Stimulation of the Hypothalamic-Pituitary-Adrenal Axis with the Opioid Antagonist Nalmefene

Stimulation of the Hypothalamic-Pituitary-Adrenal Axis with the Opioid Antagonist Nalmefene Nalmefene Stimulation of the HPA Axis. Background: The Hypothalamic-pituitary-adrenal (HPA) axis plays a vital role in the body's response to stress. The traditional gold standard for evaluating the HPA axis, the insulin hypoglycemia test (IHT), has several known limitations, and a second test, the standard ACTH stimulation test, can detect severe deficiencies of cortisol, but often misses mild or early cases. Therefore, a better test for the evaluation of the HPA axis is needed. This study evaluated the opiate antagonist nalmefene as a stimulation test of the HPA axis. Methods: 25 healthy subjects were studied, 9 women and 16 men, mean age 30.4 yr. (range 21–55), and mean BMI 24.1 kg/m2 (range 18.6–34.2). Subjects received one of 3 doses of intravenously administered nalmefene: 2 mg (n = 6), 6 mg (n = 12), or 10 mg (n = 7). Serum cortisol and plasma ACTH were measured before and serially over two hours after the administration of nalmefene. Results: ACTH and cortisol levels rose significantly and similarly after the 10 mg dose and the 6 mg dose. After the 10 mg dose, mean peak ACTH was 82.4 ± 22.6 pg/ml and mean peak cortisol was 25.2 ± 1.8 μg/dl. After the 6 mg dose, mean peak ACTH was 70.3 ± 7.7 pg/ml and mean peak cortisol was 24.7 ± 1.7 μg/dl. Cortisol levels rose above 18 μg/dl in all subjects receiving 10 mg of nalmefene, and in all but two of the subjects receiving 6 mg of nalmefene. Side effects to nalmefene were of greater duration and intensity in the subjects receiving 10 mg of nalmefene vs. those receiving 6 or 2 mg. These included most notably fatigue, lightheadedness, nausea and vomiting. Conclusions: Of the nalmefene doses we studied, 6 mg achieved the best combination of stimulation of ACTH and cortisol and fewest side effects. If further studies show a concordance between nalmefene and IHT, nalmefene testing could be used to assess the HPA axis in patients at risk for dysfunction of this axis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pituitary Springer Journals

Stimulation of the Hypothalamic-Pituitary-Adrenal Axis with the Opioid Antagonist Nalmefene

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Publisher
Springer Journals
Copyright
Copyright © 2005 by Springer Science + Business Media, Inc.
Subject
Medicine & Public Health; Diabetes; Neurosurgery
ISSN
1386-341X
eISSN
1573-7403
DOI
10.1007/s11102-005-5227-6
Publisher site
See Article on Publisher Site

Abstract

Nalmefene Stimulation of the HPA Axis. Background: The Hypothalamic-pituitary-adrenal (HPA) axis plays a vital role in the body's response to stress. The traditional gold standard for evaluating the HPA axis, the insulin hypoglycemia test (IHT), has several known limitations, and a second test, the standard ACTH stimulation test, can detect severe deficiencies of cortisol, but often misses mild or early cases. Therefore, a better test for the evaluation of the HPA axis is needed. This study evaluated the opiate antagonist nalmefene as a stimulation test of the HPA axis. Methods: 25 healthy subjects were studied, 9 women and 16 men, mean age 30.4 yr. (range 21–55), and mean BMI 24.1 kg/m2 (range 18.6–34.2). Subjects received one of 3 doses of intravenously administered nalmefene: 2 mg (n = 6), 6 mg (n = 12), or 10 mg (n = 7). Serum cortisol and plasma ACTH were measured before and serially over two hours after the administration of nalmefene. Results: ACTH and cortisol levels rose significantly and similarly after the 10 mg dose and the 6 mg dose. After the 10 mg dose, mean peak ACTH was 82.4 ± 22.6 pg/ml and mean peak cortisol was 25.2 ± 1.8 μg/dl. After the 6 mg dose, mean peak ACTH was 70.3 ± 7.7 pg/ml and mean peak cortisol was 24.7 ± 1.7 μg/dl. Cortisol levels rose above 18 μg/dl in all subjects receiving 10 mg of nalmefene, and in all but two of the subjects receiving 6 mg of nalmefene. Side effects to nalmefene were of greater duration and intensity in the subjects receiving 10 mg of nalmefene vs. those receiving 6 or 2 mg. These included most notably fatigue, lightheadedness, nausea and vomiting. Conclusions: Of the nalmefene doses we studied, 6 mg achieved the best combination of stimulation of ACTH and cortisol and fewest side effects. If further studies show a concordance between nalmefene and IHT, nalmefene testing could be used to assess the HPA axis in patients at risk for dysfunction of this axis.

Journal

PituitarySpringer Journals

Published: Dec 23, 2005

References

  • Adrenal Insufficiency
    Oelkers, W
  • Value of Basal Plasma Cortisol Assays in the Assessment of Pituitary-Adrenal Insufficiency
    Hagg, E; Asplund, K; Lithner, F
  • Opiate Modulation of the Pituitary-Adrenal Axis: Effects of Stress and Circadian Rhythm
    Grossman, A; Gaillard, RC; McCartney, P; Rees, LH; Besser, GM
  • Nalmefene Causes Greater Hypothalamic-Pituitary Adrenal Axis Activation than Naloxone in Normal Volunteers: Implications for the Treatment of Alcoholism
    Schluger, J; Ho, A; Borg, L
  • Assessing the Hypothalamo-Pituitary-Adrenocortical Axis Using Physiological Doses of Adrenocorticotropic Hormone
    Talwar, V; Lodha, S; Dash, RJ
  • Adrenocorticotropin Stimulation Tests in Patients with Hypothalamic-Pituitary Disease: Low dose, Standard High Dose and 8-h Infusion Tests
    Nye, EJ; Grice, JE; Hockings, GI
  • The Low-Dose ACTH Test Does Not Provide a Useful Assessment of the Hypothalamic-Pituitary-Adrenal Axis in Secondary Adrenal Insufficiency
    Suliman, AM; Smith, TP; Labib, M; Fiad, TM; McKenna, TJ
  • A Double-Blind, Placebo-Controlled Study of Oral Nalmefene for Alcohol Dependence
    Mason, B; Salvato, F; Williams, L; Rivto, E; Cutler, R

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