Objective: Differentiating Cushing’s syndrome (CS) from Pseudo-Cushing’s (Low Probability of Cushing’s [LPC]) may be difficult. We evaluated the 4-mg intravenous dexamethasone suppression test (IVDST) to differentiate CS from normal subjects and LPC, and to define responses in CS of various causes.
Design: Data from 114 patients with Cushing’s Disease (CD) who underwent IVDST(s) before their first pituitary operation (CDa), 27 patients who had repeat IVDST(s) after first pituitary operation (CDb), 22 with adrenal Cushing’s (AC), four with ectopic ACTH syndrome (EAC) and 69 with LPC, from four tertiary hospitals between 1995 to 2020 were retrospectively evaluated. Thirty-two control subjects (normal and overweight/obese participants with or without type 2 diabetes) were previously studied. Dexamethasone was infused at 1 mg/h for 4h. Plasma cortisol and ACTH were measured at -60 min (baseline), -5 min, +3h, +4h, +5h and at +23h and +23.5h on Day 2.
Results: Day 2 cortisol level of >130 nmol/L (or >30% of baseline) diagnosed CS with 99% sensitivity and 91% specificity. CDa group demonstrated partial suppression of cortisol, with rebound hypercortisolism on day 2 in 88% of patients. Six patients in CDb with suspected recurrence had day 2 cortisol levels <130 nmol/L. Cortisol levels did not suppress in AC or EAS. In 9 of 69 patients with LPC, day 2 cortisol overlapped with CS. Control subjects showed marked suppression of cortisol, maintained on Day 2.
Conclusion: IVDST has high sensitivity for diagnosis of CS. False negative results may occur in patients with surgically-proven CD when IVDST is performed during mild disease, quiescent phase, early recurrence, or with low volume ACTH-secreting pituitary tumour. The specificity of 91% is lower than previously reported (96%), highlighting the importance of long-term follow-up of LPC. Because only four EAC were studied, the utility of IVDST in differential diagnosis of ACTH-dependent CS is uncertain.