Insomnia Abstracts 8




Risk of Autoimmune Disease in Adults with Chronic Insomnia Requiring Sleep-Inducing Pills: A Population-Based Longitudinal Study.
            (Kok et al., 2016) Download
BACKGROUND:  Recent studies indicate that chronic insomnia is associated with the development of certain somatic diseases. Whether it would be associated with the development of an autoimmune disease (AID) was unknown. OBJECTIVE:  We aimed to examine the association and quantify the magnitude of risk for AID in individuals suffering from chronic insomnia requiring sleep-inducing pills. DESIGN:  This was a population-based, nationwide longitudinal study. PARTICIPANTS:  Using a claims data set containing 1 million randomly sampled, insured subjects derived from the National Health Insurance Research Database, we assembled a chronic insomnia group and a 1:3 propensity score-matched comparison group (CP), which were balanced in terms of sex, age, insurance premium, urbanization, alcohol use disorder, smoking-related diagnoses, and morbid obesity. MAIN MEASURES:  Person-time data with incidence rate, adjusted hazard ratios (aHR) by the Cox model, AID-free survival functions compared with the log-rank test, and a sensitivity analysis on the time lag effect were presented. Incident AID within the first year of follow-up were excluded. The error rate was controlled using the Benjamini-Hochberg procedure. KEY RESULTS:  With 39,550 and 129,914 person-years' follow-up for the chronic insomnia and CP groups (n = 5,736 and 17,208), respectively, we found an increased risk for subsequent AID, representing a 70 % increase in the aHR (1.7; 95 % confidence interval [CI], 1.5-1.9, p < 0.0001). A positive association between chronic insomnia and primary Sjögren's syndrome (pSS) was observed (aHR, 1.3; 95 % CI, 1.1-1.6). Sensitivity analysis disclosed that AID risk was even stronger after 5 years of follow-up (aHR, 2.0; 95 % CI, 1.7-2.4). CONCLUSION:  Chronic insomnia requiring sleep-inducing pills may be associated with a 70 % increased risk for future AID, particularly pSS.


Capsule Commentary on Kok et al., Risk of Autoimmune Disease in Adults with Chronic Insomnia Requiring Sleep-Inducing Pills: A Population-Based Longitudinal Study.
(Qato, 2016) Download
In this study, chronic insomnia was associated with an adjusted hazard ratio of 1.7 (95 % confidence interval, 1.5– 1.9) for subsequent autoimmune disease development. The authors conclude that there is a 70 % increased risk of future autoimmune disorder in enrollees with chronic insomnia and speculate that the causal link is the impact of chronic insomnia on neuroimmunological functioning. This conclusion should be tempered by the fact that insomnia is often underdiagnosed and undertreated,4 resulting in potential misclassification of the exposure and thus misestimation of the hazard ratio.
Perhaps more importantly, in order to appreciate the mag- nitude of the difference in risk, hazard ratios should be interpreted in the context of time.5 The authors did not provide information on the median time to disease devel- opment to enable readers to compare time to diagnosis between the groups. While this information may not change the direction of the findings, it will impact the interpretation and the urgency with which the study results are communicated to concerned patients most at risk for developing autoimmune disorders. Despite these limita- tions, this work reaffirms the critical need for providers to focus attention on sleep disturbance as a potential predictor of disease.

