No abstract

Objective: The prognostic/diagnostic biomarker copeptin, an arginine vasopressin surrogate, reflects physical stress. Whether copeptin concentration increases upon psychological stress is unknown. We investigated psychological stress effects on copeptin secretion in healthy volunteers and patients with central diabetes insipidus (DI). Design: A prospective observational study was conducted to study the relation between copeptin concentration and psychological stress. Methods: A total of 20 healthy adults (ten female) and eight patients with central DI (four female) underwent the Trier Social Stress Test including, in order, 30-min waiting period, 10-min anticipation period, 10-min test period and 40-min recovery. Serum copeptin and cortisol concentrations and self-rated stress component feelings were determined in the pre-/postanticipation period, post-test period and twice post-recovery. Results: In healthy volunteers, the median (25th-75th percentile) copeptin concentration peaked immediately during the post-test period at 5.1 (3.2-7.0) pmol/l, vs 3.7 (2.6-5.4) pmol/l at baseline. Over the measurement course, copeptin concentration significantly elevated (coefficient; 95% CI) (0.14; 0.06-0.23, PZ0.002). The important predictors of increase in copeptin concentration were feelings of tension (0.06; 0.04-0.08, P!0.001) and avoidance (0.07; 0.04-0.10; P!0.001). Copeptin and cortisol levels were associated (0.43; 0.13-0.72, P!0.005). Patients with DI had lower baseline concentrations (1.55 (1.2-3.1) pmol/l) when compared with healthy volunteers, PZ0.006. Patients with DI showed no increase upon psychological stress (peak 2.15 pmol/l (1.5-2.28), PZ0.79). By contrast, cortisol values were similar in patients and volunteers. Conclusions: In healthy volunteers, copeptin levels significantly increased after psychological stress testing; this response was blunted in patients with DI.

BackgroundTreatment options to address the hyponatremia induced by the syndrome of inappropriate antidiuresis (SIAD) are inadequate. The sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresis via urinary glucose excretion and therefore, might offer a novel treatment option for SIAD.MethodsIn this double-blind, randomized trial, we recruited 88 hospitalized patients with SIAD-induced hyponatremia <130 mmol/L at the University Hospital Basel from September 2016 until January 2019 and assigned patients to receive, in addition to standard fluid restriction of <1000 ml/24 h, a once-daily dose of oral empagliflozin or placebo for 4 days. The primary end point was the absolute change in plasma sodium concentration after 4 days of treatment. Secondary end points included predisposing factors for treatment response and safety of the intervention.ResultsOf the 87 patients who completed the trial, 43 (49%) received treatment with empagliflozin, and 44 (51%) received placebo. Baseline plasma sodium concentrations were similar for the two groups (median 125.5 mmol/L for the empaflozin group and median 126 mmol/L for the placebo group). Patients treated with empagliflozin had a significantly higher increase of median plasma sodium concentration compared with those receiving placebo (10 versus 7 mmol/L, respectively; P=0.04). Profound hyponatremia (<125 mmol/L) and lower baseline osmolality levels increased the likelihood of response to treatment with empagliflozin. Treatment was well tolerated, and no events of hypoglycemia or hypotension occurred among those receiving empagliflozin.ConclusionsAmong hospitalized patients with SIAD treated with fluid restriction, those who received empagliflozin had a larger increase in plasma sodium levels compared with those who received placebo. This finding indicates that empagliflozin warrants further study as a treatment for the disorder.

The stress hormone copeptin, which is co-secreted with arginine vasopressin, increases in seriously ill patients and can predict outcome in several organic diseases. Information about the influence of psychological stress on copeptin levels is lacking, but is important for interpretation of copeptin levels in the clinical setting. The aim of this study was to evaluate the influence of psychological stress on copeptin levels. We measured copeptin levels in 25 healthy medical students before and after a written examination. The primary endpoint was change in copeptin levels from immediately prior to examination compared with after the examination. Median copeptin levels prior to the examination were significantly higher than those after its conclusion. Similar results were found for serum cortisol and salivary cortisol. Serum cortisol prior to examination was significantly higher in students with a superior examination result, compared to those with a lower score. In conclusion, psychological stress leads to a subtle increase in copeptin level and might therefore be taken into account as a confounding factor in disorders with small diagnostic copeptin range. Higher cortisol levels, but not copeptin, correlated with a better academic performance in this cohort of students.