Abstract

Background: Diagnosis of GH deficiency (GHD) and secondary adrenal insufficiency
entails evaluation by multiple dynamic stimulation tests in most cases. Insulin tolerance
test (ITT), the gold-standard test for evaluation of GHD and hypothalamo-pituitaryadrenal
(HPA) axis, carries risks and hence avoided in many institutes. Glucagon
stimulation test (GST) is a safe alternative to test for GHD and HPA axis.
Materials and Methods: We studied the diagnostic performance of GST compared to
ITT in adult patients with hypopituitarism and HPA axis suppression utility of
AACE/ACE proposed lower GH cut-point of 1 μg/L for adult GHD. GST and ITT were
performed on consecutive days as per standard protocol. Main outcome measures were
the GH and Cortisol response to GST and ITT. Hypopituitarism was due to Sheehan’s
syndrome in 13 patients, pituitary tumors in 4 subjects and empty sella syndrome in 1
patient. Two patients with HPA axis suppression due to exogenous glucocorticoids were
also evaluated with both GST and ITT.
Results: Sixteen patients had ≥3 pituitary hormone deficiencies. Peak cortisol levels
obtained during GST were significantly lower than the values obtained during ITT
(5.1±4.8 vs. 6.2±5.7 μg/dl; P = 0.004). Peak GH responses were not significantly different
between GST and ITT (0.4±0.7 vs 1.4±3.4 μg/L; P = 0.445). Using ITT as gold standard,
GH cut of 3 μg/L in GST had 100% sensitivity, 100% NPV, 89% PPV, and 90%
accuracy in diagnosing GHD. Adopting AACE/ACE proposed lower GH cut-point of 1
μg/L did not add further to the diagnostic accuracy of GST in GHD overall or in
overweight/obese subjects.
Conclusion: We conclude that GST can be reliably used in the evaluation of GHD as
well as HPA axis in hypopituitarism