| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Articles |
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
Cushings syndrome (CS) may be difficult to distinguish from pseudo-Cushing states (PCS) based on physical findings or urinary glucocorticoid excretion. As the lack of diurnal variation in serum cortisol is characteristic of CS, we studied whether diurnal cortisol determinations could discriminate CS from PCS. Two hundred and sixty-three patients were evaluated: 240 had CS, and 23 had PCS. Urine was collected for 24 h for measurement of cortisol and 17-hydroxycorticosteroids (17OHCS). Blood was drawn at 2300, 2330, 0000, 0030, and 0100 h and at 0600, 0630, 0700, 0730, and 0800 h the next morning for serum cortisol determination. The main outcome measure was the sensitivity of these parameters for the diagnosis of CS at 100% specificity. A midnight cortisol value greater than 7.5 µg/dL correctly identified 225 of 234 patients with CS and all PCS patients. This sensitivity (96%) was superior to that obtained for any other measure, including urinary cortisol (45%), 17OHCS (22%), any other individual cortisol time point (1092%), 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 midnight discriminates CS from PCS with higher sensitivity than 24-h urinary cortisol or 17OHCS, or other individual or combined measures of serum cortisol.
This article has been cited by other articles:
![]() |
T. Deutschbein, N. Unger, J. Hinrichs, M. K Walz, K. Mann, and S. Petersenn Late-night and low-dose dexamethasone-suppressed cortisol in saliva and serum for the diagnosis of cortisol-secreting adrenal adenomas Eur. J. Endocrinol., November 1, 2009; 161(5): 747 - 753. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Raff Utility of Salivary Cortisol Measurements in Cushing's Syndrome and Adrenal Insufficiency J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 3647 - 3655. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-P. Hsiao, L. S. Kirschner, I. Bourdeau, M. F. Keil, S. A. Boikos, S. Verma, A. J. Robinson-White, M. Nesterova, A. Lacroix, and C. A. Stratakis Clinical and Genetic Heterogeneity, Overlap with Other Tumor Syndromes, and Atypical Glucocorticoid Hormone Secretion in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Compared with Other Adrenocortical Tumors J. Clin. Endocrinol. Metab., August 1, 2009; 94(8): 2930 - 2937. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Arnaldi, G. Tirabassi, R. Papa, G. Furlani, L. Trementino, M. Cardinaletti, E. Faloia, and M. Boscaro Human corticotropin releasing hormone test performance in the differential diagnosis between Cushing's disease and pseudo-Cushing state is enhanced by combined ACTH and cortisol analysis Eur. J. Endocrinol., June 1, 2009; 160(6): 891 - 898. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Q. Purnell, S. E. Kahn, M. H. Samuels, D. Brandon, D. L. Loriaux, and J. D. Brunzell Enhanced cortisol production rates, free cortisol, and 11{beta}-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E351 - E357. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A. Carrasco, J. Coste, L. Guignat, L. Groussin, M. A. Dugue, S. Gaillard, X. Bertagna, and J. Bertherat Midnight Salivary Cortisol Determination for Assessing the Outcome of Transsphenoidal Surgery in Cushing's Disease J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4728 - 4734. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Batista, N. Courcoutsakis, J. Riar, M. F. Keil, and C. A. Stratakis Severe Obesity Confounds the Interpretation of Low-Dose Dexamethasone Test Combined with the Administration of Ovine Corticotrophin-Releasing Hormone in Childhood Cushing Syndrome J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4323 - 4330. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. K. Nieman, B. M. K. Biller, J. W. Findling, J. Newell-Price, M. O. Savage, P. M. Stewart, and V. M. Montori The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1526 - 1540. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. B. Elamin, M. H. Murad, R. Mullan, D. Erickson, K. Harris, S. Nadeem, R. Ennis, P. J. Erwin, and V. M. Montori Accuracy of Diagnostic Tests for Cushing's Syndrome: A Systematic Review and Metaanalyses J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1553 - 1562. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kidambi, H. Raff, and J. W Findling Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome Eur. J. Endocrinol., December 1, 2007; 157(6): 725 - 731. