Context Increased renal sodium reabsorption contributes to hypertension in Cushing syndrome (CS). Renal sodium transporters can be analyzed noninvasively in urinary extracellular vesicles (uEVs). Objective To analyze renal sodium transporters in uEVs of patients with CS and hypertension. Design Observational study. Setting University hospital. Participants The uEVs were isolated by ultracentrifugation and analyzed by immunoblotting in 10 patients with CS and 7 age-matched healthy participants. In 7 patients with CS, uEVs were analyzed before and after treatment. Main Outcome Measure Abundance of protein in uEVs. Results The 10 patients with CS were divided in those with suppressed and nonsuppressed renin-angiotensin-aldosterone system (RAAS; n = 5 per group). Patients with CS with suppressed RAAS had similar blood pressure but significantly lower serum potassium than patients with CS with nonsuppressed RAAS. Compared with healthy participants, only patients with suppressed RAAS had higher phosphorylated Na + -K + -Cl - cotransporter type 2 (pNKCC2) and higher total and phosphorylated Na + -Cl - cotransporter (pNCC) in uEVs. Serum potassium but not urinary free cortisol correlated with pNKCC2, pNCC, and Na + -Cl - cotransporter (NCC) in uEVs. Treatment of CS reversed the increases in pNKCC2, NCC, and pNCC. Conclusions CS increases renal sodium transporter abundance in uEVs in patients with hypertension and suppressed RAAS. Potassium has recently been identified as an important driver of NCC activity, and low serum potassium may also contribute to increased renal sodium reabsorption and hypertension in CS. These results may also be relevant for hypertension induced by exogenous glucocorticoids.,
Journal of Clinical Endocrinology and Metabolism
Department of Internal Medicine

Salih, M., Bovée, D.M. (Dominique M.), van der Lubbe, N., Danser, J., Zietse, B., Feelders, R., & Hoorn, E. (2018). Increased urinary extracellular vesicle sodium transporters in cushing syndrome with hypertension. Journal of Clinical Endocrinology and Metabolism, 103(7), 2583–2591. doi:10.1210/jc.2018-00065