{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:02:56Z","timestamp":1777039376864,"version":"3.51.4"},"reference-count":43,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:p>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).<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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 \u03bcg\/dL; UFC, 2000 \u03bcg\/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%.<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1210\/jcem.85.1.6294","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:05:28Z","timestamp":1389200728000},"page":"42-47","source":"Crossref","is-referenced-by-count":13,"title":["Cortisolemic Indices Predict Severe Infections in Cushing Syndrome Due to Ectopic Production of Adrenocorticotropin1"],"prefix":"10.1210","volume":"85","author":[{"given":"Nicholas J.","family":"Sarlis","sequence":"first","affiliation":[{"name":"Clinical Endocrinology Branch, National Institute of Diabetes, Digestive, and Kidney Diseases (N.J.S.), Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Chanock","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, Division of Clinical Sciences, National Cancer Institute (S.J.C.), Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynnette K.","family":"Nieman","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Branch, National Institute of Child Health and Human Development (L.K.N.), National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071617480807600_R1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/0002-9343(52)90027-2","article-title":"The natural history of Cushing\u2019s syndrome.","volume":"13","author":"Plotz","year":"1952","journal-title":"Am J Med"},{"key":"2020071617480807600_R2","first-page":"45","article-title":"Corticosteroids and infections.","volume":"9","author":"Kass","year":"1958","journal-title":"Adv Intern Med"},{"key":"2020071617480807600_R3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1056\/NEJM197107292850501","article-title":"Results of treatment in 108 patients with Cushing\u2019s syndrome.","volume":"285","author":"Orth","year":"1971","journal-title":"N Engl J Med"},{"key":"2020071617480807600_R4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3949\/ccjm.49.1.43","article-title":"Opportunistic infections in patients with ectopic ACTH-secreting tumors.","volume":"49","author":"Higgins","year":"1982","journal-title":"Cleve Clin Q"},{"key":"2020071617480807600_R5","doi-asserted-by":"crossref","first-page":"334","DOI":"10.7326\/0003-4819-101-3-334","article-title":"Opportunistic infections in endogenous Cushing\u2019s syndrome.","volume":"101","author":"Graham","year":"1984","journal-title":"Ann Intern Med"},{"key":"2020071617480807600_R6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/1097-0142(19920101)69:1<66::AID-CNCR2820690113>3.0.CO;2-2","article-title":"Paraneoplastic Cushing\u2019s syndrome as an adverse prognostic factor in patients who die early with small-cell lung cancer.","volume":"69","author":"Dimopoulos","year":"1992","journal-title":"Cancer"},{"key":"2020071617480807600_R7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1200\/JCO.1992.10.1.21","article-title":"Cushing\u2019s syndrome associated with ectopic corticotropin production and small-cell lung cancer.","volume":"10","author":"Shepherd","year":"1992","journal-title":"J Clin Oncol"},{"key":"2020071617480807600_R8","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1001\/archinte.1993.00410060054009","article-title":"Ectopic corticotropin syndrome and small-cell carcinoma of the lung.","volume":"153","author":"Delisle","year":"1993","journal-title":"Arch Intern Med"},{"key":"2020071617480807600_R9","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S0025-7125(16)32228-3","article-title":"Corticosteroids and infectious diseases.","volume":"57","author":"Dale","year":"1973","journal-title":"Med Clin North Am"},{"key":"2020071617480807600_R10","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1172\/JCI107544","article-title":"The effects of in vivo hydrocortisone on subpopulations of human lymphocytes.","volume":"53","author":"Fauci","year":"1974","journal-title":"J Clin Invest"},{"key":"2020071617480807600_R11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1600-065X.1982.tb00431.x","article-title":"Corticosteroid-mediated immunoregulation in man.","volume":"65","author":"Cupps","year":"1982","journal-title":"Immunol Rev"},{"key":"2020071617480807600_R12","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1093\/clinids\/11.6.954","article-title":"Risk of infectious complications in patients taking glucocorticosteroids.","volume":"11","author":"Stuck","year":"1989","journal-title":"Rev Infect