O. Box O20010, Miami, Florida 33102.
Received October 11, 1999.
References
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