AbstractHyponatremia is the most frequent electrolyte disorder with the syndrome of inappropriate antidiuresis (SIADH) being its predominant cause. Physiological studies in patients with SIADH are difficult to interpret due to usually several comorbidities and polymedication. Therefore, a SIADH model in healthy volunteers would be very helpful to allow insight in this complex disease and to test new therapeutic approaches. The aim of the study was to create a SIADH model with evaluation of subsequent physiological changes.The prospective interventional study on 14 healthy volunteers was carried out at the University Hospital Basel. The intervention was done by induction of hypotonic hyponatremia through hydration and administration of desmopressin. Clinical and laboratory parameters in a SIADH model were the main outcome of the measure.14 participants (64% males), BMI 23.1 kg/m2 (±2.4), aged 28.6 years (±9), completed the study. Through the intervention, serum sodium level decreased from 140 mmol/l (±1.3) to 132 mmol/l (±2.0) and serum osmolality from 286 mmol/kg (±4.7) to 267 mmol/kg (±3.5). Simultaneously urine osmolality increased to 879 mmol/kg (±97.7) and urine sodium to 213 mmol/l (±51.5) verifying the artificial SIADH model. A significant decrease of copeptin (5 pmol/l (±1.9) to 2.6 pmol/l (±0.5), p 0.002), aldosterone (314.7 pmol/l (±154.1) to 86.7 pmol/l (±23.6), p 0.019), and renin (21.2 ng/l (±26.7) to 3.6 ng/l (3.2), p 0.035) were noted, while NT-proBNP and MR-proANP significantly increased (31.7 ng/l (±18.6) to 50.5 ng/l (±33.0), p 0.001; 48.4 pmol/l (±16.8) to 56.8 pmol/l (±9.0), p 0.003).In conclusion, we were able to induce an artificial SIADH in healthy volunteers and study the changes of various hormonal biomarkers involved. This SIADH model could be helpful in evaluating diagnostic and therapeutic approaches.