L‐Arginine and insulin‐tolerance tests in the diagnosis of adult growth hormone deficiency: influence of confounding factors

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Abstract
In the attempt to define a GH stimulation test with high specificity and reproductibility, few studies have addressed the influence of potential interfering external factors on the test result. We therefore tested the influence of physical activity (admission to hospital on test morning) and mild heat exposure on the GH response to l-arginine stimulation test (Arg) and insulin-tolerance test (ITT). One Arg stimulation test and one ITT were performed in all subjects during standard conditions (overnight hospital stay, 10 hours fasting). In addition, each subject was randomized to undergo either two additional Arg tests, or two ITTs, performed under two different conditions: admission to hospital on the morning of the test and during standard conditions except for heat exposure before testing. The four tests were performed in random order. Twenty-two patients (six women, 16 men) (mean age ± SEM, 38.3 ± 5.3 years and 36.1 ± 2.7 years, respectively) presenting with pituitary disease and a group of healthy age and gender-matched normal subjects (six women, 13 men) (age 38.3 ± 4.8 years and 35.7 ± 2.4 years, respectively) participated. During the GH-stimulation tests serum GH, cortisol, blood glucose, and plasma glucagon were measured and compared in the three different test conditions. During standard conditions, peak GH response was higher in the ITT compared to the Arg test in the control group (23.4 ± 3.6 mU/l vs 11.6 ± 2.0 mU/l, P = 0.004), and the specificity of the ITT was higher (18/19 versus 13/19, P = 0.047). Minor heat exposure before the ITT (temperature rise 0.24 ± 0.05°C, range 0.0–0.5°C) did not change the GH response in the healthy adults whereas admission to hospital on the morning of the test reduced the GH response significantly (P < 0.05). The lowest blood glucose did not change in the three situations and did not correlate with peak GH during the ITT. In the patients there were no significant differences between the GH response during different conditions. Plasma glucagon did not significantly differ between the different test conditions in the control group (P = 0.88), but there was a significant decrease in the glucagon response to the test performed after hospital admission on the test morning in the patients (P < 0.025). Serum cortisol response in the control group did not differ in the three situations. Since provocative GH responses are influenced by external factors, conditions should be standardized to optimize the reproductibility and specificity of the tests. Furthermore the higher specificity of the insulin-tolerance test as compared to the arginine stimulation test was confirmed.

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