The insulin tolerance test (ITT) is the gold standard investigation of suspected cortisol and/or growth hormone (GH) deficiency as hypoglycaemia is a potent stimulus for HPA and GH axis stimulation. We aim to review the sufficiency of current ITT protocols for achieving adequate hypoglycaemia, and their safety.
Consecutive ITTs performed over a 2-year period in 41 patients were retrospectively reviewed. Actrapid insulin was prescribed by known pituitary status (standard 0.1-0.15U/kg, 0.3U/kg acromegaly or Cushing’s disease, 0.07U/kg known HPA insufficiency). Additional insulin (half initial dose) was given if hypoglycaemia measured via bedside glucometer was not achieved after 45 minutes. Analysis included weight, insulin dose given (U/kg), BSL nadir, peak cortisol, peak GH and their timing. Cortisol deficiency was locally defined as peak cortisol ≤550nmol/L and GH deficiency as peak GH ≤10mU/L (severe ≤6mU/L) despite adequate provoked hypoglycaemia (≤2.2mmol/L).
35 patients (85%) achieved adequate hypoglycaemia (Group A). 6 patients (15%) who did not achieve adequate hypoglycaemia (Group B) had higher average weight (104±34 vs 80±17kg, p=0.01) and a trend to type 2 diabetes (33% vs 11%, p=0.21). Mean total insulin dose was similar between groups (0.11±0.02 vs 0.12±0.04U/kg). There was no serious adverse event. This is despite prolonged hypoglycaemia in 51% of Group A patients who achieved hypoglycaemia 5-45 minutes prior to BSL nadir. Detection rates of HPA axis and GH deficiency were high in our referral population (91% cortisol, 46% GH, 37% severe GH deficient in Group A patients).
Current ITT protocol insulin doses may be insufficient for achieving hypoglycaemia in patients who are obese, and possibly for those with type 2 diabetes. These subjects may require higher doses and larger studies are warranted. Conversely, in patients with adequate hypoglycaemia, hypoglycaemia can be prolonged and lower than the target required. Nonetheless the ITT is a well-tolerated test.