Failure of anabolism in malnourished cancer patients receiving growth hormone: a clinical research center study.

Abstract

Previous work demonstrated that the provision of adequate or even excessive nutritional support is unable to reverse the negative nitrogen balance in many cancer patients. Our goal in a preliminary, short term study was to determine whether three daily GH injections (0.125 mg/kg.day, im) in cancer patients would increase insulin-like growth factor I concentrations and reverse the catabolic metabolic response to cancer, as indicated by reduced urinary nitrogen loss. Three days of GH therapy were associated with a significant increase in mean circulating GH (1.6 +/- 0.4 vs. 15.4 +/- 3.0 micrograms/L; P < 0.01), insulin-like growth factor I (112 +/- 15 vs. 329 +/- 54 micrograms/L; P < 0.01), insulin (57 +/- 11 vs. 184 +/- 46 pmol/L; P < 0.01), glucagon (63 +/- 11 vs. 77 +/- 11 ng/L; P < 0.05), and glucose (5.4 +/- 0.1 vs. 6.2 +/- 0.2 mmol/L; P < 0.05) concentrations. Twenty-four-hour urinary urea nitrogen (6.7 +/- 0.9 vs. 4.9 +/- 0.5 g; P < 0.05) and total nitrogen (7.8 +/- 1.2 vs. 6.0 +/- 1.2 g; P < 0.05) were significantly reduced. GH treatment in the group overall failed to alter leucine appearance (77.3 +/- 4.0 vs. 76.1 +/- 5.4 mumol/kg.h), leucine oxidation (11.8 +/- 1.5 vs. 9.6 +/- 1.0 mumol/kg.h), hepatic glucose production (13.5 +/- 0.8 vs. 14.2 +/- 0.8 mumol/kg.min), or estimated mean nitrogen balance (-0.24 +/- 0.97 vs. 0.85 +/- 0.75 g/day; t = 1.56; P = 0.10). Nitrogen balance was directly correlated with the percentage of the patient's ideal body weight (r = 0.776; P < 0.01). Seven of the 10 cancer patients were at or above 90% of ideal body weight, and they had a significant improvement in nitrogen balance (-1.46 +/- 0.99 vs. 0.60 +/- 1.03 g/day; P < 0.01). These patients also demonstrated a significant reduction in leucine oxidation (14.1 +/- 1.3 vs. 10.0 +/- 1.4 mumol/kg.h) and leucine appearance (81.2 +/- 3.8 vs. 72.9 +/- 3.3 mumol/kg.h; P < 0.05). This suggests that those most severely malnourished cancer patients may not respond anabolically to short term GH administration. We conclude that GH administration may be anabolic in cancer patients if there is not severe preexisting malnutrition.