Cortisol cut-points for the glucagon stimulation test in the evaluation of hypothalamic pituitary adrenal axis

Abstract

Diagnosis of adrenal insufficiency requires evaluation by dynamic stimulation tests. The insulin tolerance test (ITT) is accepted as the gold-standard test for the evaluation of hypothalamo-pituitary-adrenal (HPA) axis but the test is unpleasant and dangerous. Although it takes more time, glucagon stimulation test (GST) is a good alternative to ITT. The primary aim of this study was to compare the ITT and GSTs in the evaluation of HPA axe in patients with pituitary disorders. We conducted a prospective study in which ITT and GST were performed within 7 days in 81 patients. Serum cortisol was measured. We divided our population in Group 1 (G1): Adrenal Insufficiency (Peak cortisol under ITT <200 ng/mL) and Group 2 (G2): normal response (Peak cortisol under ITT >200 ng/mL). Receiver-operating characteristic (ROC) analysis was performed to identify the thresholds for GST. The mean peak of cortisol under GST was not significantly different from that obtained after ITT in the whole cohort (182.67 ± 89.07 ng/mL vs. 179.75 ± 79.01 ng/mL), and it was significantly reduced in patients of G1 (p < 10). ROC curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cut-off to GST of 167 ng/mL (sensitivity, 89%; specificity, 79%). Using this cut-off, 86.4% of the patients were correctly classified. In our prospective series, GST is a potential accurate and safe alternative test for the assessment HPA. Test-specific cut-offs should be applied to avoid misinterpretation.

Secondary Adrenal Insufficiency After COVID-19 Diagnosed by Insulin Tolerance Test and Corticotropin-Releasing Hormone Test

“…Our patient was diagnosed as having secondary AI on the basis of inadequate cortisol and ACTH secretion responses on the ITT and the CRH test. The ITT is a gold standard test to assess the integrity of the entire HPA axis, and the GST can also be used for the same purpose [16], although they are not useful for distinguishing between secondary and tertiary AI. In our case, an addition of the CRH test successfully differentiated secondary AI from CAI, which is the first time this has been done.…”

Long‐term corticosteroid use, adrenal insufficiency and the need for steroid‐sparing treatment in adult severe asthma

“…However, insulin‐induced hypoglycaemia should only be performed in a specialist endocrine unit and is contraindicated in patients with known or suspected seizures, arrhythmias or ischaemic heart disease. Other specialist tests, including glucagon stimulation, are also best performed in conjunction with endocrinology [ 50 ]. Collection of plasma for ACTH measurement (to help distinguish primary [raised ACTH and low cortisol] from secondary [low/inappropriately normal ACTH and low cortisol] AI) requires specific sample handling and should be discussed with the endocrine laboratory.…”

Secondary Adrenal Insufficiency: New Aspects of Diagnosis and Therapy

“…Уровень кортизола > 599 нмоль/л исключает НН, тогда как более низкие показатели не позволяют подтвердить диагноз (у 10-20% здоровых лиц кортизол на фоне пробы не достигает 599 нмоль/л) [2]. В связи с этим некоторые авторы предлагают другой диагностический уровень -460 нмоль/л (167 нг/мл), при котором тест обладает чувствительностью 89% и специфичностью 79% [28].…”