Prospective Study on Salivary Evening Melatonin and Sleep before and after Pinealectomy in Humans

Abstract

Melatonin is secreted systemically from the pineal gland maximally at night but is also produced locally in many tissues. Its chronobiological function is mainly exerted by pineal melatonin. It is a feedback regulator of the main circadian pacemaker in the hypothalamic suprachiasmatic nuclei and of many peripheral oscillators. Although exogenous melatonin is approved for circadian rhythm sleep disorders and old-age insomnia, research on endogenous melatonin in humans is hindered by the great interindividual variability of its amount and circadian rhythm. Single case studies on pinealectomized patients report on disrupted but also hypersomnic sleep. This is the first systematic prospective report on sleep with respect to pinealectomy due to pinealocytoma World Health Organization grade I without chemo- or radiotherapy. Before and after pinealectomy, 8 patients completed questionnaires on sleep quality and circadian rhythm (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire), 2 nights of polysomnography, salivary evening melatonin profiles, and qualitative assessment of 2 weeks of actigraphy and sleep logs. Six patients were assessed retrospectively up to 4 years after pinealectomy. Before pinealectomy, all but 1 patient showed an evening melatonin rise typical for indifferent chronotypes. After pinealectomy, evening saliva melatonin was markedly diminished, mostly below the detection limit of the assay (0.09 pg/mL). No systematic change in subjective sleep quality or standard measures of polysomnography was found. Mean pre- and postoperative sleep efficiency was 94% and 95%, and mean sleep-onset latency was 21 and 17 min, respectively. Sleep-wake rhythm during normal daily life did not change. Retrospective patients had a reduced sleep efficiency (90%) and more stage changes, although this was not significantly different from prospective patients. In conclusion, melatonin does seem to have a modulatory, not a regulatory, effect on standard measures of sleep. Study output is limited by small sample size and because only evening melatonin profiles were assessed.

Melatonin secretion following brain midline irradiation is diminished, but not correlated with subjective sleep disturbances

“…In the complex system of human sleep and the sleep‐wake cycle, disturbances are almost always multifactorial and a lack of pineal melatonin as one of many factors might not weigh in as heavily as we had expected. This finding is supported by a recent study by Slawik et al comparing objective and subjective sleep parameters before and after surgical pinealectomy. After surgery, the patients’ night‐time salivary melatonin levels were either below the detection limit or below the physiological threshold in healthy controls.…”

“…In the complex system of human sleep and the sleep-wake cycle, disturbances are almost always multifactorial and a lack of pineal melatonin as one of many factors might not weigh in as heavily as we had expected. This finding is supported by a recent study by Slawik et al 35 Cranially irradiated patients are at risk of developing secondary CNS neoplasms, especially gliomas and meningiomas. 36,37 It cannot be excluded that an additional lack of pineal melatonin with its antioxidant qualities might render CNS cells even more vulnerable towards malignancy.…”

A critical review of melatonin assays: Past and present

“…It is not clear why some researchers using contemporary commercial assays are content to report incorrectly high levels (>5 pg/mL) of melatonin during the daytime when it is widely recognised that it is not actively being produced by the pineal gland. It is unlikely to be due to nonpineal sources of melatonin production, because (a) there are many reports showing melatonin levels <<4 pg/mL during the day and (b) people who have no pineal gland and thus no physiological source of melatonin production have extremely low (<1 pg/mL) circulating levels of melatonin …”

“…It is unlikely to be due to nonpineal sources of melatonin production, because (a) there are many reports showing melatonin levels <<4 pg/mL during the day and (b) people who have no pineal gland and thus no physiological source of melatonin production have extremely low (<1 pg/ mL) circulating levels of melatonin. 45,90 In some cases, the overestimation of daytime melatonin levels may be due to inherent poor specificity of the antibody being used. For example, the IBL melatonin antibody being used in the RIA and ELISA kits is reported to have a 1.2% cross reaction with N-acetyl serotonin and 2.5% for 5-methoxy tryptamine and 0.02% for serotonin.…”

Chronobiological Aspects of Sleep Disorders in Menopausal Women: The Role of Melatonin (Literature Review)

“…Однако в литературе встречаются данные по исследованию мелатонина после пинеалэктомии у пациентов репродуктивного возраста, когда уровень гормона в вечернее время снижался, а цикл «сон -бодрствование» сохранялся [38]. В настоящее время установлено, что эпифиз не является единственным органом, способным синтезировать мелатонин.…”