ORIGINAL ARTICLE Compression of the optic chiasm is associated with permanent shorter sleep duration in patients with pituitary insufficiency Anke J. Borgers*, Nico Romeijn†, Eus van Someren†, Eric Fliers*, Anneke Alkemade* and Peter H. Bisschop* *Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, and †Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands Summary Objective Patients with pituitary insufficiency often experience some degree of impaired sleep. Sleep–wake rhythm is regulated to a large extent by the suprachiasmatic nucleus (SCN). Because the SCN is located just superior to the optic chiasm, we hypothesized that a history of compression of the optic chiasm (CC) due to a tumour with suprasellar extension is associated with altered sleep patterns in patients with pituitary insufficiency. Design Case–control study. Patients We studied 38 patients (mean age 55Æ7 ± 13Æ1 years; 71Æ1% men) with CC and 18 patients (mean age 53Æ3 ± 16Æ6 years, 38Æ9% men) without CC. Measurements Objective measures of sleep patterns were assessed by wrist actigraphy. Validated sleep questionnaires were used to evaluate subjective sleep parameters. Results Objective total sleep duration was 36 min shorter in patients with CC than in patients without CC [454 (295–553) vs 490 (432–740) min, P =0Æ034]. Moreover, patients with CC had a later habitual bedtime [23:15 (22:30–03:00) vs 22:55 (20:00–02:00) h, P = 0Æ044] and a later actigraphic sleep onset [23:57 (22:31–01:33) vs 23Æ16 (19:47–03:04) h, P =0Æ020]. Linear regression analysis con- firmed the difference in total sleep duration after adjustment for age, sex, body mass index, cranial radiotherapy and pituitary/hypotha- lamic surgery. Subjective sleep parameters were similar in both groups. Conclusions Compression of the optic chiasm due to a tumour with suprasellar extension is associated with permanent changes in total sleep duration in patients with pituitary insufficiency. (Received 10 November 2010; returned for revision 2 December 2010; finally revised 16 March 2011; accepted 17 March 2011) Introduction Patients with pituitary insufficiency often experience some degree of fatigue or disturbed sleep despite proper endocrine substitution therapy. 1–4 The origin of these complaints is largely unknown, but warrants further examination, given the strong impact that sleep– wake disturbances have on the quality of life. 5 Hormone replacement therapy probably contributes to some extent to the experienced impairment of sleep, as interrelations between sleep and various hypothalamic–pituitary axes are well documented. 6–9 Given that hormone substitution does not com- pletely mimic endogenous hormone secretion profiles, 10 these interrelations are probably disturbed in patients with pituitary insufficiency possibly contributing to impaired sleep and fati- gue. In this light, it is not surprising that a reduced quality of life remains present despite the best possible endocrine ther- apy. 11–13 In addition to imperfect hormone substitution therapy, hypo- thalamic dysfunction may be an important causative factor of sleep impairment and fatigue. The hypothalamus is anatomically and functionally closely connected to the pituitary gland and contains one of the control centres for sleep–wake regulation: the suprachiasmatic nucleus (SCN). 14,15 The SCN is located just above the optic chiasm and may be functionally impaired after surgical and/or radiotherapeutical treatment of sellar tumours. Therefore, tumours with suprasellar extension that compress the optic chiasm may induce mechanical damage to the SCN. 2,5,7 We and others previously showed that sleep–wake alterations are present in patients after cranial radiotherapy and pituitary/ hypothalamic surgery, 3,17 but to date, no data have been pub- lished on the effect of mechanical hypothalamic damage on sleep–wake alterations. We therefore conducted a cross-sectional study to investigate whether a history of optic chiasm compression (CC) due to a tumour with suprasellar extension is associated with altered sleep patterns in patients with pituitary insufficiency. To exclude a possi- ble confounding effect of hormonal deficiencies, only patients with pituitary insufficiency on hormone replacement therapy were included. Correspondence: Anke J. F. Borgers, Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Room F5-175, 1105 AZ Amsterdam, The Netherlands. Tel.: +31 20 566 67 91; Fax: +31 20 691 76 82; E-mail: a.j.f.borgers@amc.uva.nl Clinical Endocrinology (2011) 75, 347–353 doi: 10.1111/j.1365-2265.2011.04053.x Ó 2011 Blackwell Publishing Ltd 347