Abstract
Background: Desmopressin test (DT) is useful for the diagnosis of Cushing’s disease (CD). Approximately 80% of patients with CD respond in DT; however, the clinical significance remains unclear. Objective: To clarify the clinical significance of the responsiveness to DT in CD. Patients and Methods: This is a retrospective multi-center study. Thirty-five patients with CD who underwent DT (29 women and 6 men, age 40 ± 15 years) between 2014 and 2018 in Kobe university hospital or Toranomon hospital were included. A method of single intravenous injection of desmopressin (4μg) were used as previously described (1). Patients were divided into two groups by the responsiveness to DT; DT (+), whose ACTH increased to 1.5-folds or more during the DT (n = 20) and DT (-), whose response was less than 1.5-folds (n = 14). Following clinical parameters; age, gender, serum ACTH level, cortisol level (F), F in low dose dexamethasone suppression test, F in high dose dexamethasone suppression test, 24 hour urinary free cortisol (UFC), tumor diameter, Knosp grades, and USP8 mutation were compared between DT(+) and DT(-). Results: While serum ACTH, F, UFC and tumor size did not show any differences between these two groups, the responder was more predominant in women than men (68% vs. 17%, p = 0.028). Intriguingly, the responsiveness to DT was significantly greater in USP8 mutation-positive group (n = 15) than that in wild-type group (n = 6) (median (range); 3.0 (1.0-6.7) vs. 1.3 (1.1-1.6) folds, p = 0.010). When cutoff value is defined as 1.6-folds, the responsiveness to DT predicts the presence of USP8 mutation in the sensitivity of 80% and specificity of 100%. Conclusions: The responsiveness to DT was greater in female patients with CD. DT can predict the presence of USP8 mutation in a high specificity. These results suggest that the underlying mechanisms associated with USP8 mutation may affect the expression of V1b or V2 receptor. Reference (1) Y. Sakai, et al., Endocr J 1997;44:687-695.