Endogenous anabolic hormones and hypermetabolism: effect of trauma and gender differences

Abstract

Objective: Protein degradation, negative nitrogen balance and compromised structure of essential organs have been associated with resistance and decreased production of anabolic hormones. In turn, increased levels of anabolic hormones are associated with improved survival. The aims of the present study were to determine the pattern of anabolic hormones, resting energy expenditure and cytokines in severely thermally injured pediatric patients and to compare these parameters in female and male patients.

Methods: Sixty-five children (1 to 16 years of age) sustaining a severe thermal injury (> or =40% TBSA) were included into the study. Patients were further divided into females (n = 22) and males (n = 43). Patient demographics, nutritional support, incidence of sepsis, inhalation injury, and mortality were noted. Resting energy expenditure was measured during hospital course by indirect calorimetry. Blood was drawn 0, 10, 20, and 40 days postburn and serum insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 and -3 (IGFBP-1, and -3), growth hormone, insulin, and cytokines were measured.

Results: There were no significant differences between females and males for demographics, nutritional intake, or concomitant injuries. In both groups, endogenous anabolic agents were drastically decreased by 3- to 5-fold up to 40 days posttrauma. Females had significantly higher levels of IGF-I, IGFBP-3, growth hormone, and insulin when compared with males, P < 0.05. Increased levels of anabolic hormones were associated with decreased stay on the ICU (females 36 +/- 22 days versus males 53+/- 39 days), decreased serum IL-1beta and TNF-alpha as well as resting energy expenditure, P < 0.05.

Conclusion: Data indicate that despite adequate nutritional support, severe thermal injury leads to decreased anabolic hormones over a prolonged period of time. Female patients had significantly increased levels of anabolic hormones, which are associated with decreased proinflammatory mediators and hypermetabolism, leading to a significant shorter ICU stay compared with male patients.

FIGURE 1. A, Serum IGF-I levels dropped 3- to 4-fold immediately after burn. Forty days after trauma, IGF-I levels were still significantly decreased compared with normal values. Normal values for unburned, normal age-matched children: IGF-I: 365 ± 15 μg/mL. B, Serum IGFBP-3 was decreased 4-fold compared with normal. Forty days postburn, levels did not reach normal concentrations. Normal levels: IGFBP-3: 2.8 ± 0.9 μg/mL. C, Serum IGFBP-1 was increased by 2-fold during the first 10 days postburn. At 20 days after trauma, levels decreased and reached normal values. Normal levels: IGFBP-1 115 ± 15 μg/mL. D, Serum insulin was decreased immediately after burn. Insulin increased almost 2-fold over the study period. Normal levels: 20 ± 5 IU/mL. E, Serum GH was 4- to 5-fold decreased after the burn trauma. Serum GH demonstrated no recovery over the 40-day study period and remained decreased. Normal levels: GH 8 ± 1 μg/mL.

FIGURE 2. Predicted energy expenditure was increased during acute hospitalization and at discharge by 130%. Predicted REE decreased towards normal levels 6 months after burn but was still elevated, at 120% predicted from normal.

FIGURE 3. A–C, Serum IL-1β (A) was significantly increased compared with normal levels over the 40-day study period. Normal serum IL-1β: 0.1–0.8 pg/mL. B, Serum Il-6 was also increased but decreased towards normal levels at 40 days postburn. Normal IL-6: 0–5 pg/mL. C, Similarly, serum TNF-α was increased immediately after burn but decreased to approach normal levels 40 days after injury. Normal serum TNF-α: 0–2 pg/mL.

FIGURE 4. A, In females and males, serum IGF-I levels dropped immediately after burn. Ten and 40 days after trauma, IGF-I levels were significantly increased in female patients when compared with males. *Significant differences between females versus males, P < 0.05. Normal values for unburned, normal, age-matched children: IGF-I: 365 ± 15 μg/mL. B, Serum IGFBP-3 decreased immediately in both groups. In accordance with IGF-I levels, IGFBP-3 levels were significantly increased in female patients compared with males. *Significant differences between females versus males, P < 0.05. Normal levels: IGFBP-3: 2.8 ± 0.9 μg/mL. C, Serum IGFBP-1 was found significantly increased 10 days postburn in female patients compared with males. *Significant differences between females versus males, P < 0.05. Normal levels: IGFBP-1 115 ± 15 μg/mL. D, Serum insulin was in the normal range in both groups in the early phase postburn, but then increased. Female patients had significantly higher insulin levels compared with males 40 days postburn. *Significant differences between females versus males, P < 0.05. Normal levels: 20 ± 5 IU/mL. E, Serum GH decreased in male patients over the 40-day study period. GH was increased in female patients and significantly greater 40 days postburn. *Significant differences between females versus males, P < 0.05. Normal levels: GH 8 ± 1 μg/mL.

FIGURE 5. Predicted REE was significantly increased in males during acute hospital stay, at discharge, and at 6 months after burn when compared with females, P < 0.05 (Fig. 5). Females returned to baseline at 6 months after burn, whereas males remained elevated, at 120% predicted REE. *Significant differences between females versus males, P < 0.05.

FIGURE 6. A, Serum TNF-α was significantly decreased female patients 40 days after injury compared with males, P < 0.05. Normal serum TNF-α: 0–2 pg/mL. B, Interleukin-1β was decreased in females on days 10 and 20 after burn when compared with males, P < 0.05. Normal serum IL-1β: 0.1–0.8pg/mL. *Significant differences between females versus males, P< 0.05.