Dis"},{"key":"2020071617480807600_R13","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.7326\/0003-4819-119-12-199312150-00007","article-title":"Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates.","volume":"119","author":"Boumpas","year":"1993","journal-title":"Ann Intern Med"},{"key":"2020071617480807600_R14","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0889-8529(18)30091-4","article-title":"Glucocorticoids and infection.","volume":"23","year":"1994","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2020071617480807600_R15","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/00043426-199709000-00001","article-title":"Alterations in immune function of children undergoing therapy for cancer.","volume":"19","author":"Lehrnbecher","year":"1997","journal-title":"Am J Pediatr Hematol Oncol"},{"key":"2020071617480807600_R16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1210\/edrv-5-1-25","article-title":"Physiological functions of glucocorticoid in stress and their relationship to pharmacological actions.","volume":"5","author":"Munck","year":"1984","journal-title":"Endocr Rev"},{"key":"2020071617480807600_R17","first-page":"97","article-title":"New mechanisms for effects of anti-inflammatory glucocorticoids.","volume":"3","year":"1991","journal-title":"Biofactors"},{"key":"2020071617480807600_R18","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/21548331.1992.11705486","article-title":"The effects of glucocorticoid therapy.","volume":"27","year":"1992","journal-title":"Hospital Pract"},{"key":"2020071617480807600_R19","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1126\/science.270.5234.286","article-title":"Immunosuppression by glucocorticoids: inhibition of NF-\u03baB activity through induction of I\u03baB synthesis.","volume":"270","author":"Auphan","year":"1995","journal-title":"Science"},{"key":"2020071617480807600_R20","first-page":"173","article-title":"Minimizing the side effects of glucocorticoid therapy.","volume":"35","year":"1990","journal-title":"Adv Intern Med"},{"key":"2020071617480807600_R21","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0889-857X(05)70327-6","article-title":"Infectious complications of immunosuppressive therapy in patients with rheumatic diseases.","volume":"23","author":"Segal","year":"1997","journal-title":"Rheum Dis Clin North Am"},{"key":"2020071617480807600_R22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0140-6736(91)93374-I","article-title":"Effect of mitotane on Alternaria alternata infection in Cushing\u2019s syndrome.","volume":"337","author":"Kasperlik-Zaluska","year":"1991","journal-title":"Lancet"},{"key":"2020071617480807600_R23","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1056\/NEJM199109263251301","article-title":"Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing\u2019s syndrome.","volume":"325","author":"Oldfield","year":"1991","journal-title":"N Engl J Med"},{"key":"2020071617480807600_R24","doi-asserted-by":"crossref","first-page":"211","DOI":"10.7326\/0003-4819-116-3-211","article-title":"Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome.","volume":"116","author":"Flack","year":"1992","journal-title":"Ann Intern Med"},{"key":"2020071617480807600_R25","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1210\/jcem.78.2.8106630","article-title":"A comparison of the standard high dose dexamethasone suppression test and the overnight 8-mg dexamethasone suppression test for the differential diagnosis of adrenocorticotropin-dependent Cushing\u2019s syndrome.","volume":"78","author":"Dichek","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071617480807600_R26","first-page":"1308","article-title":"A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing\u2019s syndrome.","volume":"77","author":"Nieman","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071617480807600_R27","first-page":"434","article-title":"Increased adrenocortical activity and malignant disease.","volume":"2","author":"Farrant","year":"1950","journal-title":"Lancet"},{"key":"2020071617480807600_R28","doi-asserted-by":"crossref","first-page":"58","DOI":"10.7326\/0003-4819-63-1-58","article-title":"Cushing\u2019s syndrome due to islet cell carcinoma of the pancreas: report of two cases, one with elevated 5-hydroxyindole acetic acid and complicated by aspergillosis.","volume":"63","author":"Sayle","year":"1965","journal-title":"Ann Intern Med"},{"key":"2020071617480807600_R29","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1001\/archinte.1978.03630310081027","article-title":"Disseminated Strongyloides stercoralis infection. Association with ectopic ACTH syndrome and depressed cell-medicated immunity.","volume":"138","author":"Cummings","year":"1978","journal-title":"Arch