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 Berneis, K. Articles by Müller, B. Search for Related Content PubMed PubMed Citation Articles by Berneis, K. Articles by Müller, B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HYDROCORTISONE METYRAPONE

Combined Stimulation of Adrenocorticotropin and Compound-S by Single Dose Metyrapone Test as an Outpatient Procedure to Assess Hypothalamic-Pituitary-Adrenal Function

Division of Endocrinology, Diabetology and Clinical Nutrition, Department of Internal Medicine, University Hospitals, CH-4031 Basel, Switzerland

Address all correspondence and requests for reprints to: Kaspar Berneis, M.D., University Hospital Bruderholz, Department of Internal Medicine, 4101 Bottmingen, Switzerland. E-mail: kaspar{at}berneis.ch.

Abstract

The metyrapone test is used to test the hypothalamic-pituitary-adrenocortical axis. The present study aims to assess the diagnostic accuracy of combined stimulation of ACTH and compound-S (CMP-S). In addition, we analyzed the safety and practicability of this test as an outpatient procedure.

A total of 327 metyrapone tests were analyzed retrospectively in 185 patients (mean age, 50.3 ± 15.2 yr). One hundred thirteen patients had one test, and 72 patients had between 2 and 6 tests over 1–3 yr. Most patients suffered from pituitary adenomas (60 macroadenomas, 63 microadenomas) or other pituitary lesions (n = 29). Metyrapone (2 g) was given at 2400 h as an outpatient procedure. Blood samples for analysis of ACTH, CMP-S, and cortisol were taken at 0730 h.

Stimulation of adrenal CMP-S and cortisol by pituitary ACTH demonstrated a dose-response curve with the shape of half a geometric parabola. CMP-S reached a plateau when ACTH rose above 175 ng/liter [r = 0.661, P < 0.0001 for ACTH <175 ng/liter; r = 0.083, P = not significant (NS) for ACTH >175 ng/liter], cortisol flattened at ACTH levels above 230 ng/liter (r = 0.633; P < 0.0001 for ACTH < 230 ng/liter; P = NS for ACTH >230 ng/liter). Alternatively, the sum of CMP-S plus cortisol also flattened when ACTH rose above 230 ng/liter (r = 0.696; P < 0.0001 for ACTH <230; P = NS for ACTH > 230 ng/liter).

Receiver operating curve analysis defining a cut-off for ACTH at 150 ng/liter demonstrated a sensitivity of 47% and 67% at a cut-off level for CMP-S at 200 or 260 nmol/liter, respectively. The respective specificity was 82% and 68% for CMP-S. This compared with a sensitivity of 71% and specificity of 69% if the sum of CMP-S plus cortisol of 450 nmol/liter were used as cut-off.

The response curve between CMP-S and ACTH implies a maximally stimulated adrenal cortex at circulating ACTH levels above 175 ng/liter. Single measurement of CMP-S using the cut-off at 200 nmol/liter, as suggested in the literature, yields a poor sensitivity of only 47% compared with ACTH. Despite the relatively high cross-reactivity of CMP-S in the cortisol assay, the sum of CMP-S and cortisol levels with a cut-off value of 450 nmol/liter yields a better diagnostic accuracy compared with CMP-S alone.

This article has been cited by other articles:

				R. F. A. de Lind van Wijngaarden, B. J. Otten, D. A. M. Festen, K. F. M. Joosten, F. H. de Jong, F. C. G. J. Sweep, and A. C. S. Hokken-Koelega High Prevalence of Central Adrenal Insufficiency in Patients with Prader-Willi Syndrome J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1649 - 1654. [Abstract] [Full Text] [PDF]

				Z. Thomas and G. L Fraser An Update on the Diagnosis of Adrenal Insufficiency and the Use of Corticotherapy in Critical Illness Ann. Pharmacother., September 1, 2007; 41(9): 1456 - 1465. [Abstract] [Full Text] [PDF]

				R. Aneja and J. A Carcillo What is the rationale for hydrocortisone treatment in children with infection-related adrenal insufficiency and septic shock? Arch. Dis. Child., February 1, 2007; 92(2): 165 - 169. [Abstract] [Full Text] [PDF]

				R. Salvatori Adrenal Insufficiency JAMA, November 16, 2005; 294(19): 2481 - 2488. [Abstract] [Full Text] [PDF]

				M. F. Dallman Adrenocortical function, feedback, and alphabet soup Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E361 - E362. [Abstract] [Full Text] [PDF]

				I. E. Widmer, J. J. Puder, C. Konig, H. Pargger, H. R. Zerkowski, J. Girard, and B. Muller Cortisol Response in Relation to the Severity of Stress and Illness J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4579 - 4586. [Abstract] [Full Text] [PDF]

				P. Y. Liu, S. M. Pincus, D. M. Keenan, F. Roelfsema, and J. D. Veldhuis Joint synchrony of reciprocal hormonal signaling in human paradigms of both ACTH excess and cortisol depletion Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E160 - E165. [Abstract] [Full Text] [PDF]

				E. S. Nylen and B. Muller Endocrine Changes in Critical Illness J Intensive Care Med, March 1, 2004; 19(2): 67 - 82. [Abstract] [PDF]