Overview

Hypothalamus has a key role in multiple vital functions, including regulation of sleep-wake cycles. Oxytocin (OT), a neurohormone synthetized in the hypothalamus, has a wide range of physiological functions, including a putative role in improving sleep quality. Hypothalamic and pituitary damage (HPD) is associated with a clinically relevant OT deficient state and multiple and severe comorbidities including poor sleep quality, that have a well-known negative impact on general health and quality of life (QoL). Several factors may coexist in the pathophysiology of sleep disorders (SD) in HPD and SD might be a keystone in the persistence of some of the comorbidities observed in HPD. Therefore, appropriate identification and understanding of the mechanisms contributing to SD in HPD is mandatory to choose adequate preventive strategies and treatment. This project is aimed to (1) identify the prevalence of SD in HPD, (2) to determine OT role in sleep quality and (3) to identify potential mechanisms and mediators of sleep quality and their associations with clinical outcomes in patients with HPD with the ultimate goal of identifying preventive and therapeutic targets. We will use a controlled cross-sectional design of patients with HPD and sex-, BMI-, age- matched controls and an innovative cross-disciplinary approach bridging neuroendocrinology, psychology, neurophysiology, neuroimaging, nuclear medicine and neuroophthalmology disciplines to learn about the prevalence of SD in HPD and to disentangle the underpinning mechanisms behind SDs in HPD. The results of this project will be an extremely important step towards optimizing therapy for patients with HPD who have higher mortality and poor QoL despite appropriate hormone replacement therapy.

Eligibility

Inclusion Criteria:

• Patients with hypothalamic-pituitary dysfunction (HPD) with at least one pituitary hormone deficiency and at least one clinical sign of hypothalamic damage (e.g., arginine-vasopressin deficiency (AVP-D) and/or severe obesity and/or hyperphagia; MRI suggestive of hypothalamic damage; traumatic brain injury; radiotherapy in the sellar region and/or brain tumors affecting the hypothalamus).
• Healthy controls matched for BMI, age, and sex.

Exclusion Criteria:

• Poor control of hormonal deficiencies in the previous 6 months.
• Use of new psychoactive drugs in the last 3 months or occasional use.
• Clinically significant liver, lung, kidney, and cardiovascular disease.
• Any neurological condition affecting brain function (stroke, dementia, uncontrolled epilepsy with recent seizures).
• Uncontrolled diabetes mellitus.
• Active psychosis.
• Ophthalmology: total blindness, Glaucoma, uveitis, visual acuity \<0.6, or eye surgery in the previous 6 months.
• Any acute illness that the investigator determines may interfere with study participation or safety.
• Pregnancy or breastfeeding.
• Patients who refuse or are unable to provide written informed consent.
• In controls: presence of brain or pituitary tumor, radiation involving the hypothalamus or pituitary, and history of hypopituitarism.