COMPARISON OF THE ACTH AND CORTISOL RESPONSES TO PROVOCATIVE TESTING WITH GLUCAGON AND INSULIN HYPOGLYCAEMIA IN NORMAL SUBJECTS

SUMMARY The glucagon stimulation test (GST) is often used to assess pituitary ACTH reserve, particularly when other tests are contra-indicated. In a preliminary investigation, in patients with pituitary disease, we failed to demonstrate the ACTH dependence of the cortisol response. We have therefore compared the ACTH, cortisol and glucose responses to glucagon (1 mg s. c.), insulin (0.2 U/kg i. v., ITT) and placebo in six healthy male volunteers, sampling every 10 min for 6 h. During the GST, mean |Mp SD serum cortisol rose from 256 ± 80 nmol/1 to a peak of 481 ± 164 nmol/1 (range 289–717 nmol/1, P < 0.01) in comparison with 280 ± 81 nmol/1 to 602 ± 110 nmol/1 (range 493-742 nmol/1) during the ITT (P < 0.002). The mean peak cortisol levels achieved in the two tests did not differ significantly. In the GST, plasma ACTH rose from a mean basal value of 10.9 ± 16.6 ng/1 to a mean peak level of 123 ± 76 ng/1 (P < 0.02) (ACTH ng/ 1 × 0.225 = pmol/1). The corresponding values in the ITT were 7.1 ± 16.2 ng/l and 263 ± 91 ng/1(P < 0.001). The mean peak ACTH level was significantly greater during the ITT (P < 0.05). Thus the cortisol response was ACTH dependent in both the GST and the ITT in normal subjects. Furthermore, the ACTH response was of sufficient duration to be detected by the usual procedure of sampling every 30 min. However, in clinical practice, more prolonged sampling should be undertaken during the GST, as two subjects showed their peak cortisol response after 3 h. In addition, this study suggests that the ‘normal’response to GST requires redefinition in view of four subjects in whom the peak cortisol response was less than 500 nmol/1.