Six hundred thirty adults without known Cushing syndrome, cardiovascular or renal disease completed a restricted dietary sodium diet (10 mmol/d, 230 mg/d) followed by cross-over to a liberalized dietary sodium diet (200 mmol/d, 4600 mg/d). Twenty-four-hour urine collection and biochemical investigations were performed at the end of each dietary intervention. Mean 24-hour urinary free cortisol increased with liberalized sodium intake when compared with restricted sodium intake (178.0 ± 89.7 vs 121.3 ± 65.6 nmol/d, P < .001). Nearly all participants (84%) had an increase in the urinary free cortisol following liberalized sodium intake. This translated to a substantial difference in the proportion of participants exceeding categorical thresholds of urinary cortisol on liberalized vs restricted sodium intake: 62% vs 27% for 138 nmol/d (50 mcg/d), 46% vs 17% for 166 nmol/d (60 mcg/d), 32% vs 10% for 193 nmol/d (70 mcg/d), 23% vs 6% for 221 nmol/d (80 mcg/d), 17% vs 4% for 248 nmol/d (90 mcg/d). In parallel, there was a small decrease in morning total serum cortisol with liberalized sodium intake (303.0 ± 117.3 vs 326.4 ± 162.5 nmol/L, P < .001). Increased dietary sodium intake increases urinary free cortisol excretion and may increase the risk for false-positive results. Variations in dietary sodium intake may influence the interpretations of cortisol measurements performed to evaluate for hypercortisolism.
