Low-dose glucose infusion after achieving critical hypoglycemia during insulin tolerance testing: effects on time of hypoglycemia, neuroendocrine stress response and patient's discomfort in a pilot study

Objective: The insulin tolerance test (ITT) is regarded as the gold standard for the evaluation of pituitary ACTH and growth hormone reserve. However, the intended critical hypoglycemia results in considerable discomfort and requires close surveillance during the test. Design and methods: In a pilot study, we evaluated whether the ITT could be markedly simplified, made less hazardous and more convenient by routine i.v. low-dose glucose administration after hypoglycemia has been achieved. Sixteen healthy subjects (three females, 13 males) were tested twice in a randomized, single-blinded fashion, receiving 0.15 IU insulin/kg body weight as an i.v. bolus. After hypoglycemia (serum glucose less than 2.2mmol/l) had been achieved, 500ml isotonic saline (protocol A (A)), or 500 ml 5% glucose solution (protocol B (B)) were infused over 30 min. Results: Compared with saline, glucose infusion shortened the period of hypoglycemia from 31 + 14 to 17 + 6 min (P < 0.01). In addition, prolonged duration of hypoglycemia (> 45 min) was reduced (6 subjects in protocol A vs none in protocol 13). Despite shorter duration of hypoglycemia, all subjects had adequate stimulated cortisol (> 500 nmol/l) and hGH (> 5 mu g/l) levels. Mean peak concentrations of plasma ACTH (24 +/- 12pmol/l (A) vs 21 +/- 8pmol/l (B)), serum cortisol (690 +/- 83nmol/l vs 634 +/- 83 nmol/l) and serum hGH (26 +/- 16 mu g/l vs 22 +/- 13 mu g/l) were slightly, but not significantly lower. In contrast, glucose infusion significantly reduced peak plasma epinephrine levels at 45 min (4.96 +/- 4.91 pmol/l (A) vs 1.53 +/- 1.1, pmol/l (B), P < 0.05) and ameliorated discomfort, as evaluated by a visual analog scale (P < 0.05). Conclusions: Taken together, our pilot study suggests that, while the duration of hypoglycemia is shortened and acute epinephrine response is reduced, low-dose infusion of glucose does not significantly alter peak cortisol and growth hormone responses during ITT. Studies with a larger number of subjects and patients with suspected hypopituitarism are needed to further evaluate this modified protocol.