Endocrine Abstracts

Introduction: Patients with arginine vasopressin deficiency (AVP-D), known as central diabetes insipidus (cDI), often report psychological symptoms such as heightened anxiety levels, difficulties describing emotions, and depressed mood despite adequate treatment with desmopressin. Given the anatomical proximity, disruptions of the hypothalamic-pituitary axis causing an AVP-D could also disturb the oxytocin (OXT) system. OXT regulates socio-emotional functioning, including fear reduction, attachment, emotion recognition, and empathy. Therefore, these psychological symptoms may be caused by an additional OXT deficiency. However, OXT deficiency has not been established as a pituitary entity, as no provocation test for OXT is currently available. Here, we aimed to investigate the OXT system stimulator 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy’) as a novel biochemical and psychoactive provocation test to reveal an OXT deficiency in patients with cDI.

Methods: Randomized, placebo-controlled, double-blind, cross-over study in 15 patients with cDI and 15 matched healthy controls. Participants underwent a psychological baseline evaluation, including the assessment of anxiety levels using the State-Trait Anxiety Inventory (STAI), mood using the Beck’s Depression Inventory (BDI), and alexithymia using the Toronto Alexithymia Scale (TAS). Participants were randomized to receive either a single oral dose of MDMA (100 mg) or placebo first. OXT samples were collected at 0, 90, 120, 150, 180, and 300 minutes after drug intake. Subjective effects in response to MDMA were assessed throughout the experiment. The primary outcome was the area under the plasma OXT concentration curve (AUC) after MDMA intake.

Results: Already at baseline, patients compared with healthy controls, showed significantly higher scores in anxiety (STAI: 41 points [IQR 34-48] vs. 28 points [24-31]; P=0.02), alexithymia (TAS: 47 points [38-59] vs. 30 points [29-37; P=0.04), and depression symptoms (BDI: 6 points [3-17] vs. 1 point [0-2]; P=0.04). In response to MDMA stimulation, in patients, there was only a minimal OXT change with 66 pg/ml [16-94], while in healthy controls, OXT increased by 658 pg/ml [355-914]. The AUC was 15.8 times (1485%), i.e., 85,678 pg/ml (95%-CI [-10,800 to -63,356], P<0.001), lower in patients compared with healthy controls. This lack of OXT in patients was associated with lower subjective effects such as “good drug effect,’ “feeling high,’ “satisfaction,’ “happy,’ “trust,’ “talkative,’ “openness,’ and “fear reduction’ compared with healthy controls.

Conclusion: These results lay the groundwork for OXT deficiency as a hypothalamic-pituitary entity. In patients with cDI, this lack in OXT was associated with reduced pro-social, empathic, and anxiolytic effects.