Dissection of Hypothalamic-Pituitary-Adrenal Axis Pathology in 1-Month-Abstinent Alcohol-Dependent Men, Part 1: Adrenocortical and Pituitary Glucocorticoid Responsiveness

Authors

  • Bryon Adinoff,

    Corresponding author
    1. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (BA, SRK, MJW); the Veterans Affairs North Texas Health Care System, Dallas, Texas (BA); PrimaCare Medical Center, Dallas, Texas (PAC); and the Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (WE, MBB).
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  • Steven R. Krebaum,

    1. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (BA, SRK, MJW); the Veterans Affairs North Texas Health Care System, Dallas, Texas (BA); PrimaCare Medical Center, Dallas, Texas (PAC); and the Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (WE, MBB).
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  • Patricia A. Chandler,

    1. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (BA, SRK, MJW); the Veterans Affairs North Texas Health Care System, Dallas, Texas (BA); PrimaCare Medical Center, Dallas, Texas (PAC); and the Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (WE, MBB).
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  • Wen Ye,

    1. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (BA, SRK, MJW); the Veterans Affairs North Texas Health Care System, Dallas, Texas (BA); PrimaCare Medical Center, Dallas, Texas (PAC); and the Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (WE, MBB).
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  • Morton B. Brown,

    1. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (BA, SRK, MJW); the Veterans Affairs North Texas Health Care System, Dallas, Texas (BA); PrimaCare Medical Center, Dallas, Texas (PAC); and the Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (WE, MBB).
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  • Mark J. Williams

    1. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (BA, SRK, MJW); the Veterans Affairs North Texas Health Care System, Dallas, Texas (BA); PrimaCare Medical Center, Dallas, Texas (PAC); and the Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (WE, MBB).
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  • Supported by Grant AA1570 from the National Institute on Alcohol Abuse and Alcoholism and Grant M01-RR00633 from USPHS. Presented at the 57th Annual Convention of the Society of Biological Psychiatry, May 18, 2002, Philadelphia, Pennsylvania; the 2003 Scientific Meeting of the Research Society on Alcoholism, June 22, 2003, Ft. Lauderdale, Florida; and the 12th World Congress on Biomedical Alcohol Research, October 1, 2004, Heidelberg/Mannheim, Germany.

Reprint requests: Bryon Adinoff, MD, 116A5, Dallas VAMC, 4500 South Lancaster Road, Dallas, Texas 75216; Fax: 214-857-0902; E-mail: bryon.adinoff@utsouthwestern.edu

Abstract

Background:

Long-term ingestion of alcohol produces marked alterations in hypothalamic-pituitary-adrenal axis activity. The authors engaged in a series of studies to determine the distinct role of the hypothalamus and the pituitary and adrenal glands in the disturbances observed in abstinent alcohol-dependent subjects. In this first of a two-part study, the authors report on (1) the basal secretory profile of corticotropin and cortisol from 2000 to 0800 hrs, (2) adrenocortical sensitivity in both the presence and absence of endogenous pituitary activation, and (3) pituitary glucocorticoid sensitivity to dexamethasone.

Methods:

Eleven male, 4 to 6 weeks abstinent, alcohol-only–dependent subjects and 10 age-matched male healthy controls were studied. Basal circulating concentrations of corticotropin and cortisol were obtained from 2000 to 0800 hr. A submaximal dose of cosyntropin (0.01 μg/kg), a corticotropin analogue was then administered to assess adrenocortical sensitivity. In a separate session, cosyntropin was administered following high-dose dexamethasone (8 mg iv) to assess adrenocortical sensitivity in the relative absence of endogenous corticotropin. In addition, the corticotropin response to dexamethasone was measured to determine pituitary glucocorticoid responsiveness.

Results:

Cortisol, but not corticotropin, pulse amplitude (p < 0.05) and mean concentration (p = 0.05) was significantly lower in alcohol-dependent subjects compared with controls. The cortisol response to cosyntropin was lower in alcohol-dependent subjects following endogenous corticotropin suppression by high-dose dexamethasone (p < 0.04) but not without dexamethasone pretreatment. Mean corticotropin (p < 0.004) and cortisol (p < 0.05) concentrations in response to dexamethasone were attenuated in the patients compared to controls. Basal concentrations of 11-deoxycortisol, the precursor to cortisol, were also decreased in alcohol-dependent subjects (p < 0.05).

Conclusion:

Attenuated basal and stimulated adrenocortical concentrations in abstinent alcohol-dependent men are coupled with a nonhomeostatic increase in pituitary glucocorticoid inhibition. A decrease in stress-axis responsivity in alcohol dependence may have implications for treatment outcome.

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