Depth and duration of hypoglycaemia achieved during the insulin tolerance test

Abstract

Context: The insulin tolerance test (ITT) is the gold standard for assessment of the pituitary adrenal axis but its use is limited because of concerns relating to the risk of hypoglycaemia. Objective: This study examined the depth and duration of hypoglycaemia achieved during the test in a large cohort of patients. Design: Two hundred and twenty ITTs were performed from 2005 to 2010. Setting: A 1200-bed University Teaching Hospital. Patients: Two hundred and twenty ITTs were carried out in patients with suspected or known pituitary disorders. Interventions: Intravenous insulin was administered to achieve nadir plasma glucose (NPG) of 2.2 mmol/l (39.6 mg/dl). Blood chemistry to show the cortisol and GH response to hypoglycaemic stress was measured. Main outcome measures: Predictors of depth and duration of hypoglycaemia, adverse events and within-subject variability of nadir glucose, peak cortisol and peak GH were studied. Results: Thirty percent of the cohort achieved a nadir glucose of !2.0 mmol/l (36 mg/dl) that lasted for 60 min or more. The NPG correlated positively with fasting plasma glucose (FPG; rZ0:56; P!0.0005), insulin dose (rZ0.27; P!0.0005) and weight (rZ0.21; P!0.004). The within subject variability of nadir glucose was 15.2%, peak cortisol was 11.7% and peak GH was 6.4%. The factors determining nadir blood glucose were FPG (bZ0.56, P!0.0005, 20% contribution) and weight (bZ0.14, P!0.05, 2% contribution). The five patients with adverse events had NPG and insulin dose comparable with the rest of the population. Conclusions: The hypoglycaemia achieved during the ITT is much lower than the target required. However, adverse events are few and do not relate to the depth of hypoglycaemia.

Factors associated with an inadequate hypoglycemia in the insulin tolerance test in Japanese patients with suspected or proven hypopituitarism

“…First, we evaluated other metabolic parameters such as blood pressure, lipid profile, hepatic function, and insulin resistance, which were not evaluated in previous studies. Second, we showed that HOMA-IR is useful as the novel predictor besides factors such as BMI, body weight, and/or FPG as shown in previous studies [4][5][6]. Third, in the present study, the method of statistical analysis is also different from that used in previ-…”

“…ITT, insulin-tolerance test; OR, odds ratio; 95% CI, 95% confidence interval; BMI, body mass index; SBP, systolic blood pressure; HbA1c, glycated hemoglobin; HOMA-IR, homeostasis model assessment of insulin resistance; TG, triglyceride; T-Cho, total cholesterol; HDL-Cho, high-density lipoprotein cholesterol; AST, aspartate aminotransferase; GH, growth hormone. ous studies [4][5][6]. Our statistical process may be interpreted as the ability to predict whether an inadequate or adequate hypoglycemia will occur in ITT.…”

“…In the literature to date, BMI or body weight, and/ or FPG are considered to be important factors affecting the adequacy of hypoglycemia during ITT in European and Australian patients with pituitary disease [4][5][6]. These results indicate that the factors affecting the severity of hypoglycemia during ITT are primarily related to metabolic factors, and not to anterior pituitary hormone levels.…”

“…Furthermore, ITT may increase the risk in patients with seizure disorders, cardiovascular disease, and cerebrovascular disease [1]. Some reports have shown that the degree of hypoglycemia is related to the adverse events of ITT [13,14], while others have reported that adverse events are infrequent and are not correlated with the severity of hypoglycemia [5,6,15]. Our study showed that both mild and serious adverse events are uncommon during ITT, when care is taken to exclude older patients and those with a history of ischemic heart disease or epilepsy.…”

“…It has been reported that body mass index (BMI) or body weight, and/or fasting blood glucose are important determinants of the dose of insulin required to achieve optimal degree of hypoglycemia in ITT in European and Australian patients with pituitary disease [4][5][6]. In addition, it is assumed that other metabolic parameters such as lipid profile, hepatic function, and insulin resistance could be associated with the efficacy/inefficacy of the stimulus in ITT.…”