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Background and Aims <p>The pathogenesis of adrenal dysfunction (AD) in cirrhosis is incompletely understood. We aimed to evaluate potential effects of cirrhosis on hypothalamic–pituitary–adrenal axis (HPA) functionality in stable outpatients with decompensated disease.</p> Methods <p>Outpatients with decompensated cirrhosis were prospectively recruited at a transplant center. Biomarkers reflective of HPA activity, glucocorticoid synthesis, cholesterol metabolism, systemic neurohormonal activity, and the immune system were measured prior to administration of a standard-dose adrenocorticotrophic hormone (ACTH) stimulation test. Adrenal dysfunction was defined as an increase in serum total cortisol level (delta TC) of &lt; 9&#xa0;µg/dL. Patients were followed for up to 12&#xa0;months for assessment of clinical outcomes including portal hypertension-related decompensation, hospitalization, liver transplant, and death.</p> Results <p>Seventy-six participants were enrolled (AD 33%, normal adrenal function 67%). Median ACTH levels were similar between groups (<i>P</i> = 0.581). The product ratio of the cortisol precursor 17-hydroxyprogesterone to 11-deoxycortisol (11-DOC) was lower in the AD group (0.9 vs. 1.3, <i>P</i> = 0.036), whereas the 11-DOC:cortisol ratio was similar between groups (5.9 vs. 5.0, <i>P</i> = 0.522). Of the 13 measured serum cytokines, only median levels of IL-6 were significantly higher in the AD group (14.71 vs. 8.99&#xa0;pg/mL, <i>P</i> = 0.024). There were no differences in clinical outcomes between groups.</p> Conclusions <p>Inappropriately low ACTH secretion and alterations in adrenal steroidogenesis are associated with an abnormal response to ACTH stimulation testing in outpatients with decompensated cirrhosis. These findings suggest multilevel HPA axis dysfunction and support the theory that AD represents cirrhosis-induced extrahepatic organ failure. The presence of AD may not be associated with worse liver-related outcomes.</p>

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Adrenal Dysfunction in Outpatients with Decompensated Cirrhosis: Impairment in the Hypothalamic–Pituitary–Adrenal Axis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月26日

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  • Brian J. Wentworth,
  • Calvin X. Geng,
  • Wendy M. Novicoff,
  • Helmy M. Siragy,
  • Zachary H. Henry

摘要

Background and Aims

The pathogenesis of adrenal dysfunction (AD) in cirrhosis is incompletely understood. We aimed to evaluate potential effects of cirrhosis on hypothalamic–pituitary–adrenal axis (HPA) functionality in stable outpatients with decompensated disease.

Methods

Outpatients with decompensated cirrhosis were prospectively recruited at a transplant center. Biomarkers reflective of HPA activity, glucocorticoid synthesis, cholesterol metabolism, systemic neurohormonal activity, and the immune system were measured prior to administration of a standard-dose adrenocorticotrophic hormone (ACTH) stimulation test. Adrenal dysfunction was defined as an increase in serum total cortisol level (delta TC) of < 9 µg/dL. Patients were followed for up to 12 months for assessment of clinical outcomes including portal hypertension-related decompensation, hospitalization, liver transplant, and death.

Results

Seventy-six participants were enrolled (AD 33%, normal adrenal function 67%). Median ACTH levels were similar between groups (P = 0.581). The product ratio of the cortisol precursor 17-hydroxyprogesterone to 11-deoxycortisol (11-DOC) was lower in the AD group (0.9 vs. 1.3, P = 0.036), whereas the 11-DOC:cortisol ratio was similar between groups (5.9 vs. 5.0, P = 0.522). Of the 13 measured serum cytokines, only median levels of IL-6 were significantly higher in the AD group (14.71 vs. 8.99 pg/mL, P = 0.024). There were no differences in clinical outcomes between groups.

Conclusions

Inappropriately low ACTH secretion and alterations in adrenal steroidogenesis are associated with an abnormal response to ACTH stimulation testing in outpatients with decompensated cirrhosis. These findings suggest multilevel HPA axis dysfunction and support the theory that AD represents cirrhosis-induced extrahepatic organ failure. The presence of AD may not be associated with worse liver-related outcomes.