some authors propose to conduct consistently two additional tests for differential diagnosis (DD) of NDH with the main purpose to confirm or exclude the autonomous hyperinsulinemia (AH; insulinoma): determination the capillary beta-hydroxybutyrate (BHB) during prolonged fasting test (FT), and glucagon test (GT) at the moment of hypoglycemia. GT is more labor-intensive, high-cost and lead to potential complications. Therefore, we assumed that the BHB determination alone is enough for NDH DD.
To compare the efficiency of GT and BHB determination in AH diagnosis.
In 59 patients aged 44 (23, 74) years with suspected NDH we conducted FT (was interrupted if glycaemia ≤ 2.8 mmol/l with symptoms of neuroglycopenia or, if maintaining normoglycemia, after 72 h). At the end of FT BHB was determined, then GT was conducted: 1 mg of glucagon was administrated iv with venous blood sampling for glucose through 3, 5, 10, 15, 20, 30 min. BHB ≤ 2.7 mmol/l and increase in glycemia ≥ 1.4 mmol/l during GT confirmed AH, opposite results indicated hypoinsulinemia.
63% (n = 37) of patients had hyperinsulinemia (group 1); 37% (n = 22) hypoinsulinemia/not confirmed NDH (group 2). BHB was 0.2 [0.1; 0.3] mmol/l in group 1; 4.4 [2.3; 4.9] mmol/l in group 2, P < 0.001. Sensitivity, specificity, accuracy of method were: 97.3%, 72.7%, 88.1%, accordingly. ROC-analysis indicated the excellent quality of model: AUC 0.989 [0.967; 1.000]. All patients with false positive results (1.85 [1.60; 2.00] mmol/l; n = 6) had insulin resistance (HOMA-IR > 2.7), that likely blocked ketogenesis. False negative result (3.3 mmol/l) identified in one patient with exacerbation of pyelonephritis, associated with increased ketogenesis. Increase in glycemia after glucagon administration was 2.8 [2.0; 3.4] mmol/l in group 1; 0.8 [0.6; 1.1] mmol/l in group 2, P < 0.001. Sensitivity, specificity, accuracy of method were: 94.6%, 100%, 96.6%, accordingly. ROC-analysis indicated the excellent quality of model: AUC 0.974 [0.937; 1.000]. False negative results (1.03 and 0.68 mmol/l; n = 2), presumably, were due to the influence of any other hormones on the glucagon effect on liver. Results of BHB determination and GT were identical in 90% of cases.
BHB determination and GT are highly sensitive and highly specific methods DD of NDH at the laboratory stage, with a small advantage for GT. But GT is more labor-intensive, high-cost and lead to potential complications. We assume that BHB determination during FT (especially at the end) is mandatory; GT should be used in doubtful cases as an additional method.
Russian Science Foundation (project 17-75-30035).
22 May 2021 - 26 May 2021