BACKGROUND: The glucagon test (GT) is a promising alternative to the insulin hypoglycemia test (IHT) in diagnosis of secondary adrenal insufficiency (SAI). AIM: To study the feasibility of using the GT in patients after craniospinal irradiation and to determine the cut-off value to rule out SAI. METHODS: A total of 28 patients (14 males and 14 females) with the median age of 19 years (17; 23) who had undergone combination treatment (surgery, craniospinal irradiation (35 Gy) with boost to the tumor bed, and polychemotherapy) of extrapituitary brain tumors no later than 2 years before study initiation and 10 healthy volunteers of matching sex and age were examined. All the subjects underwent the GT and IHT with an interval of at least 57 days. The cortisol, ACTH, and glucose levels were measured. RESULTS: Twelve out of 28 patients were diagnosed with SAI according to the IHT results. ROC analysis revealed that cortisol release during the GT 499 nmol/L ruled out SAI [100% sensitivity (Se); 62% specificity (Sp)], while the absence of a rise 340 nmol/l verified SAI (Sp 100%; 55% Se). For GT, the area under a curve (AUC) was 93.6%, which corresponds to a very good diagnostic informativity. In 19 patients, the IHT and GT results were concordant (in ten patients, the release of cortisol occurred above the cut-off value in both tests; no release was detected in nine patients). In nine cases, the results were discordant: the maximum cortisol level detected in the GT was 500 nmol/l, but the IHT results ruled out SAI (the GT yielded a false positive outcome). Contrariwise, in three (10.7%) patients the release of cortisol detected in the GT was adequate, while being insufficient in the IHT test. Adverse events (nausea) were reported during the GT test in 9 (25%) subjects; one patient had hypoglycemia (1.8 mmol/l). CONCLUSION: GT is highly informative and can be used as a first-level stimulation test for ruling out SAI in patients exposed to craniospinal irradiation performed to manage brain tumors. The cortisol level of 500 nmol/L is the best cut-off value for ruling out SAI according to the GT results. The insulin hypoglycemia test is used as the second-level supporting test in patients with positive GT results.

Endocrine disorders are common in patients after treatment for brain tumors in childhood. Growth hormone (GH) deficiency is the most common consequence of cranial irradiation. Objective — to evaluate the prevalence of GH deficieny and metabolic disorders in patients after treatment for malignant tumors of the posterior cranial fossa (MT PCF) in childhood. Material and methods. In this study 40 patients (21 men, 19 women) who had undergone treatment for MT PCF were assessed. Patients underwent surgery, chemotherapy and craniospinal irradiation (CSI) in a dose of 34.9±1.6 Gy with a boost to the PCF 51.3±9.2 Gy. Age at the time of the survey — 19.8±3.05 years; age at the time of treatment — 10.9±3.4 years; follow-up — 7.2±4.2 years. Patient’s anthropometric and laboratory parameters were measured, GH failure was diagnosed by two tests – insulin tolerance test (ITT) and glucagon stimulation test (GST). Results. According to ITT GH deficiency was observed in 82.1% and according to GST in 60.0% of patients. When comparing two tests GST showed 100% specificity, but lower sensitivity (72.2%). Manifestation of GH deficiency depends on the age at the time of treatment (p=0.002). There is significant correlation between age at the time of treatment and SDS of final height (r=0.632; p<0.001). We found a significant correlation between age at the time of treatment and BMI (r=–0,327; p=0.04). Dyslipidemia occurred in 50% of cases. Insulin resistance was recorded in 16.7% of patients. We found significant correlation between the HOMA-IR and BMI (r=0.336; p=0.034). Conclusions. In patients after treatment for MT PCF in childhood GH deficiency and metabolic disorders is highly prevalent. This group of patients should be monitored by endocrinologist for timely detection and treatment of GH deficiency and metabolic complications.