Multicenter 30-year data on the 4-mg intravenous dexamethasone suppression test in the diagnosis of Cushing’s syndrome

Context The diagnosis and differential diagnosis of Cushing’s syndrome (CS) is often challenging. Objectives To evaluate the 4-mg intravenous dexamethasone suppression test (IVDST) to differentiate CS from normal subjects and subjects with Low Probability of Cushing’s (LPC), and define the cortisol responses in pituitary, adrenal, and ectopic ACTH CS. Design, Setting, Patients or Participants Data from 140 patients with surgically confirmed Cushing’s Disease (CD), five with ectopic ACTH syndrome (EAS), 26 with adrenal Cushing’s (AC), and 97 with LPC, from four tertiary hospitals between 1995-2024 were retrospectively evaluated. Thirty-two controls (normal and overweight/obese participants with or without type 2 diabetes) were previously studied. Dexamethasone was infused at 1 mg/h for 4 h. Plasma cortisol and ACTH were measured at -60 min, -5 min, +3 h, +4 h, +5 h and on Day 2 (+23 h and +23.5 h). Main Outcome Measure Sensitivity and specificity of the IVDST for the diagnosis of CS. Results Controls showed marked cortisol suppression across Days 1 and 2. In 17 of 97 patients with LPC, Day 2 cortisol overlapped with CS. Day 2 cortisol level of >130 nmol/L diagnosed CS with 97% sensitivity and 87% specificity. Conclusions The IVDST is a highly sensitive second-line diagnostic test for CS. False negative results occurred when IVDST is performed during an eucortisolemic phase of cyclic CD. The specificity of 87% emphasizes the importance of long-term follow-up of LPC. The small number of EAS cases is a major limitation in the use of IVDST to differentiate ACTH-dependent CS.