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Steroid hormone synthesis is impaired in patients with severe sepsis

In patients with severe illness, adrenal insufficiency is often suspected and treatment with hydrocortisone has been shown to decrease mortality. However, the pathophysiology of an adrenal failure is only partially understood.

We analyzed the synthesis of different steroid hormones within the adrenal in severely ill patients in a prospective study using the established high dose stimulation test with synthetic cosyntropin.

Using commercially available essays, the steroid hormones progesterone, cortisole, testosterone, dehydroepiandrostenedione (DHEAS) and 17β-estradiol were determined before, and 30 and 60 min after stimulation with cosyntropin. Patients were characterized by scoring systems (APACHE II, SAPS II, MOD score). The underlying admission diagnosis grouped patients in septic, cardiogenic shock or control.

Sixty-five patients (22 in cardiogenic and 43 in septic shock, five and nine women, mean age 58 years, APACHE score of 20) were compared with 34 control patients (17 cancer patients, 10 healthy, four pulmonary emphysema and three other).

At baseline, septic and cardiogenic patients showed similar cortisol levels (21 and 21 μg/dl), higher than control (15 μg/dl, P < 0.05). Progesterone was increased fourfold (P < 0.001) in septic (1.2 ng/ml) and cardiogenic shock (1.1 ng/ml) compared with control (0.3 ng/ml). Men with sepsis had the highest β-estradiol levels. Baseline cortisol levels were only slightly higher in intensive care patients compared with control. There were no clear correlations between steroid hormones and scoring systems or laboratory signs of infections like CRP, PCT, leukocyte or platelet counts.

After stimulation with cosyntropin, testosterone, 17β-estradiol and DHEAS remained constant, whereas progesterone increased (P < 0.001) in all groups of patients without significant difference between groups. In control or cardiogenic patients cosyntropin stimulation leads to significantly increasing values of cortisol (P = 2.15 × 10-12 and P = 0.04); in patients with sepsis the increase of cortisol (P > 0.1) was blunted, however. This decrease in cortisol stimulation was independent of the use of sedatives or mechanical ventilation. In cardiogenic patients the increase in cortisol levels after stimulation was similar to control patients (7 μg/dl) and was not influenced by increasing dosage of catecholamines; in septic patients the cortisol increase was significantly lower (P < 0.01) with high catecholamines (2 μg/dl) than with low catecholamines (7 μg/dl).

At baseline, patients at the intensive care unit had higher progesterone levels than normal. Septic patients showed diminished response to cosyntropin stimulation regarding cortisol levels despite a normal increase of progesterone. This points to an impairment of cortisol synthesis.

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Angstwurm, M., Rashidi Kia, A., Schopohl, J. et al. Steroid hormone synthesis is impaired in patients with severe sepsis. Crit Care 7, P003 (2003).

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  • Cortisol
  • Progesterone
  • Cortisol Level
  • Septic Patient
  • Cardiogenic Shock