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Cortisolemic Indices Predict Severe Infections in Cushing Syndrome Due to Ectopic Production of Adrenocorticotropin¹

Clinical Endocrinology Branch, National Institute of Diabetes, Digestive, and Kidney Diseases (N.J.S.); Pediatric Oncology Branch, Division of Clinical Sciences, National Cancer Institute (S.J.C.); and Developmental Endocrinology Branch, National Institute of Child Health and Human Development (L.K.N.), National Institutes of Health, Bethesda, Maryland 20892

Address correspondence and requests for reprints to: Lynnette K. Nieman, M.D., Clinical Director, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 9S261, 10 Center Drive, MSC 1834, Bethesda, Maryland 20892-1834. E-mail: niemanl{at}nih.gov

Because high circulating levels of glucocorticoids impair immunity and predispose to infections, we evaluated whether indices of cortisol (F) production could predict infections in patients with Cushing syndrome (CS) caused by ectopic production of ACTH (EA).

Charts of 54 consecutive patients with untreated EA, without underlying diagnosis of small cell carcinoma of the lung, were reviewed, and types of infections, white blood cell (WBC) count, fever, as well as the glucocorticoid indices [0800 h F, daily urine F excretion (UFC), and daily urine 17-hydroxysteroid/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), including either bacterial or opportunistic pathogens or both (73.7%, 42.1%, and 13.8%, respectively). The latter group of patients had significantly higher 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 maximal positive predictive value and were: F, 43.1 µg/dL; UFC, 2000 µg/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 opportunistic infection in CS patients, even without underlying small cell carcinoma of the lung, is greatest in patients with extreme hypercortisolism. The predictive value of total WBC count or the presence of an elevated temperature is not sufficient to identify patients with severe, life-threatening infection.

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