A Cross-Sectional Study to Evaluate the Safety and Efficacy of the Insulin Tolerance Test

Introduction: The insulin tolerance test (ITT) is the current standard for the diagnosis of pituitary diseases such as growth hormone deficiencies (GHD). Previous reports indicated that the ITT as having a high adverse event profile, and the cosyntropin test as being sensitive enough to diagnose GHD in adults. The purpose of this study is to validate the safety and efficacy of the ITT. Design: Over 400 ITT tests were conducted over the course of 3 years from (2017-2020) at our facility. This study is only focused on adult physiology (Cohort Age 16 - 78) and excludes any pediatric tests. An important measure, time spent in critical state (Tc), is done to know the expected time a patient is to remain hypoglycemic, both for patient expectations and clinician logistics. We did not use a CGM, instead drew blood samples on set intervals for glucose measurements. Since the measurements aren’t continuous, a consistent overestimation is done for all subject encounters to capture the maximum time spent in hypoglycemia. Insulin like growth factor one (IGF-1) was measured before the test was conducted and is listed in the spreadsheet. Growth hormone peaks were and the time to reach that peak (Tp) were also measured. This time is calculated from the listed time of the first dosage of insulin to the time of the GH peak. Other measures listed in the spreadsheet include a brief medical history of the patient, their age, weight, gender, and the blood pressure and heart rate measured at test completion. Any immediate interventions such as intravenous fluid injections were listed. Symptoms of hypoglycemia are excluded as a complication of the test. This is due to the inherent nature of the ITT whose goal is to drop one’s blood sugar past normal ranges. Results: Our results show (0.45%) rate of adverse events. 2 patients in the entire cohort suffered from seizures during their hypoglycemic period. Both of them were successfully aborted with Ativan, and patients were monitored until recovery from post ictal state and discharged home with stable vitals and no acute symptoms. It was later discovered these patients had remote history of epilepsy and should’ve been excluded from this trial. Of the remaining 448 subject encounters, (20%) of them required urgent intervention to BP. Zero of those patients suffered any other symptoms or ongoing adverse effects. 5 patients underwent the ITT twice, again, with no adverse effects. Conclusion: No permanent adverse events or hospitalizations were reported. Based on our findings the clinical safety concerns of the ITT test are minimal compared with the benefit of obtaining an accurate diagnosis in this patient cohort, if done within the correct protocol. Using IGF-1 measures as a determinant of GHD is wildly inaccurate as seen in our results. Combining IGF-1 with the Cosyntropin test is not a good enough measure for diagnosing GHD. The ITT test remains the most accurate and reliable test available today.