Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: adrenocortical and pituitary glucocorticoid responsiveness

Alcohol Clin Exp Res. 2005 Apr;29(4):517-27. doi: 10.1097/01.alc.0000158940.05529.0a.


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 microg/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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex / drug effects
  • Adrenal Cortex / metabolism
  • Adrenal Cortex / physiology*
  • Adrenal Cortex Hormones / metabolism
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Alcoholism / metabolism
  • Alcoholism / pathology*
  • Alcoholism / psychology
  • Cortodoxone / blood
  • Cosyntropin
  • Dexamethasone
  • Glucocorticoids / metabolism
  • Glucocorticoids / pharmacology*
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / urine
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / pathology*
  • Male
  • Middle Aged
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism
  • Pituitary Gland / physiology*
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / pathology*
  • Temperance*


  • Adrenal Cortex Hormones
  • Glucocorticoids
  • Cosyntropin
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Cortodoxone
  • Hydrocortisone