A Single Midnight Serum Cortisol Measurement Distinguishes Cushing’s Syndrome from Pseudo-Cushing States1
Dimitris A. Papanicolaou,
Jack A. Yanovski,
Gordon B. Cutler, Jr.2,
George P. Chrousos and
Lynnette K. Nieman
Developmental Endocrinology Branch, National Institute of Child
Health and Human Development, National Institutes of Health, Bethesda,
Maryland 20892
Address all correspondence and requests for reprints to: Dimitris A. Papanicolaou, M.D., Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive, MSC 1862, Bethesda, Maryland 20892-1862. E-mail: papanicd{at}cc1.nichd.nih.gov
Abstract
Cushing’s syndrome (CS) may be difficult to distinguishfrom
pseudo-Cushing states (PCS) based on physical findingsor urinary
glucocorticoid excretion. As the lack of diurnalvariation in serum
cortisol is characteristic of CS, we studiedwhether diurnal cortisol
determinations could discriminate CSfrom PCS. Two hundred and
sixty-three patients were evaluated:240 had CS, and 23 had PCS. Urine
was collected for 24 h formeasurement of cortisol and
17-hydroxycorticosteroids (17OHCS).Blood was drawn at 2300, 2330,
0000, 0030, and 0100 h and at0600, 0630, 0700, 0730, and
0800 h the next morning for serumcortisol determination. The main
outcome measure was the sensitivityof these parameters for the
diagnosis of CS at 100% specificity.A midnight cortisol value greater
than 7.5 µg/dL correctlyidentified 225 of 234 patients with CS and
all PCS patients.This sensitivity (96%) was superior to that obtained
for anyother measure, including urinary cortisol (45%), 17OHCS
(22%),any other individual cortisol time point (10–92%), the
morning(23%) or the evening (93%) cortisol mean, and the ratio
(11%)of morning to evening values. We conclude that at 100%
specificity,a single serum cortisol value above 7.5 µg/dL at
midnightdiscriminates CS from PCS with higher sensitivity than 24-h
urinarycortisol or 17OHCS, or other individual or combined measuresof
serum cortisol.
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