Compression of the optic chiasm is associated with reduced photoentrainment of the central biological clock.

Tessel M Boertien, Eus J W Van Someren, Adriaan D Coumou, Annemieke K van den Broek, Jet H Klunder, Wing-Yi Wong, Adrienne E van der Hoeven, Madeleine L Drent, Johannes A Romijn, Eric Fliers, Peter H Bisschop

Journal: European journal of endocrinology 2022;187(6):809-821

PMID: 36201161

Abstract

OBJECTIVE

Pituitary tumours that compress the optic chiasm are associated with long-term alterations in sleep-wake rhythm. This may result from damage to intrinsically photosensitive retinal ganglion cells (ipRGCs) projecting from the retina to the hypothalamic suprachiasmatic nucleus via the optic chiasm to ensure photoentrainment (i.e. synchronisation to the 24-h solar cycle through light). To test this hypothesis, we compared the post-illumination pupil response (PIPR), a direct indicator of ipRGC function, between hypopituitarism patients with and without a history of optic chiasm compression.

DESIGN

Observational study, comparing two predefined groups.

METHODS

We studied 49 patients with adequately substituted hypopituitarism: 25 patients with previous optic chiasm compression causing visual disturbances (CC+ group) and 24 patients without (CC- group). The PIPR was assessed by chromatic pupillometry and expressed as the relative change between baseline and post-blue-light stimulus pupil diameter. Objective and subjective sleep parameters were obtained using polysomnography, actigraphy, and questionnaires.

RESULTS

Post-blue-light stimulus pupillary constriction was less sustained in CC+ patients compared with CC- patients, resulting in a significantly smaller extended PIPR (mean difference: 8.1%, 95% CI: 2.2-13.9%, P = 0.008, Cohen's d = 0.78). Sleep-wake timing was consistently later in CC+ patients, without differences in sleep duration, efficiency, or other rest-activity rhythm features. Subjective sleep did not differ between groups.

CONCLUSION

Previous optic chiasm compression due to a pituitary tumour in patients with hypopituitarism is associated with an attenuated PIPR and delayed sleep timing. Together, these data suggest that ipRGC function and consequently photoentrainment of the central biological clock is impaired in patients with a history of optic chiasm compression.

Address: Amsterdam UMC location University of Amsterdam, Endocrinology and Metabolism, Amsterdam, The Netherlands.; Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Metabolism and Nutrition, Amsterdam, The Netherlands.; Netherlands Institute for Neuroscience (NIN), Sleep and Cognition, Amsterdam, The Netherlands.; Amsterdam UMC location VU University, Psychiatry, De Boelelaan 1117, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam, The Netherlands.; VU University, Centre for Neurogenomics and Cognitive Research, Integrative Neurophysiology, Amsterdam, The Netherlands.; Amsterdam UMC location University of Amsterdam, Ophthalmology, Amsterdam, The Netherlands.; Amsterdam UMC location VU University, Internal Medicine, Section of Endocrinology, Amsterdam, The Netherlands.; Amsterdam UMC location University of Amsterdam, Internal Medicine, Amsterdam, The Netherlands.
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