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Gatta, O. Chabre, C. Cortet, M. Martinie, J.-B. Corcuff, P. Roger, and A. Tabarin Reevaluation of the Combined Dexamethasone Suppression-Corticotropin-Releasing Hormone Test for Differentiation of Mild Cushing's Disease from Pseudo-Cushing's Syndrome J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4290 - 4293. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Pecori Giraldi, A. G. Ambrogio, M. De Martin, L. M. Fatti, M. Scacchi, and F. Cavagnini Specificity of First-Line Tests for the Diagnosis of Cushing's Syndrome: Assessment in a Large Series J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4123 - 4129. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Chiodini, M. L. Mascia, S. Muscarella, C. Battista, S. Minisola, M. Arosio, S. A. Santini, G. Guglielmi, V. Carnevale, and A. Scillitani Subclinical Hypercortisolism among Outpatients Referred for Osteoporosis Ann Intern Med, October 16, 2007; 147(8): 541 - 548. [Abstract] [Full Text] [PDF] |
||||
![]() |
J R Meinardi, B H R Wolffenbuttel, and R P F Dullaart Cyclic Cushing's syndrome: a clinical challenge Eur. J. Endocrinol., September 1, 2007; 157(3): 245 - 254. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Batista, J. Riar, M. Keil, and C. A. Stratakis Diagnostic Tests for Children Who Are Referred for the Investigation of Cushing Syndrome Pediatrics, September 1, 2007; 120(3): e575 - e586. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Nieman The Dexamethasone-Suppressed Corticotropin-Releasing Hormone Test for the Diagnosis of Cushing's Syndrome: What Have We Learned in 14 Years? J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2876 - 2878. [Full Text] [PDF] |
||||
![]() |
J. W. Findling and H. Raff Cushing's Syndrome: Important Issues in Diagnosis and Management J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3746 - 3753. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Reimondo, B. Allasino, S. Bovio, P. Paccotti, A. Angeli, and M. Terzolo Evaluation of the effectiveness of midnight serum cortisol in the diagnostic procedures for Cushing's syndrome Eur. J. Endocrinol., December 1, 2005; 153(6): 803 - 809. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Viardot, P. Huber, J. J. Puder, H. Zulewski, U. Keller, and B. Muller Reproducibility of Nighttime Salivary Cortisol and Its Use in the Diagnosis of Hypercortisolism Compared with Urinary Free Cortisol and Overnight Dexamethasone Suppression Test J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5730 - 5736. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Terzolo, S. Bovio, A. Pia, P. A. Conton, G. Reimondo, C. Dall'Asta, D. Bemporad, A. Angeli, G. Opocher, M. Mannelli, et al. Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma Eur. J. Endocrinol., August 1, 2005; 153(2): 307 - 315. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Matyakhina, R. J. Freedman, I. Bourdeau, M.-H. Wei, S. G. Stergiopoulos, A. Chidakel, M. Walther, M. Abu-Asab, M. Tsokos, M. Keil, et al. Hereditary Leiomyomatosis Associated with Bilateral, Massive, Macronodular Adrenocortical Disease and Atypical Cushing Syndrome: A Clinical and Molecular Genetic Investigation J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3773 - 3779. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C W Ma, W. B. Chan, W. Y. So, P. C Y Tong, J. C N Chan, and C. C. Chow Carbamazepine and false positive dexamethasone suppression tests for Cushing's syndrome BMJ, February 5, 2005; 330(7486): 299 - 300. [Full Text] [PDF] |
||||
![]() |
M. Terzolo, B. Allasino, S. Bosio, E. Brusa, F. Daffara, M. Ventura, E. Aroasio, G. Sacchetto, G. Reimondo, A. Angeli, et al. Hyperhomocysteinemia in Patients with Cushing's Syndrome J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3745 - 3751. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Ilias, R. Chang, K. Pacak, E. H. Oldfield, R. Wesley, J. Doppman, and L. K. Nieman Jugular Venous Sampling: An Alternative to Petrosal Sinus Sampling for the Diagnostic Evaluation of Adrenocorticotropic Hormone-Dependent Cushing's Syndrome J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3795 - 3800. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. F. Gunther, I. Bourdeau, L. Matyakhina, D. Cassarino, D. E. Kleiner, K. Griffin, N. Courkoutsakis, M. Abu-Asab, M. Tsokos, M. Keil, et al. Cyclical Cushing Syndrome Presenting in Infancy: An Early Form of Primary Pigmented Nodular Adrenocortical Disease, or a New Entity? J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3173 - 3182. