Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin

Because high circulating levels of glucocorticoids impair immunity and pred ispose to infections, we evaluated whether indices of cortisol (F) producti on could predict infections in patients with Gushing syndrome (GS) caused b y ectopic production of ACTH (EA). Charts of 54 consecutive patients with untreated EA, without underlying dia gnosis of small cell carcinoma of the lung, were reviewed, and types of inf ections, white blood cell (WBC) count, fever, as well as the glucocorticoid indices [0800 h F, daily urine F excretion (UFC), and daily urine 17-hydro xysteroid/g creatinine excretion (17OHS)], were recorded. Thirty-five patients had no or clinically mild infection; the remaining 19 patients had severe, systemic infection (n = 13) and/or sepsis (n = 6), inc luding either bacterial or opportunistic pathogens or both (73.7%, 42.1%, a nd 13.8%, respectively). The latter group of patients had significantly hig her indices of hypercortisolism (F, UFC, and 17OHS) than those with mild or no infections, but these indices did not correlate with temperature or WBC count. Thresholds for identifying severe infection were selected for maxim al positive predictive value and were: F, 43.1 mu g/dL; UFC, 2000 mu g/day; and 17OHS, 35 mg/g creatinine. The most accurate discriminator for severe infection was 17OHS, based on a positive predictive value of 64.7%. Our data strongly suggests that the likelihood for a bacterial or opportuni stic infection in CS patients, even without underlying small cell carcinoma of the lung, is greatest in patients with extreme hypercortisolism. The pr edictive value of total WBC count or the presence of an elevated temperatur e is not sufficient to identify patients with severe, life-threatening infe ction.