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. 2021 Apr 22;12:658429. doi: 10.3389/fendo.2021.658429

Table 1.

Diagnostic procedures commonly used in evaluation of hypercortisolemia.

Diagnostic procedure Clinical use Cutoff values
First- and second-line screening tests for hypercortisolemia
24-h UFC Suspicion of hypercortisolemia – screening test Depends on laboratory
and assay method
Low-dose overnight DST Suspicion of hypercortisolemia – screening test <50 nmol/l (1,8 µg/dl)
in healthy subjects
Late-night salivary cortisol Suspicion of hypercortisolemia – screening test Cut-off values vary depending
on population and assay method (20, 2224)
Two-day LDDST Suspicion of hypercortisolemia – screening test <50 nmol/l (1,8 µg/dl)
in healthy subjects
Late-night serum cortisol Suspicion of hypercortisolemia <50 nmol/l (1,8 µg/dl)
in sleeping healthy subjects
Two-day LDDST
with consecutive CRH test
Suspicion of hypercortisolemia, useful in non-neoplastic hypercortisolemia Serum cortisol stays suppressed <38 nmol/l (1,4 µg/dl) after CRH administration
in healthy subjects and non-neoplastic hypercortisolemia
DDAVP stimulation test Suspicion of ACTH-dependent hypercortisolemia, useful in cyclic hypercortisolemia,
useful in distinguishing between neoplastic and non-neoplastic hypercortisolemia (25)
Increase of plasma ACTH
by at least 50% in ACTH-dependent cases
Hair cortisol Suspicion of hypercortisolemia, useful
in cyclic hypercortisolemia
Depends on laboratory
and assay method
Evaluation of origin of hypercortisolemia
Morning plasma ACTH Evaluation of origin
of hypercortisolemia (ACTH-dependent vs. ACTH-independent)
>20 pg/ml in ACTH-dependent cases
<10 pg/ml in ACTH-independent cases
CRH stimulation test Evaluation of origin of ACTH-dependent hypercortisolemia,
useful in distinguishing between ACTH-dependent and ACTH-independent neoplastic hypercortisolemia when ACTH is indeterminate (10-20 pg/ml) (26)
Increase of plasma ACTH
by 35-50% or serum cortisol
by 14-20% in ACTH-dependent cases of pituitary origin
Two-day HDDST Evaluation of origin of ACTH-dependent hypercortisolemia, however its use remains controversial Drop of serum cortisol
by at least 50%
in corticotropinoma

DST, dexamethasone suppression test; LDDST, low-dose dexamethasone suppression test; HDDST, high-dose dexamethasone suppression test; ACTH, corticotropin; CRH, corticoliberin; DDAVP, desmopressin; UFC, urinary free cortisol.