Autoimmune sleep disorders.
            (Silber, 2016) Download
A number of autoantibodies, some paraneoplastic, are associated with sleep disorders. Morvan syndrome and limbic encephalitis, associated with voltage-gated potassium channel-complex antibodies, principally against CASPR2 and LGI1, can result in profound insomnia and rapid eye movement sleep behavior disorder (RBD). Patients with aquaporin-4 antibodies and neuromyelitis optica may develop narcolepsy in association with other evidence of hypothalamic dysfunction, sometimes as the initial presentation. Central sleep apnea and central neurogenic hypoventilation are found in patients with anti-N-methyl-d-aspartate receptor antibody encephalitis, and obstructive sleep apnea, stridor, and hypoventilation are prominent features of a novel tauopathy associated with IgLON5 antibodies. In addition, paraneoplastic diseases may involve the hypothalamus and cause sleep disorders, particularly narcolepsy and RBD in those with Ma1 and Ma2 antibodies. Patients with antineuronal nuclear autoantibodies type 2 may develop stridor. Several lines of evidence suggest that narcolepsy is an autoimmune disorder. There is a strong relationship with the human leukocyte antigen (HLA) DQB1*06:02 haplotype and polymorphisms in the T-cell receptor alpha locus and purinergic receptor P2Y11 genes. Patients with recent-onset narcolepsy may have high titers of antistreptococcal or other antibodies, although none has yet been shown to be disease-specific but, supporting an immune basis, recent evidence indicates that narcolepsy in children can be precipitated by one type of vaccination against the 2009-2010 H1N1 influenza pandemic.



How (and why) the immune system makes us sleep.
            (Imeri and Opp, 2009) Download
Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value.

Experimental immunomodulation, sleep, and sleepiness in humans.
            (Pollmächer et al., 2000) Download
Infection, inflammation, and autoimmune processes are accompanied by serious disturbances of well-being, psychosocial functioning, cognitive performance, and behavior. Here we review those studies that have investigated the effects of experimental immunomodulation on sleep and sleepiness in humans. In most of these studies bacterial endotoxin was injected intravenously to model numerous aspects of infection including the release of inflammatory cytokines. These studies show that human sleep-wake behavior is very sensitive to host defense activation. Small amounts of endotoxin, which affect neither body temperature nor neuroendocrine systems but slightly stimulate the secretion of inflammatory cytokines, promote non-rapid-eye-movement sleep amount and intensity. Febrile host responses, in contrast, go along with prominent sleep disturbances. According to present knowledge tumor necrosis factor-alpha (TNF-alpha) is most probably a key mediator of these effects, although it is likely that disturbed sleep during febrile host responses involves endocrine systems as well. There is preliminary evidence from human studies suggesting that inflammatory cytokines such as TNF-alpha not only mediate altered sleep-wake behavior during infections, but in addition are involved in physiological sleep regulation and in hypnotic effects of established sedating drugs.

Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime.
            (Vgontzas et al., 2002) Download
Chronic insomnia, by far the most commonly encountered sleep disorder in medical practice, is characterized by difficulty falling or staying asleep at night and increased fatigue during the day. Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are fatigue-inducing cytokines, and the daytime secretion of IL-6 is negatively influenced by the quantity and quality of the previous night's sleep. We hypothesize that the poor quality of insomniacs' sleep is associated with a hypersecretion of these 2 cytokines during the daytime, which, in turn, correlates with the fatigue experienced by these patients. Eleven young insomniacs (6 men and 5 women) and 11 (8 men and 3 women) age- and body mass index (BMI)-matched healthy controls participated in the study. Subjects were recorded in the sleep laboratory for 4 consecutive nights and serial 24-hour plasma measures of IL-6 and TNF were obtained during the 4th day. Insomniacs compared to controls slept poorly (sleep latency and wake were increased, whereas percentage sleep time was decreased during baseline nights, all P <.05). The mean 24-hour IL-6 and TNF secretions were not different between insomniacs and controls. However, the difference in the change (increase) of IL-6 plasma levels from midafternoon (2 PM) to evening (9 PM) between insomniacs and controls was significant (P <.01). Furthermore, cosinor analysis showed a significant shift of the major peak of IL-6 secretion from nighttime (4 AM) to evening (7 PM) in insomniacs compared to controls (P <.05). Also, while TNF secretion in controls showed a distinct circadian rhythm with a peak close and prior to the offset of sleep (P <.05), such a rhythm was not present in insomniacs. Finally, daytime secretion of TNF in insomniacs was characterized by a regular rhythm of 4 hours (P <.05); such a distinct periodicity was not present in controls. We conclude that chronic insomnia is associated with a shift of IL-6 and TNF secretion from nighttime to daytime, which may explain the daytime fatigue and performance decrements associated with this disorder. The daytime shift of IL-6 and TNF secretion, combined with a 24-hour hypersecretion of cortisol, an arousal hormone, may explain the insomniacs' daytime fatigue and difficulty falling asleep.



