Hypothalamic-pituitary-adrenal axis in mechanically ventilated critically ill patients: incidence of hyporesponsiveness to stimulation and relationship to cytokine levels

The incidence of hypothalamic-pituitary-adrenal (HPA) axis hypo-responsiveness to stimulation and its relationship to cytokine levels in mechanically ventilated critically ill patients remain controversial. To further clarify these issues, 42 patients (33 men) with a median age of 57 years (range: 16–81 years) were enrolled. Underlying diagnoses included postoperative cases (n = 20), multiple trauma without head injury (n = 12), pancreatitis (n = 4), and miscellaneous (n = 8). Endocrine testing was performed 3–14 days (median: 6 days) after ICU admission. The median APACHE II score at the day of endocrine testing was 15 and the mean SOFA score was 9 ± 4. Morning blood samples were collected for the determination of baseline cortisol, corticotropin (ACTH), and cytokines including IL-8, IL-1, IL-6, IL-12p70 and TNF-α. Immediately after, a low-dose stimulation test (LDST) was performed: 1 μg freshly prepared tetra-cosactrin (1–24) was administered as an intravenous bolus and 30 min later a second blood specimen was obtained to measure stimulated cortisol. Patients having stimulated cortisol levels less than 20 μg/dl were defined as nonresponders to the LDST.

The mean baseline cortisol was 16 ± 6 μg/dl (range: 3–32 μg/dl). The mean stimulated cortisol and the increment in cortisol were and 21 ± 6 μg/dl (range: 11–42 μg/dl) and 6 ± 4 μg/dl (range: 0–20 μg/dl), respectively. The median ACTH was 19.0 pg/ml (range: 2–300 pg/ml). Fifteen patients (36%) were nonresponders to the LDST.

In the entire patient population median cytokine levels were as follows: IL-8 = 133 pg/ml (range: 11–1010 pg/ml); IL-1 = 51 pg/ml (range: 0–282 pg/ml); TNF-α = 1 pg/ml (range: 0–16 pg/ml); and IL-12p70 = 8 pg/ml (range: 0–47 pg/ml). Nonresponders to the LDST had higher values for IL-1 (45 pg/ml vs 16 pg/ml, P < 0.05) and IL-12p70 (11 pg/ml vs 3 pg/ml, P < 0.05) compared with responders. The two groups did not differ with regard to the other cytokine concentrations.

In conclusion, adrenal cortisol secretion after dynamic stimulation is deficient in about two-thirds of critically ill patients; this disorder is associated with higher IL-1 and IL-12p70 levels.