Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome.
OBJECTIVE
Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS.


METHODS
Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined.


RESULTS
AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS.


CONCLUSIONS
According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.
Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain.|Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.
G
G
Aranda
Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.
M
M
Careaga
Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain.|Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.|Centro de Investigación en Red, CIBERDEM, Barcelona, Spain.|University of Barcelona, Barcelona, Spain.
F A
FA
Hanzu
Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.
I
I
Patrascioiu
Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.
P
P
Ríos
Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain.|Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.|Centro de Investigación en Red, CIBERDEM, Barcelona, Spain.|University of Barcelona, Barcelona, Spain.
M
M
Mora
Biochemistry and Molecular Genetics Service, Hospital Clinic Universitari, IDIBAPS, CIBERehd, Villarroel 170, 08036, Barcelona, Spain.
B
B
Morales-Romero
Biochemistry and Molecular Genetics Service, Hospital Clinic Universitari, IDIBAPS, CIBERehd, Villarroel 170, 08036, Barcelona, Spain.|Biomedicine Department, University of Barcelona, Barcelona, Spain.
W
W
Jiménez
Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain.|Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.|Centro de Investigación en Red, CIBERDEM, Barcelona, Spain.|University of Barcelona, Barcelona, Spain.
I
I
Halperin
Biochemistry and Molecular Genetics Service, Hospital Clinic Universitari, IDIBAPS, CIBERehd, Villarroel 170, 08036, Barcelona, Spain. casals@clinic.cat.
G
G
Casals
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000175:diagnosis* / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D007118:Immunoassay / Q000706:statistics & numerical data*; D008297:Male; D013058:Mass Spectrometry / Q000706:statistics & numerical data*; D008875:Middle Aged
D006854:Hydrocortisone
Cushing’s syndrome; Immunoassay; Mass spectrometry; Urinary free cortisol