Association Between Thyroid Function and Objective and Subjective Sleep Quality in Older Men: The Osteoporotic Fractures in Men (MrOS) Study.
            (Akatsu et al., 2014) Download
OBJECTIVE:  To determine the association between thyroid hormone levels and sleep quality in community-dwelling men. METHODS:  Among 5,994 men aged ≥65 years in the Osteoporotic Fractures in Men (MrOS) study, 682 had baseline thyroid function data, normal free thyroxine (FT4) (0.70 ≤ FT4 ≤ 1.85 ng/dL), actigraphy measurements, and were not using thyroid-related medications. Three categories of thyroid function were defined: subclinical hyperthyroid (thyroid-stimulating hormone [TSH] <0.55 mIU/L), euthyroid (TSH, 0.55 to 4.78 mIU/L), and subclinical hypothyroid (TSH >4.78 mIU/L). Objective (total hours of nighttime sleep [TST], sleep efficiency [SE], wake after sleep onset [WASO], sleep latency [SL], number of long wake episodes [LWEP]) and subjective (TST, Pittsburgh Sleep Quality Index score, Epworth Sleepiness Scale score) sleep quality parameters were measured. The association between TSH and sleep quality was examined using linear regression (continuous sleep outcomes) and log-binomial regression (categorical sleep outcomes). RESULTS:  Among the 682 men examined, 15 had subclinical hyperthyroidism and 38 had subclinical hypothyroidism. There was no difference in sleep quality between subclinical hypothyroid and euthyroid men. Compared to euthyroid men, subclinical hyperthyroid men had lower mean actigraphy TST (adjusted mean difference [95% confidence interval (CI)], -27.4 [-63.7 to 8.9] minutes), lower mean SE (-4.5% [-10.3% to 1.3%]), and higher mean WASO (13.5 [-8.0 to 35.0] minutes]), whereas 41% had increased risk of actigraphy-measured TST <6 hours (relative risk [RR], 1.41; 95% CI, 0.83 to 2.39), and 83% had increased risk of SL ≥60 minutes (RR, 1.83; 95% CI, 0.65 to 5.14) (all P>.05). CONCLUSION:  Neither subclinical hypothyroidism nor hyperthyroidism is significantly associated with decreased sleep quality.

Total sleep deprivation and the thyroid axis: effects of sleep and waking activity.
            (Gary et al., 1996) Download
BACKGROUND:  Circadian and sleep components modulate anterior pituitary release of thyrotropin (TSH), the chemical substance regulating the thyroid hormones, thyroxine (T4), and triiodothyronine (T3). The present study examined TSH, T4, and T3 concentrations across the wake-sleep boundary time (2300-0130 hours) before, during, and after a 64-h sleep deprivation paradigm. Additionally, adrenocorticotropic hormone (ACTH) and cortisol were measured as an index of hypothalamic-pituitary-adrenal axis activation. Activity levels and ratings of effort required to perform cognitive tasks were also incorporated to evaluate physical and cognitive load, respectively, across the study period. Assessing the combined effects of activity and sleep deprivation on thyroid hormone economy is relevant to the relationship of high physical and/or cognitive performance demands during sleep deprivation inherent in extended military operations and space exploration. METHODS:  There were 12 healthy subjects who were monitored during a 2-d baseline period, 3 d of total sleep deprivation, and 2 nights of recovery sleep. Serum samples were collected at 2300 hours and 0130 hours across the entire study period, and measured for TSH, T4, T3, and glucocorticoids. RESULTS:  Change scores evaluated at the wake-sleep boundary time demonstrated significant inhibitory effects of sleep on thyroid hormone measures. As expected, sleep deprivation was associated with elevated TSH. However, sleep deprivation also significantly increased circulating levels of T3 at 2300 hours and T4 concentration change scores (2300-0130 hours). Glucocorticoid levels did not track thyroid hormone changes. Physical activity remained constant while subjective ratings of effort to perform cognitive tasks increased significantly during sleep deprivation. CONCLUSION:  Compared to sleep deprivation studies under constant conditions reporting no change in peripheral T4 and T3 levels, the present study suggests activity level, including cognitive effort to perform, during total sleep deprivation may produce substantive changes in the thyroid axis.

