Endocrinol Metab.  2015 Sep;30(3):297-304. 10.3803/EnM.2015.30.3.297.

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease

• Hong AR
• Kim JH
• Hong ES
• Kim IK
• Park KS
• Ahn CH
• Kim SW
• Shin CS
• Kim SY

• KMID: 2407080
• DOI: http://doi.org/10.3803/EnM.2015.30.3.297

Abstract

BACKGROUND
Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level.
METHODS
We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured.
RESULTS
Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively.
CONCLUSION
Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

Keyword

Adrenal Cushing syndrome; Cushing disease; Adrenocorticotropic hormone; High-dose dexamethasone suppression test; Dehydroepiandrosterone sulfate

MeSH Terms

Adrenocorticotropic Hormone*
Cushing Syndrome*
Dehydroepiandrosterone Sulfate
Dexamethasone
Diagnosis, Differential
Diagnostic Tests, Routine
Humans
Hydrocortisone
Pituitary ACTH Hypersecretion*
Plasma*
Retrospective Studies
Sensitivity and Specificity
Adrenocorticotropic Hormone
Dehydroepiandrosterone Sulfate
Dexamethasone
Hydrocortisone

Figure

• 

  Fig. 1 (A) Plasma adrenocorticotropic hormone (ACTH) and (B) serum dehydroepiandrosterone sulfate (DHEA-S) levels. Percentage suppression of (C) serum cortisol and (D) urine free cortisol (UFC) after high-dose dexamethasone suppression test in patients with Cushing disease (CD) and adrenal Cushing syndrome (CS).

• 

  Fig. 2 Receiver operating characteristic (ROC) curves for plasma adrenocorticotropic hormone (ACTH), serum dehydroepiandrosterone sulfate (DHEA-S), percentage suppression of serum cortisol, and urine free cortisol (UFC) after the high-dose dexamethasone suppression test. The black line represents the results equivalent to chance.

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