This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Erturk, E. Articles by Barkan, A. L. Search for Related Content PubMed PubMed Citation Articles by Erturk, E. Articles by Barkan, A. L.

Evaluation of the Integrity of the Hypothalamic-Pituitary-Adrenal Axis by Insulin Hypoglycemia Test¹

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: Ariel L. Barkan, M.D., Division of Endocrinology and Metabolism, 3920 Taubman, Box 0354, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0354.

We retrospectively reviewed dynamic ACTH and cortisol responses to insulin hypoglycemia in 193 subjects with suspected ACTH deficiency to ascertain the predictive values of various diagnostic criteria. Based on the achievement of a peak cortisol level of 18 µg/dL or above, 133 subjects were classified as having an intact hypothalamic-pituitary-adrenal (HPA) axis, and 60 subjects were determined to have ACTH deficiency. Baseline and peak cortisol concentrations were strongly correlated (r = 0.63; P < 0.0001). Peak cortisol increased in parallel to ACTH increments, but plateaued at approximately 22 µg/dL at peak ACTH levels above approximately 75 pg/mL (r = 0.61; P < 0.0001). Basal cortisol values above 17 µg/dL or below 4 µg/dL were highly predictive of an intact or impaired HPA axis, respectively, but intermediate values had only limited sensitivity and specificity. The criteria of HPA axis integrity, defined as an increment in plasma cortisol of more than 7 µg/dL above the baseline or as a doubling of the baseline cortisol value, were associated with high false positive and false negative rates. We conclude that 1) the baseline morning serum cortisol concentration has very limited predictive power in differentiating between normal and impaired HPA function; 2) the use of criteria based on incremental changes in serum cortisol from baseline leads to unacceptably high false positive and false negative rates; and 3) insulin hypoglycemia is still the best indicator of the integrity of the response of the HPA axis to stress.

This article has been cited by other articles:

				S. Fischli, S. Jenni, S. Allemann, M. Zwahlen, P. Diem, E. R. Christ, and C. Stettler Dehydroepiandrosterone Sulfate in the Assessment of the Hypothalamic-Pituitary-Adrenal Axis J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 539 - 542. [Abstract] [Full Text] [PDF]

				M. S. Cooper and P. M. Stewart Adrenal Insufficiency in Critical Illness J Intensive Care Med, November 1, 2007; 22(6): 348 - 362. [Abstract] [PDF]

				D. Zelena, L. Filaretova, Z. Mergl, I. Barna, Z. E. Toth, and G. B. Makara Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats Am J Physiol Endocrinol Metab, February 1, 2006; 290(2): E243 - E250. [Abstract] [Full Text] [PDF]

				J. R Greenfield and K. Samaras Evaluation of pituitary function in the fatigued patient: a review of 59 cases Eur. J. Endocrinol., January 1, 2006; 154(1): 147 - 157. [Abstract] [Full Text] [PDF]

				K Borm, M Slawik, F Beuschlein, L Seiler, F Flohr, A Berg, A Koenig, and M Reincke Low-dose glucose infusion after achieving critical hypoglycemia during insulin tolerance testing: effects on time of hypoglycemia, neuroendocrine stress response and patient's discomfort in a pilot study Eur. J. Endocrinol., October 1, 2005; 153(4): 521 - 526. [Abstract] [Full Text] [PDF]

				M Maghnie, E Uga, F Temporini, N Di Iorgi, A Secco, C Tinelli, A Papalia, M. Casini, and S Loche Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests Eur. J. Endocrinol., May 1, 2005; 152(5): 735 - 741. [Abstract] [Full Text] [PDF]

				P Mahachoklertwattana, K Sudkronrayudh, C Direkwattanachai, L Choubtum, and C Okascharoen Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate Arch. Dis. Child., November 1, 2004; 89(11): 1055 - 1058. [Abstract] [Full Text] [PDF]

				G. Francisco, C. Hernandez, R. Galard, and R. Simo Usefulness of Homeostasis Model Assessment for Identifying Subjects at Risk for Hypoglycemia Failure during the Insulin Hypoglycemia Test J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3408 - 3412. [Abstract] [Full Text] [PDF]

				I. L. Schmidt, H. Lahner, K. Mann, and S. Petersenn Diagnosis of Adrenal Insufficiency: Evaluation of the Corticotropin-Releasing Hormone Test and Basal Serum Cortisol in Comparison to the Insulin Tolerance Test in Patients with Hypothalamic-Pituitary-Adrenal Disease J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4193 - 4198. [Abstract] [Full Text] [PDF]

				K. Hussain, P. Hindmarsh, and A. Aynsley-Green Neonates with Symptomatic Hyperinsulinemic Hypoglycemia Generate Inappropriately Low Serum Cortisol Counterregulatory Hormonal Responses J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4342 - 4347. [Abstract] [Full Text] [PDF]

				R. I. Dorin, C. R. Qualls, and L. M. Crapo Diagnosis of Adrenal Insufficiency Ann Intern Med, August 5, 2003; 139(3): 194 - 204. [Abstract] [Full Text] [PDF]

				M. Schmiegelow, U. Feldt-Rasmussen, A. K. Rasmussen, M. Lange, H. S. Poulsen, and J. Muller Assessment of the Hypothalamo-Pituitary-Adrenal Axis in Patients Treated with Radiotherapy and Chemotherapy for Childhood Brain Tumor J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3149 - 3154. [Abstract] [Full Text] [PDF]

				M. S. Cooper and P. M. Stewart Corticosteroid Insufficiency in Acutely Ill Patients N. Engl. J. Med., February 20, 2003; 348(8): 727 - 734. [Full Text] [PDF]

				J. W. Finkelstein, D. E. Rusovici, E. Green, S. Foreman, H. E. Kulin, M. R. D'Arcangelo, and R. Kemezys Children with Organic Growth Hormone Deficiency Have Elevated Cortisol Responses to Stimuli J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2854 - 2856. [Abstract] [Full Text] [PDF]