Patients with Septic Shock Show Impaired Adrenal Hormone Synthesis

In patients with severe illness, adrenal insufficiency is often suspected and treatment with hydrocortisone and fludrocortisone has been shown to decrease mortality. However, the pathophysiology of adrenal failure is not understood.

Using commercially available essays, the steroid hormones aldosterone, progesterone, 17-OH progesterone, cortisol, testosterone, dehydroepiandrostenedione, and 17β-estradiol were determined before, 30 and 60 minutes after stimulation with 250 µg cosyntropin. The underlying admission diagnosis grouped patients in septic (n = 43, 5 women) and cardiogenic (n = 22, 9 women) shock or control (n = 34).

Septic and cardiogenic patients showed similar baseline cortisol levels that were higher than in controls. Aldosterone in septic patients was similar to controls and lower than in cardiogenic shock patients. Baseline active renin was low in controls (25 µU/ml), but elevated in septic (250 µU/ml) and cardiogenic (3000 µU/ml) shock patients. Progesterone was increased 4-fold (p < 0.001) in septic (1.2 ng/ml) and cardiogenic shock patients (1.1 ng/ml) compared to controls (0.3 ng/ml). In addition 17-OH progesterone was increased in both groups of patients compared to controls (p < 0.05). After stimulation, testosterone, 17β-estradiol and DHEAS remained constant, whereas progesterone and 17-OH progesterone increased (p < 0.001) in all groups without significant differences. In control or cardiogenic patients, stimulation leads to significantly increasing values of cortisol and aldosterone (p = 2.15 × 10^– 12 and p = 0.04, respectively); in patients with sepsis cortisol and aldosterone stimulation was blunted, however. This diminished cortisol stimulation was independent of the use of sedatives. The increment of serum cortisone after stimulation in the septic group correlated inversely to baseline progesterone and 17-OH progesterone, but not to baseline cortisol levels.

At baseline, patients with septic or cardiogenic shock had higher progesterone and 17-OH progesterone levels but only slightly elevated cortisol levels compared to controls. Septic patients showed diminished response to cosyntropin stimulation for both cortisol and aldosterone levels despite a normal increase in progesterone and 17-OH progesterone cortisol precursors. This impaired steroid hormone synthesis at 21-hydroxylase or 11-hydroxylase enzyme level may have clinical implications in patients with septic shock.