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. 2021 Nov 29;43(5):852–877. doi: 10.1210/endrev/bnab046

Table 4.

Caveats and restrictions for tests used to screen for hypercortisolism

Test Caveat When can the test be used despite the caveat? Verifying the result
All tests May be falsely normal in a patient with mild or cyclic CS If the pretest probability is high based on history and physical examination, repeat testing at intervals or when patient feels worst. Review caveats for each test
UFC May be falsely increased with fluid intake > 4 L/d (106) If subjects reduce intake Measure volume; if volume is high, ask about intake
May be falsely increased or decreased with incorrect collection Measure creatinine, which should be ±15% from day to day; check volume
Will be decreased in the setting of renal impairment (107) Use with caution when GFR is 30-50 mL/min Only use result if value is elevated
May be falsely increased with high sodium intake (108,109) Impact is not clear, as normal ranges may reflect sodium intake; advise patient to reduce sodium when collecting
May be increased in pseudo-CS (110) Values > 3-fold upper normal limit are more likely to be true CS
1 mg DST May be falsely normal in Cushing’s disease patients, presumably because of slow drug metabolism (111) Measure dexamethasone; if in range expected of an 8 mg dose, consider Cushing’s disease
May be falsely abnormal in patients with elevated CBG (2o oral estrogen) or in those with fast metabolism of dexamethasone (112) Fewest false-positive results in patients not taking medications that interact with CYP3A4 (113) Measure dexamethasone level—if low, increase dose to achieve correct level; measure CBG—if high, discontinue estrogen for 4-6 weeks
May be falsely abnormal in renal failure (114)
Bedtime salivary cortisol May be falsely abnormal in older men and women, and in hypertensive or diabetic patients (115) If used in these populations, consider accepting only normal results.
May be falsely abnormal in individuals with variable sleeping times (eg, shift workers) (116) If used in this population, consider accepting only normal results.

Abbreviations: CBG, corticosteroid-binding globulin; CS, Cushing’s syndrome; 1 mg DST, 1 mg overnight dexamethasone suppression test; salF, salivary cortisol; GFR, glomerular filtration rate; UFC, urinary free cortisol.