Screening Tests for Cushing's Syndrome: Urinary Free Cortisol Role Measured by LC-MS/MS.
OBJECTIVE
As initial screening for Cushing's syndrome (CS), The Endocrine Society guidelines recommend one of the following: the 1-mg dexamethasone suppression test (DST) or late-night salivary cortisol (LNSC) or urinary free cortisol (UFC) measurement. We examined the diagnostic performance of the above-mentioned tests in a series of patients.


METHODS
We retrospectively analyzed 137 patients with clinical conditions suggestive of hypercortisolism: 38 with confirmed CS diagnosis and 99 without (termed non-CS). UFC was measured by liquid chromatography tandem-mass spectrometry, whereas LNSC by the radioimmunometric method and serum cortisol were measured by a chemiluminescence immunoassay.


RESULTS
Comparing CS vs non-CS, a cutoff of 138 nmol/L after 1-mg DST revealed the best specificity (SP; 97%), whereas the 50-nmol/L cutoff confirmed the best sensitivity (SE; 100%); the SE and SP for LNSC greater than 14.46 nmol/L were, respectively, 84% and 89%, whereas the SE and SP for UFC greater than 170 nmol per 24 hours, they were 97% and 91%. Overall, UFC revealed both a combined higher positive and a lower negative likelihood ratio among first-line tests (respectively 10.7 and 0.03). Computing a receiver-operating curve -contrast analysis to compare the power of each single test with that of the others, alone or combined (DST+LNSC, DST+UFC, and LNSC+UFC) or with that of all the tests together (DST+LNSC+UFC), the UFC assay was at least as good as all the other possible combinations.


CONCLUSIONS
Measuring UFC by liquid chromatography tandem-mass spectrometry achieves the best accuracy in diagnosing CS among patients presenting with suspected hypercortisolism.
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Filippo
F
Ceccato
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Mattia
M
Barbot
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Marialuisa
M
Zilio
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Anna Chiara
AC
Frigo
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Nora
N
Albiger
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Valentina
V
Camozzi
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Giorgia
G
Antonelli
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Mario
M
Plebani
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Franco
F
Mantero
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Marco
M
Boscaro
Endocrinology Unit (F.C., M.Ba., M.Z., N.A., V.C., F.M., M.Bo., C.S.) and Laboratory Medicine Unit (G.A., M.P.), Department of Medicine, and Unit of Biostatistics, Epidemiology, and Public Health (A.C.F.), Department of Cardiac, Thoracic, and Vascular Sciences, University-Hospital of Padova, 35128 Padova, Italy.
Carla
C
Scaroni
D000304:Adrenal Cortex Function Tests; D000328:Adult; D002853:Chromatography, Liquid; D003480:Cushing Syndrome / Q000175:diagnosis* / Q000652:urine; D003907:Dexamethasone; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000652:urine*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012463:Saliva / Q000737:chemistry; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D003907:Dexamethasone; D006854:Hydrocortisone