Abstract
Objective The insulin tolerance test (ITT) is the gold standard endocrine test used to assess the integrity of the growth hormone (GH) and cortisol axes. The ITT has potential risks, and severe hypoglycaemia may necessitate intravenous glucose rescue. There is no clear consensus as to the optimal insulin dose for the ITT. Therefore, we sought to compare the standard dose (0.15 U/kg) and a low-dose ITT (0.1 U/kg). Design Single-centre audit of ITT data (2012–2021). Patients and Measurements. Patients who underwent an ITT to assess possible GH deficiency/adrenal insufficiency were included. Glucose, GH, and cortisol were measured at baseline and 30, 45, 60, 90, and 120 minutes following I.V. insulin bolus (0.15 U/kg or 0.10 U/kg). Results Of the ITTs performed, only 3/177 (1.7%) did not achieve adequate hypoglycaemia (≤2.2 mmol/L) with a single insulin dose. In total, 174 patients (43.5 ± 12.1 yrs, mean ± standard deviation) were included for analysis (0.15 U/kg: n = 113, 0.10 U/kg: n = 61). All 174 subjects had adequate hypoglycaemia regardless of baseline fasting blood glucose level or insulin dose. Neither nadir glucose nor glucose delta (i.e., baseline minus nadir) differed between insulin doses. Trends in both cortisol and GH responses over time were similar between groups, and a greater proportion of patients receiving the standard dose had an adequate cortisol response (77/106 (72.6%) vs. 32/60 (53.3%), p=0.01). The rates of glucose rescue did not differ in a subset of 79 patients, with on-demand glucose rescue in 4/35 (11%) for the standard dose and 2/44 (5%) for the low dose (p=0.25). Conclusions Our results suggest that the low-dose ITT produces comparable glucose, cortisol, and GH responses to the higher dose. Given the risks associated with hypoglycaemia, the low dose appears to be preferable to the standard dose ITT in most circumstances.
Highlights
Seminal work in the 1960s led the widespread acknowledgement of the insulin tolerance test (ITT) as the gold standard for assessing adrenal insufficiency and growth hormone deficiency [1,2,3]
The ITT is a provocative endocrine test whereby intravenous (I.V.) insulin induces hypoglycaemia and the ensuing cortisol and growth hormone (GH) response is used to evaluate the integrity of the hypothalamo-pituitary-adrenal (HPA) and GH axes, respectively. e degree of hypoglycaemia (i.e., target blood glucose (BG) ≤2.2 mmol/L) largely determines the magnitude of the hormonal responses and test sensitivity. e ITT has sufficient sensitivity and specificity to establish the diagnosis of GHD [4]
With adequate hypoglycaemia, the ITT may be preferred over other test procedures as it can assess both GH responsivity and HPA axis integrity, which is vital when considering the necessity for corticosteroid replacement therapy as well as GH replacement [5]
Summary
Seminal work in the 1960s led the widespread acknowledgement of the insulin tolerance test (ITT) as the gold standard for assessing adrenal insufficiency and growth hormone deficiency [1,2,3]. The ITT is a provocative endocrine test whereby intravenous (I.V.) insulin induces hypoglycaemia and the ensuing cortisol and growth hormone (GH) response is used to evaluate the integrity of the hypothalamo-pituitary-adrenal (HPA) and GH axes, respectively. E ITT necessitates continuous BG monitoring as well as ongoing assessment of autonomic (e.g., anxiety, sweating, tachycardia) and neurologic responses (e.g., hunger, tingling, blurred vision, faintness, problems with cognition) [12] that may warrant I.V. glucose administration to correct severe hypoglycaemia As such, it is a potentially risky, labour intensive, time-consuming, and expensive (in terms of personnel) test to perform. Rates of patients meeting cortisol and GH thresholds (>450 nmol/L, >3 μg/L, respectively) and requiring on-demand glucose rescue were compared using the χ2 test. All statistical analyses were performed using R (version 4.0.3) [18] and multilevel models were estimated using the lme R package [19]
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