Deciphering the Role of Vasopressin in Primary Aldosteronism

CONTEXT: The role of vasopressin (AVP) in the pathophysiology of primary aldosteronism (PA) remains unclear. OBJECTIVES: The primary aim of this study was to investigate AVP secretion in PA by measuring the plasma concentration of copeptin (PCop), the C-terminal portion of provasopressin. The secondary aim was to assess renal sensitivity to AVP. DESIGN AND SETTING: This was a cross-sectional study in a tertiary-care hospital. PROTOCOL: We recruited 115 patients with PA, 48 patients with essential hypertension (EH), and 108 normotensive healthy subjects (HS). Blood was sampled for biochemical and hormonal evaluations in fasting condition after 1-h rest in supine position. Osmolality was determined in 24-h urine. PCop was determined by immunoassay. MAIN OUTCOME MEASURE: The main outcome measure was adjusted difference in PCop between groups. RESULTS: After adjustment for sex, body mass index, systolic blood pressure, natremia, and kalemia, PCop was significantly higher in patients with PA than in HS (geometric mean ratio, 1.61; 95% confidence interval [CI], 1.26-2.06; P < .0001) and patients with EH (1.40; 95% CI, 1.08-1.82; P = .0070) PCop was positively correlated with natremia (P = .0094). Urine osmolality was significantly lower in patients with PA than in HS (0.82; 95% CI, 0.74-0.92; P = .0002) and 24-h urinary output was significantly higher in patients with PA than in HS (1.32; 95% CI, 1.11-1.56; P = .0005). The relationship between urine osmolality and PCop was shifted downward in patients with PA but was similar in patients with EH and HS, indicating peripheral resistance to AVP. CONCLUSION: PCop increases in patients with PA in response to an increase in natremia and a renal resistance phenomenon, indicating that AVP release is chronically stimulated in PA.