Determinants of altered sleep-wake rhythmicity in patients treated for nonfunctioning pituitary macroadenomas

In a cohort of 17 patients treated for nonfunctioning pituitary macroadenoma (NFMA), we observed alterations in polysomnographic sleep characteristics and actigraphic sleep-wake rhythmicity, and subjective fatigue, daytime somnolence, and low sleep quality. We aimed to confirm the actigraphic data in a larger scale cohort of NFMA patients, powered to address risk factors for altered rhythmicity, including the effects of hydrocortisone replacement.

Sleep-wake rhythmicity in treated NFMA patients was measured using actigraphy for 7 days, and subjective sleep quality and quality of life (QoL) with validated questionnaires. To assess the influence of hydrocortisone dependency, we additionally studied patients with Addison's disease (AD). The results were compared with matched healthy controls.

We included 69 NFMA patients in long-term remission after trans-sphenoidal surgery on stable replacement therapy for hypopituitarism, 21 AD patients, and 58 controls. NFMA patients reported severely impaired QoL, sleep quality, and increased daytime sleepiness. The day-night dichotomy of activity was fragmented, with decreased daytime activity and a tendency for increased nighttime activity. Preoperative visual field defects (VFD) were associated with this fragmentation, and vasopressin deficiency with decreased sleep efficiency, independent of age, hypopituitarism, or radiotherapy. AD patients showed similar decreases in daytime functioning, but normal subjective and objective sleep, and no daytime sleepiness.

NFMA patients suffer from altered sleep-wake rhythmicity. Hydrocortisone dependency may explain part of the decreased daytime functioning, but the independent influence of VFD and differences between AD and NFMA patients point towards a role for dysfunction of the adjacent suprachiasmatic nucleus (SCN).