Primary polydipsia in the medical and psychiatric patients

Background: Primary polydipsia is characterized by increased fluid intake and consistent excretion of profound quantities of diluted urine. It has mainly been described in psychiatric patients but with the current lifestyle-trend and believe that fluid intake is healthy, it is speculated to be increasing in the general population. One of the main and most severe complications of primary polydipsia is hyponatremia, which occurs when free water intake exceeds free water excretion. Despite the increasing prevalence, consistent clinical data on patients with primary polydipsia is lacking. Most of the existing data stems from case reports and retrospective studies within the psychiatric setting, particularly from patients with a schizophrenia spectrum disorder. Pathophysiological understanding and the risk for hyponatremia in non-psychiatric patients remains unclear. Treatment options for patients with primary polydipsia are scarce and have mainly been studied in the psychiatric setting.
Objective: This MD-PhD thesis aims at contributing to improving the pathophysiological understanding of, to characterize complications in, and to find treatment options for patients with primary polydipsia.
Methods: To reach the aspired aim, I first performed a secondary analysis of a prospective observational study to characterize patients with primary polydipsia hospitalized with profound hyponatremia. Second, I investigated the association of hyponatremia and outdoor temperature in patients with and without primary polydipsia in three distinct cohorts. Third, I was involved in a randomized, placebo-controlled cross-over trial evaluating glucagon-like peptide-1 receptor agonists, medications used to treat type 2 diabetes mellitus and obesity, as a treatment option for patients with primary polydipsia.
Results: First, primary polydipsia’s main complication, i.e. hyponatremia, also occurs in medical patients also without psychiatric comorbidities. Second, the risk of profound hyponatremia increases in all polydisic patients in the presence of contributing factors impairing the renal excretory capacity: low solute intake or increased arginine vasopressin. Primary polydipsia in association with profound hyponatremia is furthermore associated with a poor outcome, e.g. hyponatremia recurrence, rehospitalization, and death. Third, hyponatremia shows a season dependent effect with increased hyponatremia prevalence during summer months in correlation with increased outdoor temperature. Fourth, glucagon-like peptide-1 receptor agonists reduce fluid intake in patients with primary polydipsia.
Conclusion: Primary polydipsia has mainly been described in the psychiatric setting, but it seems to be also common in the general population. Special attention should be paid in patients with primary polydipsia to reduce hyponatremia inducing factors and prevent hyponatremia. Glucagon-like peptide- 1 receptor agonists are a promising new treatment option for patients with primary polydipsia.