The Pinealoprive Syndrome: Myth or Reality?

Although the role of melatonin in many biological functions, foremost among them the regulation of circadian rhythms and sleep, has been widely demonstrated, the definition of a specific disorder linked to melatonin deficiency remains debated. As the main function of the pineal gland is to secrete melatonin, pineal lesions and pinealectomy provide insightful models for understanding the effect of acute and chronic suppression of melatonin secretion ("pinealoprive syndrome"). In pineal parenchymal cell tumor, melatonin levels are usually normal/high, whereas impaired secretion is thought to reflect parenchymal destruction and thus tumors with malignant profiles. Following pinealectomy, low or undetectable levels of melatonin are observed, suggesting that melatonin assay may be used to monitor complete tumoral and pineal gland resection. However, the link between melatonin depletion in this context and the objective/subjective quality of sleep remains unclear. Likewise, while melatonin is involved in a large number of physiological functions, damage to the pineal gland does not appear to have any clear extra-neurological effects. This paradox might be explained by the presence of extra-pineal melatonin secretion sites. In addition, it is possible that the effects of melatonin depletion are long term, in real-life situations, and fluctuate according to the season. Importantly, most evidence relies on very small samples due to the rarity of pineal gland lesions. Further prospective longitudinal studies on wider cohorts are needed, to definitively conclude on the impact of pineal gland-related melatonin on health in general and sleep in particular. There is therefore no recommendation for melatonin supplementation after pinealectomy. Pragmatically, in the presence of melatonin deficiency and sleep disorders in the context of pineal gland tumor/pinealectomy, and given the safety of melatonin as a medication, it seems reasonable to propose exogenous melatonin, with a chronobiotic or sedative purpose depending on the type of disorder.