Table 6.
Summary of published data on diagnostic screening tests for investigating autonomous cortisol secretion and Cushing’s syndrome in patients with adrenal incidentaloma.
| CS | ACS or mild CS or occult CS | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Test | Cut-off | Sensitivity (%) | Specificity (%) | False positive (%) | False negative (%) | Ref. | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | Ref. |
| 1-mg DST | 1.8 µg/dL (50 nmol/L) | 95-100 | 60-80.2 | 8 | 0 | (225,226) | 75-100 | 62–72 | 59 | 100 | (64,68,227-231) |
| 2.0 µg/dL | 91.3 | 56.3 | (68,230,231) | ||||||||
| 2.2 µg/dL | 100 | 67 | (230,231) | ||||||||
| 3 µg/dL (86 nmol/L) | 100 | 91.8 | (226) | 52.4-86.4 | 52.4-96.3 | (230,231) | |||||
| 5 µg/dL (138 nmol/L) | 86.5 | 92-97.4 | 3 | 12-15 | (225) | 44–83.3 | 83-100 | 57 | 95 | (64,68,227,228,230,231) | |
| LNSC | 2.7 nmol/L (RIA) | 97 | 77 | (232) | |||||||
| 2.8 nmol/L (LC-MS/MS) | 31.3 | 83.3 | (233) | ||||||||
| 100 ng/dL (2.76 nmol/L) LC-MS/MS | 93 | 91 | (234) | 93 | 91 | (234) | |||||
| 0.350 μg/dL | 93.8 | 79.5 | (227) | ||||||||
| 3.6 nmol/L (RIA) | 92 | 100 | (232) | ||||||||
| 5.1 nmol/L | 100 | 100 | (226) | 22.7 | 87.7 | (235) | |||||
| 14.46 nmol/L | 86 (73–93) | 92 (86–95) | (228) | ||||||||
| 24-h UFC | 80 µg (170 nmol) or ULN | 91-96 | 89.6-92.5 | 8 | 2 | (225, 226) | 31.8-76 | 80-100 | 49 (100) | 96 (93.3) | (227,228) |
| DHEA-S ratio | 1.2 | 100 | 91.1 | (236) | |||||||
| ACTH | 41-86.4 | 38-96 | 47 | 96 | (64,230) | ||||||
| Midnight serum cortisol | 1.8 µg/dL (50 nmol/L) | 99-100 | 20.2 | (225) | 22.7 | 87.7 | (64) | ||||
| 5 µg/dL (135 nmol/L) | 95-100 | 73.9 | (225) | 77 | 68 | ||||||
| 7.5 µg/dL | 90-96 | 87.7 | (225) | ||||||||
| Plasma steroid metabolomic | Sensitivity 97 AUC 0.991 | (237) | |||||||||
| Combination of tests | |||||||||||
| 24-hour UFC + LNSC | >70 µg UFC + LNSC > 5.4 µg/dL (149 nmol/L) | 30.8 | 100 | ||||||||
| 1-mg DST and 24-hour UFC and ACTH <10 pg/mL | >70 µg UFC + LNSC >3 µg/dL (86 nmol/L) | 55.6-65.2 | 68.8-82.9 | (230) | |||||||
| 1-mg DST + Dexamethasone level > 3.3 nmol/L | Serum cortisol 1.8 µg/dL (50 nmol/L) | 100 | 84 | (238) | |||||||
| 1-mg DST + Dexamethasone level > 3.3 nmol/L | Salivary cortisol 0.55 nmol/L | 71 | 90 | (238) | |||||||
| 1-mg DST + dexamethasone level >3.3 nmol/L | Salivary cortisone 2.7 nmol/L | 91 | 82 | (238) | |||||||
| 1 mg DST + LNSC (LC-MS/MS) | Serum cortisol 1.8 µg/dL (50 nmol/L), LNSC 1.4 nmol/L | 88.9 | 85.2 | (233) | |||||||
Abbreviations: CS, Cushing’s syndrome; ACS, autonomous cortisol secretion; LRneg, negative likelihood ratio; LRpos, positive likelihood ratio; CI, confidence interval; 1-mg dexamethasone suppression test (DST); LNSC, late night salivary cortisol; PPV, positive predictive value [TP/(TP + FP)]; negative NPV, negative predictive value [TN/(TN + FN)]; DHEAS ratio calculated by dividing the measured DHEAS by the lower limit of the reference range (age and sex matched); ULN, upper limit of normal.
*Consider pseudo-CS state: alcoholism, psychiatric disorders, stress, diabetes, obesity, vigorous exercise, pain, hypothalamic amenorrhea, pregnancy.