Sleep disturbance in children with growth hormone deficiency

Hayashi, Masaharu; Shimohira, Masayuki; Saisho, Sumitaka; Shimozawa, Kazuhiko; Iwakawa, Yoshihide

doi:10.1016/s0387-7604(12)80259-2

Cited by 30 publications

(18 citation statements)

References 13 publications

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“…GH is, in fact, capable of promoting REMS; increases in REMS are reported after acute administration of GH in rats (Drucker-Colin et al, 1975), cats (Stern et al, 1975), and humans (Mendelson et al, 1980), whereas immunoneutralization of GH is followed by decreases in REMS in rats (Obál et al, 1997). GH deficiency is often associated with decreases in REMS in children, but REMS might be normal in GH-deficient young adults (Orr et al, 1977;Hayashi et al, 1992). We suggest that the decreases in REMS result from the GH deficiency in the dw/dw rat, whereas the intracerebral hGH compensates for the loss of pituitary GH and maintains normal REMS in the TH-hGH transgenic mouse.…”

Section: Discussionmentioning

confidence: 79%

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

et al. 2001

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The somatotropic axis, and particularly growth hormonereleasing hormone (GHRH), is implicated in the regulation of sleep-wake activity. To evaluate sleep in chronic somatotropic deficiency, sleep-wake activity was studied in dwarf (dw/dw) rats that are known to have a defective GHRH signaling mechanism in the pituitary and in normal Lewis rats, the parental strain of the dw/dw rats. In addition, expression of GHRH receptor (GHRH-R) mRNA in the hypothalamus/preoptic region and in the pituitary was also determined by means of reverse transcription-PCR, and GHRH content of the hypothalamus was measured. Hypothalamic/preoptic and pituitary GHRH-R mRNA levels were decreased in the dw/dw rats, indicating deficits in the central GHRHergic transmission. Hypothalamic GHRH content in dw/dw rats was also less than that found in Lewis rats. The dw/dw rats had less spontaneous nonrapid eye movement sleep (NREMS) (light and dark period) and rapid eye movement sleep (REMS) (light period) than did the control Lewis rats. After 4 hr of sleep deprivation, rebound increases in NREMS and REMS were normal in the dw/dw rat. As determined by fast Fourier analysis of the electroencephalogram (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in the dw/dw rats were only one-half of the response in the Lewis rats. The results are compared with sleep findings previously obtained in GHRH-deficient transgenic mice. The alterations in NREMS are attributed to the defect in GHRH signaling, whereas the decreases in REMS might result from the growth hormone deficiency in the dw/dw rat.

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Section: Discussionmentioning

confidence: 79%

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

et al. 2001

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“…Moreover, treatment with GH resulted in decreased TST and increased general "well-being." 45 In addition, Hayashi et al 46 reported that children with GH deficiency experience sleep disturbances and speculated that nonrefreshing sleep may impinge on a favorable outcome. However, it should be mentioned that several other studies have reported contradicting results.…”

Section: Figmentioning

confidence: 99%

Severe Hypersomnolence After Pituitary/Hypothalamic Surgery in Adolescents: Clinical Characteristics and Potential Mechanisms

Snow¹,

Gozal

Malhotra

et al. 2002

Pediatrics

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ABSTRACT. Objectives. After resection of hypothalamic/pituitary tumors, children are at risk for development of hormonal deficiencies, obesity, and hypersomnolence. However, the prevalence and pathophysiology of these complications are unclear. The purpose of this study was to assess the prevalence and severity of hypersomnolence in children after resection of pituitary tumors and to study the potential factors that contribute to this sleepiness if present. We further hypothesized that decrements in orexin levels may contribute to the sleepiness.Methods. Six children who underwent hypothalamic/ pituitary surgery were identified. Five of these patients and 5 matched control subjects underwent overnight polysomnography followed by a multiple sleep latency test. Children who had a primary sleep disorder (eg, obstructive sleep apnea) underwent treatment and were restudied subsequently (n ‫؍‬ 2). Blood levels of pituitary hormones were measured. Blood and cerebrospinal fluid (CSF) were drawn from 4 patients and 3 control subjects to measure orexin levels.Results. Endocrine control was appropriate in all children. Although patients had longer sleep duration but similar sleep efficiency than control subjects, relatively severe daytime somnolence was present (mean sleep latency: 10.3 ؎ 5.3 minutes vs 26.2 ؎ 1.1 minute in control subjects). Sleepiness did not correlate with body mass index or age. Furthermore, serum and CSF orexin levels did not differ between patients and control subjects.Conclusions. Severe daytime sleepiness is frequent among children who undergo pituitary/hypothalamic surgery and does not seem to result from inappropriate cortisol or thyroxine replacement, disturbed nocturnal sleep, or low levels of orexin in the serum or CSF. We therefore speculate that other, unidentified neurohormonal mechanisms may mediate the excessive sleepiness of these patients. Pediatrics 2002;110(6). URL: http:// www.pediatrics.org/cgi/content/full/110/6/e74; sleep, excessive daytime sleepiness, adolescents, orexin (hypocretin), brain tumors, craniopharyngioma.

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“…GH replacement therapy has improved psychological capabilities in young as well as adult GH-deficient (GHD) patients (1,2). Young GHD patients suffer from sleep disturbances and are psychologically immature (3). Untreated adult GHD patients exhibit general fatigue, lack of concentration, memory disabilities, and overall, a diminished subjective well being (4)(5)(6).…”

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confidence: 99%

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Grevès

Steensland²,

Grevès³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

111

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Studies were conducted to evaluate the effects of s.c. injected recombinant human growth hormone (GH) on the expression of the gene transcript of N-methyl-D-aspartate receptor subunits type 1 (NR1), type 2A (NR2A), and type 2B (NR2B) in the male rat hippocampus. The GH-induced effects on the expression of hippocampal gene transcripts of GH receptor (GHR) and GH-binding protein were also examined. Male Sprague-Dawley rats, kept in four groups of two different ages, was treated with the hormone or saline during 10 days before decapitation and tissue dissection. Brain tissues collected were analyzed for mRNA content by using the Northern blot technique. The results indicated that in adult young rats (11 weeks of age) the hormone elicited a decrease in the mRNA expression of NR1 but an increase in that of the NR2B subunit. In elderly adult rats (57-67 weeks of age) GH induced an increase in the expression of the hippocampal message for NR1 and NR2A. Meanwhile, the hormone induced a significant up-regulation of the GHR transcript in hippocampus of adult young rats but not in elderly adult rats. It was further found that a significant positive correlation exists between the level of GHR mRNA and the expression of the NR2B subunit transcript in adult young rats. The GH-induced increase in the expression of hippocampal mRNA for the NR2B subunit is compatible with a previously observed memory promoting effect seen for the hormone, because overexpression of this N-methyl-D-aspartate receptor subunit is shown to enhance cognitive capabilities.

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Sleep disturbance in children with growth hormone deficiency

Cited by 30 publications

References 13 publications

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

Severe Hypersomnolence After Pituitary/Hypothalamic Surgery in Adolescents: Clinical Characteristics and Potential Mechanisms

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

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