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.In particular, because thePRL response to d-fenfluramine correlates with the frequency of binge/vomit episodes, it is speculated that the blunted PRL response toserotonergic stimulation represents a specific neuroendocrine correlate ofbingeing behaviour [212,252].However, in patients with binge eating 162 ___________________________________________________________________________ EATING DISORDERSdisorder, who binge without vomiting or purging and do not incurmalnutrition, the PRL response to d-fenfluramine is normal, suggesting thatthe impaired serotonergic modulation of PRL secretion in severely illbulimic patients is related to nutritional factors and not to the bingeingbehaviour [212,252].MelatoninMelatonin is the main secretory product of the pineal gland.In humans, aswell as in other species, melatonin shows a characteristic circadian rhythmwith low plasma concentrations during the day and high plasma levels atnight [321].This secretion pattern is driven by the light/dark cycle.However, other factors such as stress, nutritional patterns and body weightchanges have a role in the modulation of the melatonin circadian rhythm.Ithas been shown in animals that food deprivation increases the nocturnalsecretion of the pineal hormone [322], whereas in humans a positivecorrelation between body weight and nocturnal melatonin is reported [323].Furthermore, in obese subjects, body weight reduction profoundly affectsthe circadian profile of the hormone, with a flattening of its nocturnalsecretion and the occurrence of diurnal secretory peaks [324].Given this background and the well-known role of melatonin in theregulation of reproductive activity [321], studies have been performed toassess melatonin secretion in eating disorders.Initial works showed either areduction or no change in the 24-h melatonin secretion in severely under-weight anorexics [325,326], with the decreased nocturnal production of thehormone significantly related to concomitant depression [327].Subsequentstudies, instead, reported a profound derangement of the melatonin circadianrhythm in severely undernourished anorexics, with higher than normalplasma hormone levels throughout the 24-h cycle, secretory peaks during theday and phase changes in the nocturnal peak [215,328,329].Kennedy et al.[330,331] did not confirm a derangement of circadian rhythm of melatonin ineither emaciated or weight-restored anorexics, but reported an increaseddiurnal urinary excretion of 6-sulphatoxymelatonin (the main metabolite ofthe pineal hormone) in emaciated patients who binge and purge.Thus, itseems that in anorexia nervosa the circadian melatonin secretion is disruptedbecause of an enhanced diurnal production of the hormone, and thisalteration is more evident in anorexic patients with binge/purge behaviour.The increased diurnal secretion of melatonin could be involved in thepathophysiology of amenorrhoea, because of the inhibitory role of the pinealhormone on reproductive activity.No changes in the melatonin circadian rhythm occur in bulimia nervosa[332,333]. PHYSICAL COMPLICATIONS AND ABERRATIONS: A REVIEW ___________________ 163Central and Peripheral Appetite-regulating PeptidesA large number of central and peripheral peptides are known to beinvolved in the regulation of eating behaviour and body weight.In recentyears, several studies have investigated the possible role of these substancesin the pathophysiology of eating disorders.Interest has focused especiallyon neuropeptide Y (NPY), opioid peptides, galanin, cholecystokinin andleptin.Hypothalamic NPY is among the most potent stimulators of hunger andpreferential carbohydrate intake.Underweight anorexics have significantlyelevated CSF concentrations of NPY that do not normalize after short-termweight restoration [334].In long-term weight-restored patients the CSFconcentration of NPY is found to be normal but those weight-recoveredsubjects who continue to have amenorrhoea still have significantlyelevated concentrations of NPY [334].Because NPY is involved in themodulation of the HPG axis [335], the persistent elevation of NPY in theCSF after weight gain could contribute to persistent amenorrhoea in thosepatients
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