Characterization of Nocturnal Ultradian Rhythms of Melatonin in Children with Growth Hormone-Dependent and Independent Growth Delay1

Abstract

To assess the existence of a possible nocturnal ultradian rhythm of melatonin in children, we analyzed 28 pediatric patients (mean age, 9.08 +/- 2.2 yr) with GH-dependent and GH-independent growth delay. Plasma melatonin was measured by RIA in children sampled every 30 min between 2100-0900 h. Statistical analysis consisted of cluster analysis to examine the presence of peaks and troughs. The pattern of melatonin levels was related to the cause of growth delay, although the means of the nocturnal concentrations of melatonin were similar in all children. Interestingly, children with a GH deficit showed a nearly normal melatonin profile, whereas children with normal GH values but abnormal growth displayed atypical profiles of melatonin. The results also prove the existence of an ultradian rhythm of melatonin in most of the patients studied. The ultradian rhythm of melatonin in children was characterized by irregular interburst intervals, thus differing from the rhythm previously described in adults that had an almost constant pulse frequency. Moreover, the existence of low and high melatonin producers was revealed in the study, a feature unrelated to the cause of growth delay. The group of children with a GH deficit showed the lowest values of integrated melatonin production and of the area of peaks and troughs. These results prove that children exhibit an ultradian rhythm of melatonin like that in adults. Whereas it is not clear whether the episodic production of melatonin is required for its biological actions, the existence of irregular pulses may reflect endocrine influences at this age and/or the immaturity of the intrinsic pulse generator.

Decreased 6-Sulfatoxymelatonin Excretion in Male GH-Deficient Children and Adolescents

“…Many studies indicate a connection between pineal gland function and the GH/IGF-1 axis in mammals; however, their results are not always synonymous. Nevertheless, in humans, there is scarce, and even contradictory, information related to melatonin secretion in GH-deficient patients [7,22]. Shulman et al [23] described that there is a modest seasonal variation in height velocity of children under GH therapy that correlates with the number of daylight hours; however, melatonin was not measured in this study.…”

“…Interestingly, other authors described contradictory results in the evaluation of melatonin secretion in children; however, these studies analyze different populations (GHD vs. idiopathic short stature children) measuring plasmatic melatonin [7,22]. In our study, the total amount of urinary 6-SM excreted was evaluated in nontreated and treated GHD children and in a control group of normal height.…”