The usefulness of the combined high-dose dexamethasone suppression test and desmopressin stimulation test in establishing the source of ACTH secretion in ACTH-dependent Cushing’s syndrome

• Published in: ENDOCRINE JOURNAL Vol. 68; no. 7; pp. 839 - 848
• Main Authors: Liu, Hui, Zhang, Weiwei, Jiang, Shu, Tan, Huiwen, Yu, Yerong, Chen, Yaxi, Qiao, Jingtao, Wang, Chun, Li, Jianwei, Li, Jiaqi, Cai, Bowen
• Format: Journal Article
• Language: English
• Published: Japan The Japan Endocrine Society 01.01.2021; Japan Science and Technology Agency
• Subjects: Adrenocorticotropic hormone; Adrenocorticotropic Hormone - metabolism; Adult; Bilateral inferior petrosal sinus sampling (BIPSS); Circadian Rhythm - physiology; Cortisol; Cushing Syndrome - blood; Cushing Syndrome - diagnosis; Cushing's disease; Cushing’s disease (CD); Deamino Arginine Vasopressin; Desmopressin; Desmopressin stimulation test (DDAVP test); Dexamethasone; Diagnosis, Differential; Diagnostic Tests, Routine; Differential diagnosis; Ectopic ACTH syndrome (EAS); Female; High-dose dexamethasone suppression test (HDDST); Hormones; Humans; Hydrocortisone - metabolism; Male; Middle Aged; Nervous system diseases; Pituitary; Retrospective Studies; Sensitivity and Specificity; Young Adult; Cushing’s disease (CD); Ectopic ACTH syndrome (EAS); Desmopressin stimulation test (DDAVP test); High-dose dexamethasone suppression test (HDDST); Bilateral inferior petrosal sinus sampling (BIPSS)
• ISSN: 0918-8959; 1348-4540; 1348-4540
• DOI: 10.1507/endocrj.EJ20-0837

Bilateral inferior petrosal sinus sampling (BIPSS) is the current gold standard test for differentially diagnosing ACTH-dependent Cushing’s syndrome (CS). However, BIPSS is an invasive procedure, and its availability is limited. We retrospectively analysed the 24-hour urinary free cortisol (UFC) level during the high-dose dexamethasone suppression test (HDDST) and plasma ACTH/cortisol levels after the desmopressin stimulation test (DDAVP test) in subjects with confirmed Cushing’s disease (CD) (n = 92) and ectopic ACTH-dependent CS (EAS) (n = 16), and evaluated the positive predictive value (PPV) of the two combined-tests in the aetiological diagnosis of ACTH-dependent CS. The percent changes in UFC levels after the HDDST and in ACTH/cortisol levels after DDAVP administration relative to the corresponding basal levels and the area under the receiver operating characteristic (ROC) curve (AUC) were analysed. UFC suppression below 62.7% suggested a pituitary origin with a sensitivity (SE) of 80% (95% CI: 70–88) and a specificity (SP) of 80% (95% CI: 52–96). A threshold increase in the ACTH level after DDAVP stimulation of 44.6% identified CD with an SE of 91% (95% CI: 83–97) and an SP of 75% (95% CI: 48–93). The combination of both tests yielded an SE of 95.5% and PPV of 98.4% for CD, and significantly improved the efficiency of the differential diagnosis between CD and EAS. These dual non-invasive endocrine tests may substantially reduce the need for BIPSS in the etiological investigation of ACTH-dependent CS.