Hypothalamic–pituitary–adrenal axis activity in patients with primary polydipsia compared to healthy controls

Abstract

Objective: Primary polydipsia is characterized by excessive uid intake which may suppress vasopressin levels. It is speculated that suppressed vasopressin levels lead to a dysregulated hypothalamic-pituitaryadrenal (HPA) axis as vasopressin co-modulates the HPA axis. However, data is contradictory. The aim of this study was to investigate markers of the HPA axis in patients with primary polydipsia compared to healthy controls.Design: Exploratory analysis combining data from two different prospective observational studies.Method: We included 34 patients with primary polydipsia (68% females, median aged 29.5 years (IQR 26.0, 38.8)) and 20 healthy volunteers (55% females, median age 24.0 years (IQR 22.0, 27.2)). The main outcome was circadian serum and salivary cortisol, 24-hour urinary free cortisol, and cortisol levels before and after adrenocorticotropic hormone (ACTH) stimulation.Results: No difference was seen in circadian serum cortisol levels (p=0.9), urinary free cortisol levels (p=0.17), and serum cortisol in response to ACTH stimulation (p=0.77) between patients with primary polydipsia and healthy volunteers. However, circadian salivary cortisol levels were signi cantly lower in patients with primary polydipsia as compared to healthy volunteers with an estimated difference of -3.7 nmol/l (95%-CI -5.5, -1.8 nmol/l, p=<0.001). Conclusion:Our results suggest no difference in HPA axis activity between patients with primary polydipsia and healthy volunteers. The observed difference in salivary cortisol levels may be linked to a dilution effect in saliva rather than an altered stress axis considering the other ndings.Recent studies have shown an increasing number of patients with habitual polydipsia, i.e., without associated psychiatric disorder [3,12,13], mainly in health conscious individuals. Whether primary polydipsia in these patients is also linked to an altered HPA axis activity is unknown.The aim of this study was therefore to investigate the HPA axis activity, i.e., circadian serum and salivary cortisol levels, 24-hour urinary cortisol, and cortisol in response to adrenocorticotropic hormone (ACTH) stimulation, in a larger collective of patients with psychogenic and habitual primary polydipsia and to compare the results to healthy volunteers. Methods Study design and participantsThis study combined data from two prospective studies conducted at the University Hospital Basel, Switzerland. The methodology of both studies was similar with the aim to elucidate the effect of GLP-1 receptor agonists on drinking behavior in 34 patients with primary polydipsia [14] and in 20 healthy volunteers [15] in a randomized placebo-controlled crossover design. For the present exploratory analysis, only data of participants during the placebo phase were evaluated. Full details of the studies' rationale, design, and statistical analysis have been published elsewhere [14,15]. Inclusion criteria for patients with primary polydipsia were age ≥ 18 years, polyuria of > 50 ml/kg/day, and polydipsia of > 3000 ml/day. Exclusion ...