SIR–Recently, Rodrigues Masruha et al. reported two children diagnosed as having spontaneous periodic hypothermia and hyperhidrosis. They showed low levels of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels in their patients’ cerebrospinal fluid. They concluded that this is possibly a novel neurotransmitter disorder. In their clinical letter they also referred to our patient who, in 2008, was reported as having Shapiro syndrome. However, in December 2010 we republished the case with a diagnosis of hypermelatoninemia. We reported a female having spontaneous periodic hypothermia and hyperhidrosis. She had extremely high levels of melatonin in her serum and 6-hydroxymelatonin sulfate in her urine samples during her attacks. Phototherapy and then propranolol (non-selective B1 and B2 receptor blockers) completely resolved her complaints. At a later date, we also started to treat two other patients having similar symptoms with high serum melatonin levels in our clinic. Their symptoms have been resolved under the propranalol treatment during a 2-month follow-up period (unpublished data). Rodrigues Masruha et al. also reported two females with similar problems. Their HVA and 5-HIAA levels in cerebrospinal fluid were below the normal ranges. In particular, their 5-HIAA levels were seven to eight folds below the normal level. However, our patient’s subsequent 24 hour urine studies revealed 5-HIAA at 1.9mg (normal), vanillylmandelic acid at 1.2mg (normal), and HVA at 2.2mg (normal). These data are not compatible with the Rodrigues Masruha et al. findings. However, it was not possible to examine the cerebrospinal fluid 5HIAA and HVA level in our patient. 5-HIAA is a major metabolite of serotonin, and HVA is a major metabolite of dopamine. Some experimental studies reported the attenuation of 5-HIAA and dopamine level in the brain with melatonin administration. Yoshioka et al. studied the effect of melatonin administration on the release of 5-hydroxytryptamine, 5-HIAA, DOPAC (3, 4-dihydroxyphenylacetic acid), and HVA in the suprachiasmatic nuclei of rats and reported that the release of the 5-HT metabolite and 5-HIAA was significantly reduced by this treatment. In conclusion, there are many gray areas regarding the pathophysiology of spontaneous periodic hypothermia and hyperhidrosis. However, we believe hypermelatoninemia, which may be associated with an irregular control of pinealocytes by the suprachiasmatic nucleus or related pathways, is one of the markers of this disease. We suggest the examination of the serum level of melatonin in patients with complaints of spontaneous hypothermia and hyperhydrosis.