Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children.

The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.

Comparison of self-reported and monitored compliance of daily injection of human growth hormone in burned children.

Objectives. We compared insulin-like growth factor (IGF-I) levels obtained in two groups with different methods of assessing compliance. Burned children were randomized to receive a daily injection of 0.05-0.1mg/kg per day of recombinant human growth hormone (rhGH) or placebo. Study design. One hundred twenty-five children (age range 6 months to 17 years) with total body surface area burns >40% participated in the study. Baseline levels of IGF-I were obtained at hospital discharge, at which time daily injections of rhGH or placebo were initiated. Assessment of IGF-I levels was repeated at 3-month intervals for 1 year. A directly monitored group met daily with research staff that witnessed the preparation and injection of the study drug. A self-reported group completed a Self Reported Compliance Questionnaire (SRCQ) that assessed compliance with drug regimen. A compliance of at least 85% (injections reported administered/maximal total injections possible) was accepted as being compliant. Data were analyzed using a one-way ANOVA followed by a Student Newman-Kuels test, with the results given as means+/-S.E.M. Results. The percent change in IGF-I levels between 6 and 9 months in the self-reported (22.7+/-7.9%) and monitored groups (21.9+/-8.6%) were similar. In contrast, the percent change in IGF-I levels in the placebo group was significantly decreased (-5.6+/-6.3%). Conclusions. Self-reported scores via an SRCQ is a potentially useful and valid method of assessing compliance of rhGH injections, as both reported and directly monitored methods yield similar changes in levels of IGF-I.

Effect of exogenous growth hormone and exercise on lean mass and muscle function in children with burns.

We tested the hypothesis that the administration of recombinant human growth hormone (rHGH) and exercise would increase lean body mass (LBM) and muscle strength in burned children to a greater extent than rHGH or exercise separately. Children, ages 7-17 yr, with >40% body surface area burned, were randomized into groups. One group (GHEX, n = 10) participated in a 12-wk in-hospital physical rehabilitation program supplemented with an exercise program and received 0.05 mg. kg(-1). day(-1) of rHGH. A second exercising group (SALEX, n = 13) received saline. A third group (GH, n = 10) received a similar dose of rHGH as GHEX and participated in a 12-wk, home-based physical rehabilitation program without exercise. The fourth group (Saline, n = 11) received saline and participated in a 12-wk, home-based physical rehabilitation program without exercise. The mean (+/-SE) percent change in lean body mass after 12 wk was not significantly different between GHEX (9.0 +/- 2.1%), SALEX (5.4 +/- 1.6%), and GH (5.8 +/- 1.8%) groups (P = 0.33). However, the mean percent change in muscle strength was significantly greater in the GHEX (36.2 +/- 5.4%) and SALEX (42.6 +/- 10.0%) groups than in the GH (-7.4 +/- 4.7%) or Saline (6.7 +/- 4.4%) groups (P = 0.008). In summary, rHGH GHEX, SALEX, and GH alone produced similar improvements in LBM. However, muscle strength was only increased via exercise.