Does hypercalcaemia or calcium antagonism affect human melatonin secretion or renal excretion?

Abstract

Patients with primary hyperparathyroidism have higher serum melatonin concentrations during active disease than after surgical cure. Whether this is caused by hypercalcaemia per se, increased parathyroid hormone secretion or other mechanisms is unknown. We decided to elucidate whether exogenous hypercalcaemia influences melatonin secretion. For this purpose, eight healthy volunteers were infused with calcium and saline on separate days and in random order (experiment A). Hypercalcaemia inhibited nocturnal melatonin secretion by 20% but left urinary melatonin excretion unaffected. If exogenous hypercalcaemia inhibits melatonin secretion, it is reasonable to assume that calcium channel blockers such as verapamil might have the opposite effect. This was investigated in experiment B, in which eight healthy subjects were treated on separate occasions with oral verapamil and placebo. Verapamil did not affect nocturnal melatonin secretion but increased melatonin excretion by 145%. As 6-sulphatoxy-melatonin is the main melatonin metabolite excreted by the kidneys, it was considered important to find out whether verapamil would also influence the excretion of 6-sulphatoxy-melatonin. This was investigated in experiment C, in which eight healthy volunteers were treated, on separate occasions, with oral verapamil and placebo. In this experiment also, verapamil increased urinary melatonin excretion significantly (by 67%), but left excretion of 6-sulphatoxy-melatonin unaffected. These findings imply that verapamil influences the renal and/or hepatic handling of melatonin.

Fibromyalgia — a syndrome associated with decreased nocturnal melatonin secretion

“…In a previous study we showed that exogenous hypercalcemia causes impaired MT secretion (Wikner et al, 1997), whereas other researchers have reported that endogenous hypercalcemia might have opposite effect (Brismar et al, 1987). The s-ionized calcium level was normal in the group of patients investigated in this study.…”

Hyperparathyroidism in Hemodialyzed Patients – Relation to Melatonin and Reproductive Hormones Before and After Parathyroidectomy

“…It was suggested that hypercalcemia itself provokes the increase of melatonin. In volunteers Wikner et al (1997) proved that indeed exogenous hypercalcaemia influenced melatonin, increased its secretion and serum level by 20% but left urinary melatonin excretion unaffected.…”

Oxidative Stress in Relation to Surgery: Is There a Role for the Antioxidant Melatonin?

“…The pathophysiological mechanism behind a disturbed circadian rhythm of melatonin secretion is not known. Factors such as magnitude of surgery [12,48], anesthesia [64], perioperative administration of certain drugs (benzodiazepines [65], ␤-blockers [66], calcium channel blockers [67], nonsteroidal anti-inflammatory drugs [68], and dexamethasone), nocturnal light [69 -71], hepatic metabolism, activation of the hypothalamo-pituitary-adrenal axis [72,73], and use of opioid analgesics [74] may all affect postoperative melatonin secretion. Whether reduced endogenous secretion of melatonin after surgery has a negative effect on the oxidative status and results in increased morbidity remains to be investigated.…”