Usefulness of cortisol/ACTH ratio (CAR) for diagnosis of cushing's syndrome: comparison of CAR with findings in dexamethasone suppression test

Abstract

Cushing's syndrome and subclinical Cushing's syndrome (SCS) are conditions of increased cortisol secretion from the adrenal glands. Cushing's syndrome includes adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (Cushing's disease) and ACTH-independent Cushing's syndrome (AICS). The purpose of this study was to investigate the diagnostic potential of the cortisol / adrenocorticotropic hormone (ACTH) ratio (CAR) for diagnosis of Cushing's syndrome or SCS in adult subjects. This was a single-center, retrospective, observational study. This study enrolled 44 subjects with SCS, 14 AICS, 10 CD, and 248 non-Cushing's syndrome subjects who had undergone a 1 mg dexamethasone suppression test (1 mg DST). Definition of SCS was as follows: no physical signs characteristic of Cushing syndrome and cortisol was ≥ 83 nmol/L in 1 mg DST. The diagnostic potential of CAR for diagnosis of Cushing's syndrome was evaluated by comparing the correlation between CAR and after-load cortisol level in 1 mg DST. As the results, there was a strong positive correlation between CAR and after-load cortisol level in subjects with AICS (r = 0.800, p < 0.005). CAR was 10,040 ± 4170 nmol/pmol in subjects with NCS, 17,535 ± 10,246 nmol/pmol in SCS, 101,221 ± 18,009 nmol/pmol in AICS, and 4324 ± 2051 nmol/pmol in CD, all of which were significantly higher compared to those with AICS (p < 0.0005). The cutoff values of CAR for screening at our institution were 11,849.6 nmol/pmol for AICS (AUC 0.935, p < 0.005, sensitivity 92.3%, specificity 83.5%) and 7006.1 nmol/pmol for CD (AUC 0.714, p < 0.05, sensitivity 100.0%, specificity 46.8%). There was a positive correlation between CAR and adrenal adenoma diameter in subjects with AICS (r = 0.508, p < 0.05), but there was no correlation between tumor diameter and CAR in subjects with SCS and CD. In conclusion, high CAR indicates increased cortisol secretion from the adrenal glands. Since CAR is a simple indicator that can be easily evaluated by general practitioners as well as endocrinologists, we think CAR would be useful for the early detection of Cushing's syndrome.

Psychological stress, cortisol, ACTH, and cortisol/ACTH ratio associated with burning mouth syndrome

“…However, in this study, ACTH itself was not correlated with the presence of psychological stress in patients with BMS, and only the cortisol/ACTH ratio showed a positive correlation. Cortisol/ACTH ratio is useful to diagnosis of Cushing's syndrome and primary hypoadrenocorticism [17,27]. Further research is needed to determine the signi cance of cortisol and cortisol/DHEA as biomarkers of BMS.…”

“…This hormone stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland, which triggers the release of cortisol from the adrenal cortex [16]. A high Cortisol/ACTH ratio in Cushing's syndrome indicates increased cortisol secretion from the adrenal glands and has been proposed as a biomarker for the diagnosis of the disease [17,18].…”

Effects of self-perceived psychological stress on clinical symptoms, cortisol, and cortisol/ACTH ratio in patients with burning mouth syndrome

“…However, in this study, ACTH did not correlate with psychological stress in patients with BMS; only the cortisol/ACTH ratio showed a positive correlation. The cortisol/ACTH ratio is useful for diagnosing Cushing syndrome and primary hypoadrenocorticism [ 24 , 36 ]. Further research is needed to determine the significance of cortisol and the cortisol/DHEA ratio as BMS biomarkers.…”

“…This hormone then stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland, triggering release of cortisol from the adrenal cortex [ 23 ]. In Cushing’s syndrome, high cortisol/ACTH ratio indicates elevated cortisol secretion from the adrenal glands; this has been proposed as a potential diagnostic biomarker for the disease [ 24 , 25 ]. Increased cortisol levels contribute to effective stress management through mobilization of glucose and tissue substrates for fuel, suppression of non-vital organ systems, and inflammation control.…”