The insulin hypoglycemia test: Hypoglycemic criteria and reproducibility

Nye, E.J., Grice, J.E., Hockings, G.I., Strakosch, C.R., Crosbie, G.V., Walters, M.M., Torpy, D.J. and Jackson, R.V. (2001) The insulin hypoglycemia test: Hypoglycemic criteria and reproducibility. Journal of Neuroendocrinology, 13 6: 524-530. doi:10.1046/j.1365-2826.2001.00664.x

Author Nye, E.J.
Grice, J.E.
Hockings, G.I.
Strakosch, C.R.
Crosbie, G.V.
Walters, M.M.
Torpy, D.J.
Jackson, R.V.
Title The insulin hypoglycemia test: Hypoglycemic criteria and reproducibility
Journal name Journal of Neuroendocrinology   Check publisher's open access policy
ISSN 0953-8194
Publication date 2001-06
Sub-type Article (original research)
DOI 10.1046/j.1365-2826.2001.00664.x
Volume 13
Issue 6
Start page 524
End page 530
Total pages 7
Place of publication Oxford, England
Publisher Blackwell Science Ltd
Collection year 2001
Language eng
Subject C1
321004 Endocrinology
730105 Endocrine organs and diseases (incl. diabetes)
Abstract The insulin hypoglycemia test (IHT) is widely regarded as the 'gold standard' for dynamic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to investigate the temporal relationship between a rapid decrease in plasma glucose and the corresponding rise in plasma adenocorticotropic hormone (ACTH), and to assess the reproducibility of hormone responses to hypoglycemia in normal humans. Ten normal subjects underwent IHTs, using an insulin dose of 0.15 U/kg. Of these, eight had a second IHT (IHT2) and three went on to a third test (IHT3). Plasma ACTH and cortisol were measured at 15-min intervals and, additionally, in four IHT2s and the three IHT3s, ACTH was measured at 2.5- or 5-min intervals. Mean glucose nadirs and mean ACTH and cortisol responses were not significantly different between IHT1, IHT2 and IHT3. Combined data from all 21 tests showed the magnitude of the cortisol responses, but not the ACTH responses, correlated significantly with the depth and duration of hypoglycemia. All subjects achieved glucose concentrations of of less than or equal to 1.6 mmol/l before any detectable rise in ACTH occurred. In the seven tests performed with frequent sampling, an ACTH rise never preceeded the glucose nadir, but occurred at the nadir, or up to 15 min after. On repeat testing, peak ACTH levels varied markedly within individuals, whereas peak cortisol levels were more reproducible (mean coefficient of variation 7%). In conclusion, hypoglycemia of less than or equal to 1.6 mmol/l was sufficient to cause stimulation of the HPA axis in all 21 IHTs conducted in normal subjects. Nonetheless; our data cannot reveal whether higher glucose nadirs would stimulate increased HPA axis activity in all subjects. Overall, the cortisol response to hypoglycemia is more reproducible than the ACTH response but, in an individual subject, the difference in peak cortisol between two IHTs may exceed 100 nmol/l.
Keyword Endocrinology & Metabolism
Pituitary-adrenal Axis
Corticotropin-releasing Factor
Cortisol Responses
Adrenocorticotropin Test
Arginine Vasopressin
Audiovisual Stimulus
Short Synacthen
Stress Tests
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 16 times in Scopus Article | Citations
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Created: Tue, 14 Aug 2007, 16:19:23 EST