Activity of GH/IGF-I axis in catabolic patients with sepsis or trauma

Abstract

Increased GH together with decreased IGF-I levels suggesting a peripheral GH insensitivity in critically ill patients have been reported by some but not by other authors. To clarify the activity of GH-IGF-I axis in catabolic states, basal and GHRH-stimulated GH secretion and IGF-I levels have been evaluated in patients with sepsis [SEP, n = 11; age (mean ± SEM) 56.1 ± 2.7 years] or trauma (TRA, n = 13; age 42.4 ± 4.1 years) on 1st, 3rd, 5th and 7th day after ICU admission, during artificial nutrition. SAPS II and MOF scores overlapped in both groups. Basal GH and IGF-I levels were also assayed in 24 normal subjects (NS, age 48.1 ± 4.3 years), 54 adult hypopituitaric patients with severe GH deficiency (GHD, age 44.8 ± 2.3 years), 19 patients with anorexia nervosa (AN, age 18.6 ± 0.6 years) and 12 patients with liver cirrhosis (LC, age 50.4 ± 2.8 years). In GHD, basal GH levels were lower than in NS (0.3 ± 0.1 versus 1.4 ± 0.2 μg/l, P < 0.01); similarly, IGF-I levels were markedly reduced and lower than in NS (68.6 ± 6.1 versus 213.5 ± 15.4 μg/l, P < 0.01). AN and LC basal GH levels were similar (10.0 ± 2.8 and 7.7 ± 2.1 μg/l) and higher than in NS (P < 0.01). AN and LC IGF-I levels were similar (70.4 ± 9.1 and 52.4 ± 10.5 μg/l), lower than in NS (P < 0.01) while overlapping with those in GHD. On the 1st day of ICU admission basal GH levels in SEP (0.7 ± 0.3 μg/l) and TRA (1.8 ± 0.6 μg/l) were similar to those in NS. IGF-I levels in SEP were lower than in TRA (82.9 ± 13.0 versus 127.0 ± 16.4 μg/l, P < 0.05) and both lower than in NS (P < 0.01). IGF-I levels in SEP were similar to those in GHD, AN and LC which were lower than in TRA (P < 0.01). GH levels in SEP and TRA remained similar up to the 7th day. In both groups the GH response to GHRH on the 3rd day was nearly abolished, clearly lower than in age-matched NS (GH peak, 2.5 ± 1.2 versus 10.5 ± 1.9 μg/l, P < 0.01). During parenteral nutrition, IGF-I levels increased both in SEP and TRA (P < 0.05 and P < 0.01, respectively). However, on the 7th day, IGF-I levels in SEP were clearly lower than in TRA (110.3 ± 9.5 versus 211.4 ± 25.5 μg/l, P < 0.01), overlapping the latter with those in NS. In conclusion, in severe catabolic conditions due to trauma and furthermore to sepsis, IGF-I levels are markedly low and similar to those in GHD. Somatotrope secretion is also impaired in both these catabolic conditions. Therefore, in patients with severe catabolism due to trauma or, particularly to sepsis, peripheral GH insensitivity and somatotrope insufficiency could both severely impair the activity of GH-IGF-I axis. Finally, artificial nutrition clearly increases IGF-I levels in post traumatic but not in septic catabolic states.