Intern Med"},{"key":"2020071617480807600_R30","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1001\/archinte.1981.00340090123028","article-title":"Invasive aspergillosis complication Cushing\u2019s syndrome.","volume":"141","author":"Walsh","year":"1981","journal-title":"Arch Intern Med"},{"key":"2020071617480807600_R31","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1002\/1097-0142(19810615)47:12<2933::AID-CNCR2820471233>3.0.CO;2-G","article-title":"Combined pneumocystis carinii and nocardia asteroides pneumonia in a patient with an ACTH-producing carcinoid.","volume":"47","author":"Natale","year":"1981","journal-title":"Cancer"},{"key":"2020071617480807600_R32","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1001\/archinte.1983.00350110169033","article-title":"Pulmonary cryptococcosis and Cushing\u2019s syndrome.","volume":"143","author":"Kramer","year":"1983","journal-title":"Arch Intern Med"},{"key":"2020071617480807600_R33","first-page":"188","article-title":"Endogenous Cushing\u2019s syndrome complicated by Pneumocystis carinii pneumonia.","volume":"129","author":"Fulkerson","year":"1984","journal-title":"Am Rev Respir Dis"},{"key":"2020071617480807600_R34","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1001\/archinte.1989.00390110133029","article-title":"Three opportunistic infections associated with the ectopic corticotropin syndrome.","volume":"149","author":"Sieber","year":"1989","journal-title":"Arch Intern Med"},{"key":"2020071617480807600_R35","first-page":"512","article-title":"Pneumocystis carinii pneumonia complicating somatostatin therapy of Cushing\u2019s syndrome in a patient with metastatic pancreatic islet cell carcinoma and Zollinger-Ellison syndrome.","volume":"86","author":"McQuillen","year":"1991","journal-title":"Am J Gastroenterol"},{"key":"2020071617480807600_R36","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1001\/jama.1992.03480060078034","article-title":"Pneumocystis carinii pneumonia among patients without AIDS at a cancer hospital.","volume":"267","author":"Sepkowitz","year":"1992","journal-title":"JAMA"},{"key":"2020071617480807600_R37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4065\/71.1.5","article-title":"Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illnesses and prior corticosteroid therapy.","volume":"71","author":"Yale","year":"1996","journal-title":"Mayo Clin Proc"},{"key":"2020071617480807600_R38","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF03350337","article-title":"Cushing\u2019s syndrome complicated by multiple opportunistic infections.","volume":"21","author":"Bakker","year":"1998","journal-title":"J Endocrinol Invest"},{"key":"2020071617480807600_R39","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/0002-9343(89)90458-0","article-title":"Q fever endocarditis: delay in diagnosis due to an apparent clinical response to corticosteroids.","volume":"86","author":"Shafer","year":"1989","journal-title":"Am J Med"},{"key":"2020071617480807600_R40","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S0031-3955(16)36514-2","article-title":"Infectious complications in childhood acute leukemias.","volume":"35","author":"Albano","year":"1988","journal-title":"Pediatr Clin North Am"},{"key":"2020071617480807600_R41","first-page":"512","article-title":"Pneumocystis carinii pneumonia complicating somatostatin therapy of Cushing\u2019s syndrome in a patient with metastatic pancreatic islet cell carcinoma and Zollinger-Ellison syndrome.","volume":"86","author":"McQuillen","year":"1991","journal-title":"Am J Gastroenterol"},{"key":"2020071617480807600_R42","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/0140-6736(93)90858-E","article-title":"Pneumocystis carinii pneumonia after transsphenoidal removal of microadenoma causing Cushing\u2019s syndrome (Letter).","volume":"341","author":"Russi","year":"1993","journal-title":"Lancet"},{"key":"2020071617480807600_R43","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1056\/NEJM199405053301809","article-title":"Clinical problem-solving. Half a loaf.","volume":"330","year":"1994","journal-title":"N Engl J Med"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/85\/1\/42\/9175567\/jcem0042.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/85\/1\/42\/9175567\/jcem0042.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T03:39:24Z","timestamp":1594957164000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/85\/1\/42\/2851344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,1,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2000,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jcem.85.1.6294","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,1,1]]}}}