Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls

Disruption of the hypothalamic-pituitary axis due to congenital abnormalities, tumors or head trauma may cause anterior and/or posterior pituitary deficiency also known as partial or panhypopituitarism. Patients with hypopituitarism, especially those with panhypopituitarism (i.e., anterior and posterior insufficiency) often report residual symptoms and lower quality of life despite adequate substitution treatment of deficient pituitary hormones. A recent study identified a potential oxytocin deficient state in men with combined anterior and posterior deficiency. Due to the close proximity of vasopressin and oxytocin, disruption of the vasopressin system leading to diabetes insipidus could as well disturb the oxytocin system leading to low oxytocin levels. It is therefore possible that the increased psychopathology and reduced quality of life as observed in patients with central diabetes insipidus is caused by an oxytocin deficiency. Several studies documented marked acute increases in circulating oxytocin levels in response to 3,4-methylenedioxymethamphetamine (MDMA) administration as compared to placebo in healthy volunteers.

MDMA could therefore be useful as a provocation test to detect an oxytocin deficiency in patients with central diabetes insipidus. This study is to investigate if oxytocin provocation following a single dose administration of MDMA is reduced in patients with central diabetes insipidus as compared to healthy volunteers.

Inclusion criteria

diabetes insipidus:

• Confirmed diagnosis of central diabetes insipidus

Inclusion criteria

healthy volunteers:

• Matched for age, sex, BMI and estrogen replacement/menopause/hormonal contraceptives to patients with central diabetes insipidus
• No medication, except hormonal contraception-

Exclusion criteria

• Familial central diabetes insipidus
• Participation in a trial with investigational drugs within 30 days
• Illicit substance use (with the exception of cannabis) more than 10 times in lifetime or any time within the previous two months
• Consumption of alcoholic beverages >15 drinks/week
• Tobacco smoking >10 cigarettes/day
• Cardiovascular disease (coronary artery disease, heart failure, left ventricular ejection fraction ( LVEF) <40%, stroke in the last 3 months, atrial fibrillation/flatter, Wolff-Parkinson-White syndrome (WPW)-Syndrome)
• Uncontrolled arterial hypertension (>140/90 mmHg) or hypotension (syst blood pressure <85mmHg)
• Current or previous major psychiatric disorder (e.g., major depression, schizophrenia spectrum disorder)
• Psychotic disorder in first-degree relatives
• Regular intake of selective serotonin reuptake inhibitor (SSRI), monoamine oxidase (MAO)-Inhibitors
• Pregnancy and breastfeeding
• Diagnosed chronic kidney disease (CKD) > grade III (GRF < 30ml/min)
• Diagnosed liver cirrhosis or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) levels 2.5 times above the normal range