IMPE Abstracts

Introduction: Measuring peak plasma cortisol after pharmacological stimulation induced by insulin tolerance test (ITT) and glucagon (GST) is often necessary to confirm or rule out the diagnosis of Central Adrenal Insufficiency (CAI). However, cortisol concentration cutoffs are still controversial, and these tests may result in adverse effects.

Objectives: In patients who underwent ITT and glucagon test, to evaluate: the correlation between the diagnostic tests evaluated (baseline cortisol, ITT, and glucagon), the agreement between the ITT test and glucagon, the diagnostic sensitivity and specificity of these tests, and the frequency of complications.

Materials and Methods: Retrospective longitudinal observational study including patients between zero and 18 years of age who underwent cortisol stimulation tests at a single tertiary center between 2001 and 2016. According to cortisol concentrations (F; mg/dL), baseline (Fbasal) and post-stimulus peak (Fpeak) patients were classified into three groups: IAC (Fbasal <5 and Fpeak <15), Indeterminate (Fbasal= 5 to 13 mg/dL and Fpeak=15-18) and Normal (Fbasal >13mg/dL and Fpeak >18). Cortisol was measured by RIA. We constructed ROC curves and evaluated the sensitivity (S), specificity (E) and likelihood ratios (LR) for Fbasal and Fpeak. We evaluated the correlation between Fbasal and Fpeak using the Kappa test. We constructed a conditional inference tree. The agreement between the ITT and Glucagon tests was evaluated by the Bland-Altman method. We evaluated the frequency of adverse events.

Results: 904 patients were evaluated (60.1% male; 10.1 years [0.1–17.7], height Z score= -2.5;-10 - 3.5]). IAC was confirmed in 107 patients (11.8%). There was a weak agreement between Fpeak and Fbasal (Kappa= 0.25;0.2-0.3). Fbasal (mg/dL) of 3.5 had S=99% and the best accuracy diagnosis (LR+=7.6). In GST, the AUC of the Fpeak was 0.62(0.41-0.63). Fpeak=12 presented the best diagnostic accuracy: LR+= 4.3. The conditional inference tree showed that solely, basal cortisol is not sufficient to diagnose patients with CAI. Fbasal and Fpeak were significantly lower in patients with ectopic neurohypophysis and interrupted stalk syndrome. The agreement between ITT and glucagon was adequate in most observed points, but still showed scattered values. During the ITT, 59.1% of the patients showed signs of hypoglycemia, and glucose supplementation was required in 18.6%. 12.2% of the patients had complications in GST, mostly nausea and vomiting.

Conclusions: Fbasal does not present good diagnostic accuracy. Cortisol stimulation tests are safe and necessary for most patients with suspected or possible IAC.