Abstract

To investigate whether a combination of the low-dose (1 μg) adrenocorticotropin (ACTH) stimulation test and glucagon stimulation test (GST) could overcome the problem of equivocal results with the GST or ACTH test alone in patients with pituitary disorders. The study included 41 adult patients with pituitary disorders and 20 healthy subjects who underwent evaluation of cortisol response to ACTH, GST, and a combination of both tests. Blood samples for cortisol measurement were obtained at baseline and 30, 60, 90, and 120 minutes after intravenous administration of ACTH 1 μg and 90, 120, 150, 180, 210, and 240 minutes after subcutaneous injection of glucagon 1 mg. The combination test was performed by injecting ACTH 1 μg at the 180-minute time point of the GST, with blood samples for cortisol measurement obtained at 210 and 240 minutes. Overall, 28 patients with normal cortisol response to both tests also had a normal cortisol response to the combination test. Ten patients with adrenal insufficiency in both tests also had adrenal insufficiency in the combination test, including a patient who had a peak cortisol value of 12.4 μg/dL (which is the cutoff value for the combination test). Two patients with adrenal insufficiency in the ACTH stimulation test and one patient with adrenal insufficiency in the GST had normal cortisol responses to the combination test. By using an appropriate cutoff value, the combination test may offer additional information in patients with equivocal results in the GST and ACTH stimulation test.

Highlights

  • The hypothalamic-pituitary-adrenal (HPA) axis should be evaluated appropriately in patients with pituitary disorders since the decision for glucocorticoid replacement therapy is based on the results of some tests, including the adrenocorticotropin (ACTH) stimulation test, insulin tolerance test (ITT), or glucagon stimulation test (GST) [1,2]

  • The first of its kind, we compared the combination of low-dose ACTH and GST (“combination test”) versus each test alone in the evaluation of the HPA axis in patients with pituitary disorders

  • The diagnosis of adrenal insufficiency has paramount importance in patients with pituitary disorders since this condition results in decreased quality of life and increased risk of adrenal crisis and mortality in stressful conditions

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Summary

Introduction

The hypothalamic-pituitary-adrenal (HPA) axis should be evaluated appropriately in patients with pituitary disorders since the decision for glucocorticoid replacement therapy is based on the results of some tests, including the adrenocorticotropin (ACTH) stimulation test, insulin tolerance test (ITT), or glucagon stimulation test (GST) [1,2]. The first of its kind, we compared the combination of low-dose ACTH and GST (“combination test”) versus each test alone in the evaluation of the HPA axis in patients with pituitary disorders. In the low-dose ACTH test, the lowest peak cortisol value in control subjects (14.6 μg/dL) was considered as the cutoff value for adrenal insufficiency.

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