Formerly known as central diabetes insipidus, AVD is a rare neuroendocrine condition in which fluid isn’t regulated, leading to polydipsia and polyuria. The vasopressin receptor 2 agonist desmopressin treats those symptoms, but patients often also experience psychopathological problems, such as increased anxiety, depression, and emotional withdrawal.
It has been hypothesized that those symptoms are caused by a concurrent deficiency of the so-called “love hormone” oxytocin, given the anatomic proximity of vasopressin and oxytocin production in the brain.
Now, for the first time, researchers have demonstrated evidence of that phenomenon using 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”) to provoke oxytocin release. In individuals without AVD, use of MDMA resulted in large increases in plasma oxytocin concentrations, whereas there was very little response among those with AVD, suggesting that the latter patients were deficient in oxytocin.
“These findings are suggestive of a new hypothalamic–pituitary disease entity and contribute to deepening our understanding of oxytocin as a key hormone in centrally generated socioemotional effects, as reflected by reduced prosocial, empathic, and anxiolytic effects in patients with an oxytocin deficiency,” Cihan Atila, MD, of the University of Basel (Switzerland), and colleagues wrote.
“Future studies should evaluate whether oxytocin replacement therapy can alleviate residual symptoms related to oxytocin deficiency in patients with [AVD],” they added.
The findings, from a single-center study of 15 patients with AVD and 15 healthy control persons, were published online in The Lancet Diabetes and Endocrinology.
“Atila and colleagues provide compelling evidence for a clinically relevant oxytocin deficiency in this population of patients, which appears to be at least partly responsible for the associated increase in psychopathological findings,” say Mirela Diana Ilie, MD, an endocrinologist in training at the National Institute of Endocrinology, Bucharest, Romania, and Gérald Raverot, MD, professor of endocrinology at Lyon (France) University Hospital, France, in an accompanying editorial.
“From a therapeutic viewpoint, the findings ... pave the way to intervention studies assessing the effect of intranasal oxytocin in patients with [AVD] and better clinical care for these patients,” they add.
However, Dr. Ilie and Dr. Raverot urged caution for a variety of reasons, including the fact that, thus far, only one patient with arginine vasopressin deficiency has been administered oxytocin on a long-term basis. They suggested further studies to answer many pertinent questions, such as what the appropriate doses and frequency of oxytocin administration are, whether the dose should remain constant or be increased during stress or particular acute situations, whether long-term administration is suitable for all patients regardless of the extent of oxytocin deficiency, and how follow-up should be conducted.
“Answering these questions seems all the more important considering that oxytocin therapy has shown conflicting results when administered for psychiatric disorders,” said Dr. Ilie and Dr. Raverot.
In the meantime, “independent of the potential use of oxytocin, given the frequent and important psychological burden of [AVD], clinicians should screen patients for psychological comorbidities and should not hesitate to refer them to appropriate psychological and psychiatric care,” the editorialists wrote.