SAT-452 - Evaluation of Adrenal Insufficiency in Patients After Non-Functioning Pituitary Adenoma Using Lispro Insulin Tolerance Test and Glucagon Stimulation: A Safety and Efficacy Study

Introduction: Secondary adrenal insufficiency (SAI) is a complication with high morbidity in the postoperative period of pituitary tumors. The insulin tolerance test (ITT) is the gold standard for evaluating the hypothalamic-pituitary-adrenal (HPA) axis, but its risks, such as severe hypoglycemia, and possible discomfort during its performance, are a significant limitation. The glucagon stimulation test (GST) emerges as a safer alternative with fewer adverse effects. Additionally, the shortage of regular insulin in Brazil has motivated the search for validation of rapid-acting analogs, such as insulin lispro, in the ITT.

Objective: To compare the safety and efficacy of the ITT with insulin lispro versus the GST in evaluating cortisol reserve in patients in the postoperative period of non-functioning pituitary adenomas, analyzing the diagnostic agreement between the tests under multiple cut-off points.
Methodology: A prospective, observational study with 6 patients who underwent both tests with a minimum interval of one week. Intravenous lispro insulin was used in the ITT. Intramuscular glucagon was used in the GST. The cortisol response was assessed at multiple cut-off points (ITT: Cortisol >11 μg/dL, Cortisol >14 μg/dL, Cortisol >15 μg/dL, Cortisol >18 μg/dL; GST: Cortisol >8.8 μg/dL) and agreement was analyzed using Cohen's Kappa coefficient.

Results: The safety profile was superior in the GST, with no significant side effects, while 83.3% of patients reported multiple adverse effects in the ITT. For all analyses, a significance level of 5% (p < 0.05) was adopted. The concordance analysis for the diagnosis of adrenal insufficiency showed variable results depending on the ITT cut-off point. For cutoffs of >11 μg/dL and >14 μg/dL, agreement with the GST was excellent (Kappa = 1.000). For cutoffs of >15 μg/dL and >18 μg/dL, agreement was moderate (Kappa = 0.571), with 1 discordant case. Analysis of capillary versus plasma glucose showed significant overestimation of capillary values during ITT-induced hypoglycemia (p < 0.001).

Conclusion: The GST proved to be a significantly safer and better tolerated test than the ITT. Diagnostic agreement for cortisol reserve assessment is promising, especially with lower cutoff points in the ITT, but the existence of disagreements in more stringent criteria, coupled with the low number of cases, requires caution. The use of lispro insulin in the ITT was effective and validated in this cohort. GST represents a valuable alternative, but its interchangeability with ITT depends on the standardization of cut-off points and validation in larger studies.

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