Table 5.
Summary of published guidelines for the diagnosis of subclinical Cushing’s syndrome (SCS)/autonomous cortisol secretion (ACS) in patients with AI.
| Guideline (year) (ref.) | NIH (2003) (221) | Endocrine Society (2008) (212) | AACE/AAES (2009) (86) | FSE (2008) (7) | IACE (2011) (222) | ESE/ENSAT (2016) (4) | Korea (2017) (223) | JES (2018) (224) |
|---|---|---|---|---|---|---|---|---|
| Terminology | SCS | SCS | ACS | Asymptomatic hypercortisolism | SCS | |||
| Country | USA | USA | USA | France | Italy | Europe | Korea | Japan |
| First screening test (cut-off) | ||||||||
| 1-mg DST cut-off point | Yes >5 μg/dL: possible SCS | Yes >1.8 μg/dL | Yes >5 μg/dL | Yes >1.8 µg/dL | Yes <1.8 μg/dL: exclude >5.0 μg/dL: consider 1.8–5.0 μg/dL: indeterminate | Yes <1.8 μg/dL: exclude >5.0 μg/dL: ACS 1.8–5.0 μg/dL: possible ACS | Yes <1.8 μg/dL: normal >5.0 μg/dL: asymptomatic hypercortisolism 1.8–5.0 μg/dL: additional testing | Yes >5.0 μg/dL ≥3 μg/dL with (any of A-D) or E ≥1.8 μg/dL with (A and B) or E |
| Late night salivary cortisol | NM | Yes (> 145 ng/dL) | NR | NR | NR | NR | NM | NR |
| Second screening test | ||||||||
| 24-hour UFC | NM | NR | NR | Yes | Yes | Yes (if 1mg DST > 5ug/dL) | Not recommended | |
| Late-night serum cortisol | NM | NM | NM | Yes | Yes | NM | NM | Serum 21.00-24.00 ≥5 μg/dL |
| ACTH | Yes | |||||||
| Late-night salivary cortisol | NM | NM | NR | NM | NR | Yes (if 1mg DST > 5ug/dL) | NM | |
| 4-mg DST | NM | NM | NM | NM | NR | Yes (if 1mg DST > 5ug/dL) | NR | |
| Confirmatory test | ||||||||
| 4-mg DST | NM | NR | Yes | NM | NR | NM | NR | |
| 8-mg DST | NM | NR | NM | NR | NM | NR | ||
| Localization (adrenal in origin) | ||||||||
| ACTH | NM | Yes | Yes | Yes | Yes | Yes | <10 pg/mL | |
| DHEA-S | NM | Yes | Yes | NR | NR | NM | NM | |
| 4-mg DST | NM | NM | NM | NM | NM | |||
| 8-mg DST | NM | NM | NM | NM | NM | |||
| Adrenal scintigraphy | NR | NM | NM | Yes | NR | NM | NM |
Abbreviations: NIH, National Institutes of Health; ES, Endocrine Society; AACE/AAES, American Association of Clinical Endocrinologists/American Association of Endocrine Surgeons; FSE, French Society of Endocrinology; IACE, Italian Association of Clinical Endocrinologists; DST, dexamethasone suppression test; ACTH, adrenocorticotrophic hormone; DHEAS, DHEA sulfate; NM, not mentioned; NR, not recommended; JES, Japan Endocrine Society; UFC, urine free cortisol.
JES abbreviations: A, low plasma levels of ACTH in the early morning; B, no diurnal changes in serum cortisol levels; C, unilateral uptake on adrenal scintigraphy; D, low serum levels of DHEA-S; E, transient adrenal insufficiency or atrophy of the attached normal adrenal cortex after removal of the adrenal tumor.
Adapted from reference (224).