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Yaneva, H. Mosnier-Pudar, M.-A. Dugue, S. Grabar, Y. Fulla, and X. Bertagna Midnight Salivary Cortisol for the Initial Diagnosis of Cushing's Syndrome of Various Causes J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3345 - 3351. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Arnaldi, A. Angeli, A. B. Atkinson, X. Bertagna, F. Cavagnini, G. P. Chrousos, G. A. Fava, J. W. Findling, R. C. Gaillard, A. B. Grossman, et al. Diagnosis and Complications of Cushing's Syndrome: A Consensus Statement J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5593 - 5602. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Putignano, P. Toja, A. Dubini, F. P. Giraldi, S. M. Corsello, and F. Cavagnini Midnight Salivary Cortisol Versus Urinary Free and Midnight Serum Cortisol as Screening Tests for Cushing's Syndrome J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4153 - 4157. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Raff and J. W. Findling A Physiologic Approach to Diagnosis of the Cushing Syndrome Ann Intern Med, June 17, 2003; 138(12): 980 - 991. [Full Text] [PDF] |
||||
![]() |
D. A. Papanicolaou, N. Mullen, I. Kyrou, and L. K. Nieman Nighttime Salivary Cortisol: A Useful Test for the Diagnosis of Cushing's Syndrome J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4515 - 4521. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Terzolo, A. Pia, A. Ali, G. Osella, G. Reimondo, S. Bovio, F. Daffara, M. Procopio, P. Paccotti, G. Borretta, et al. Adrenal Incidentaloma: A New Cause of the Metabolic Syndrome? J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 998 - 1003. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Boscaro, L. Barzon, and N. Sonino The Diagnosis of Cushing's Syndrome: Atypical Presentations and Laboratory Shortcomings Arch Intern Med, November 13, 2000; 160(20): 3045 - 3053. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Moro, P. Putignano, M. Losa, C. Invitti, C. Maraschini, and F. Cavagnini The Desmopressin Test in the Differential Diagnosis between Cushing's Disease and Pseudo-Cushing States J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3569 - 3574. [Abstract] [Full Text] |
||||
![]() |
M. H. Samuels, D. D. Brandon, L. M. Isabelle, D. M. Cook, K. E. Graham, J. Q. Purnell, and D. L. Loriaux Cortisol Production Rates in Subjects with Suspected Cushing's Syndrome: Assessment by Stable Isotope Dilution Methodology and Comparison to Other Diagnostic Methods J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 22 - 28. [Abstract] [Full Text] |
||||
![]() |
C. A. Stratakis, N. Sarlis, L. S. Kirschner, J. A. Carney, J. L. Doppman, L. K. Nieman, G. P. Chrousos, and D. A. Papanicolaou Paradoxical Response to Dexamethasone in the Diagnosis of Primary Pigmented Nodular Adrenocortical Disease Ann Intern Med, October 19, 1999; 131(8): 585 - 591. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. E. Graham, M. H. Samuels, G. M. Nesbit, D. M. Cook, O. R. ONeill, S. L. Barnwell, and D. L. Loriaux Cavernous Sinus Sampling Is Highly Accurate in Distinguishing Cushing's Disease from the Ectopic Adrenocorticotropin Syndrome and in Predicting Intrapituitary Tumor Location J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1602 - 1610. [Abstract] [Full Text] |
||||
![]() |
M. Castro, P. C. L. Elias, A. R. P. Quidute, F. P. B. Halah, and A. C. Moreira Out-Patient Screening for Cushing's Syndrome: The Sensitivity of the Combination of Circadian Rhythm and Overnight Dexamethasone Suppression Salivary Cortisol Tests J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 878 - 882. [Abstract] [Full Text] |
||||
![]() |
T. C. Friedman and D. A. Papanicolaou Comment on High Urinary Free Cortisol Excretion in a Patient with Psychogenic Polydipsia J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3378a - 3378. [Full Text] |
||||
![]() |
H. Raff, J. L. Raff, and J. W. Findling Late-Night Salivary Cortisol as a Screening Test for Cushing's Syndrome J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2681 - 2686. [Abstract] [Full Text] |
||||
![]() |
A Better Screening Test for Cushing's Syndrome? Journal Watch (General), April 14, 1998; 1998(414): 8 - 8. [Full Text] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |