Melatonin secretion and excretion : a clinical study focusing on factors and disease states which might influence melatonin

Abstract

The overall aim of this thesis was to find out whether other factors than the the light-dark changes influence the function of the pineal gland. Since melatonin (MT) itself, or its precursor serotonin, are of importance for sleep, mood, and pain perception, disease states - or situations in which these functions are disturbed - should be of interest to investigate in this context.

Altogether 100 individuals (51 men and 49 women) participated in the study. Seventy were healthy volunteers and 30 were patients: 7 with Wernicke-Korsakoff syndrome (WKS), 9 with Obstructive Sleep Apnea Syndrome (OSAS), 8 with Fibromyalgic Syndrome (FMS), and 6 with primary Hypothyroidism. All experiments were carried out during the night (18(20)h-08h). The lights were switched off 23h- 07h. Serum MT concentrations were determined every second hour 18(20)h-08h. Urine was collected between 22h-07h for determination of urinary MT excretion.

I. Acute alcohol intoxication induced mild hypoglychernia and inhibited the nocturnal secretion of NIT by 20-33 % in healthy volunteers. The impaired NIT secretion could not have been caused by reduced glucose provision, since oral glucose supplementation during alcohol ingestion prevented the alcohol-induced hypoglychernia but still did not normalize MT secretion.

II. Also patients with WKS, caused by chronic alcohol abuse, had a markedly reduced nocturnal secretion of MT.

III. Acute exogenous hypercalcemia decreased the nocturnal MT secretion by 20 % in healthy subjects. Calcium antagonism, in the form of oral verapamil, had no significant influence on MT secretion in normal individuals. It also failed to affect urinary excretion of 6-sulphatoxy-MT, the main MT metabolite in the urine. By contrast, verapamil increased urinary excretion of unchanged MT by 67-145 %. This suggests that verapamil may alter the renal excretion of NIT and/or change the hepatic metabolism of the hormone.

IV. Patients with OSAS usually complain of sleep disturbances and/or daytime fatigue. Although MT has sleeppromoting properties it is unlikely that the problems OSAS-patients report are caused by changed MT secretion, because this study showed that neither the nocturnal MT secretion nor the urinary MT excretion were different in these patients as compared with healthy controls. It also showed that although CPAP treatment efficiently prevented the occurrence of sleep apnea, it did neither influence the nocturnal secretion, nor the urinary excretion of MT.

V. Two dominating symptoms in patients with FMS are (besides widespread muscle pain) fatigue and sleep disturbances. This investigation showed that these patients had a 31 % lower MT secretion during the dark part of the night (23-07h) than age-, BMI-, and sex-matched controls. Previous studies have shown that FMS patients have impaired tryptophan/serotonin provision, and a higher frequency of serotonin antibodies, not only when compared with healthy controls, but also when compared with patients with other rheumatic diseases. It is possible that such mechanisms contribute to the impaired MT secretion in this group of patients.

VI. Exogenous somatostatin, in the form of subcutaneous injections of octreotide, was without significant influence on nocturnal MT secretion in normal individuals, and in patients with primary Hypothyroidism. This implies that endogenous sornatostatin may not be an important regulator of MT secretion in man.