Prospective comparison of the glucagon stimulation test (GST) with the insulin tolerance test (ITT) in patients following pituitary surgery

Objective: The ITT is the gold-standard for assessment of GH and ACTH reserve but has certain contraindications. GH and cortisol responses of <3ng/ml and <500nmol/l, respectively, have been defined as evidence of deficiency. The GST like the ITT stimulates both the ACTH and GH secretion and is suggested to be a good alternative in terms of efficiacy. However, there are limited prospective data with modern assays on sensitivity and specificity for the GST in comparison to the ITT. Aim of this study was an evaluation of the diagnostic utility of the GST in patients with hypothalamo-hypopituitary disease following pituitary surgery. Design and patients: ITT (0–120') and GST (0–240') were performed within 7 days in 49 patients (26 men, age 28–64) at least 3 months after transsphenoidal surgery. Serum GH and cortisol were measured by Immulite 2000 assay (Siemens AG). ROC analysis was performed to identify thresholds for GST with at least 95% sensitivity.

Results: By ITT, 18/49 cases were classified as cortisol insufficient. For cortisol insufficiency in GST, ROC analysis revealed a cut-off of 599 nmol/l with 100% sensitivity and 32% specificity. In addition, ROC analysis revealed a lower cut-off of 277 nmol/l with >95% sensitivity and 72% specificity for cortisol sufficiency. Using both upper and lower cut-off, 25/49 (51%) of subjects could not be diagnosed by GST alone and required further testing. Regarding GHD, 21/49 cases were classified as insufficient by ITT. ROC analysis revealed a cut-off of 2.5ng/ml with 95% sensitivity and 79% specificity. 7/49 (14%) cases were discordant in terms of defining GHD when comparing GST and ITT results, with 6 subjects being treated for GHD according to GST although being sufficient in ITT. Further analysis revealed, that the GST could be limited to 3h sampling period without any loss in accuracy.

Conclusion: In our prospective series of patients with pituitary disease, GST is a potential alternative test for assessment of GH reserve, but poor for ACTH reserve, as demonstrated by comparison with the ITT. Test-specific cut-offs should be applied to avoid misinterpretation.