Changes in serum TSH and free T4 during human sleep restriction.
            (Kessler et al., 2010) Download
STUDY OBJECTIVES:  To examine whether recurrent sleep restriction is accompanied by changes in measures of thyroid function. DESIGN:  Two-period crossover intervention study. SETTING:  University clinical research center and sleep laboratory. PARTICIPANTS:  11 healthy volunteers (5F/6M) with a mean (+/- SD) age of 39 +/- 5 y and BMI 26.5 +/- 1.5 kg/m2. INTERVENTION:  Randomized exposure to 14 days of sedentary living with ad libitum food intake and 5.5- vs. 8.5-h overnight sleep opportunity. MEASUREMENTS AND RESULTS:  Serum thyroid-stimulating hormone (TSH) and free thyroxine (T4) were measured at the end of each intervention. Partial sleep restriction was accompanied by a modest but statistically significant reduction in TSH and free T4, seen mainly in the female participants of the study. CONCLUSIONS:  Compared to the well-known rise in TSH and thyroid hormone concentrations during acute sleep loss, tests obtained after 14 days of partial sleep restriction did not show a similar activation of the human thyroid axis.

Effects of supraphysiological doses of levothyroxine on sleep in healthy subjects: a prospective polysomnography study.
            (Kraemer et al., 2011) Download
Disrupted sleep is prevalent in both mood and thyroid disorders. Given the emerging use of thyroid hormones in the treatment of mood disorders, we investigated the effects of supraphysiological doses of levothyroxine (L-T4) on sleep. In an open-label design, 13 healthy subjects received up to 500 μg/day for an eight-week period. A baseline night was polysomnographically recorded (PSG) followed by PSG under the maximum tolerated dose of L-T4. All subjects developed hyperthyroxinemia. The heart rate and respiration rate increased significantly with treatment; a significant increase in body temperature was observed in men but not in women. Surprisingly, treatment with supraphysiological doses of L-T4 did not cause significant effects on sleep architecture. However, the increase in body movements and REM density was close to reaching statistical significance. Here, we report on the sleep data, thyroid hormone levels, and physiological parameters during sleep. We conclude that experimentally induced hyperthyroidism does not profoundly change the sleep structure in healthy individuals underlining the good tolerability of treatment with supraphysiological doses of L-T4 in patients with mood disorders.

Prevalence of sleep abnormalities and their association among hypothyroid patients in an Indian population.
            (Krishnan et al., 2012) Download
OBJECTIVE:  To estimate the prevalence of sleep abnormalities and their association with hypothyroidism and metabolic risk factors in a relatively lean urban South Indian population. METHODS:  This population-based, cross-sectional study was carried out in the urban population of Chennai, one of the largest metropolitan cities of India. Phase 1 was conducted in the field and involved a door-to-door survey of 26,000 individuals. In phase 2, every tenth subject recruited in phase 1 (n=2600) was invited to our centre for detailed anthropometric and biochemical measurements. For the current study, a subset of 358 subjects with positive family history of hypothyroidism was randomly selected. A validated questionnaire assessing various sleep abnormalities (snoring, daytime sleepiness, lack of refreshing sleep and number of hours of sleep) was administered. Anthropometric and biochemical measurements were obtained to assess metabolic risk factors including thyroid status. RESULTS:  Snorers were more often male, older, smokers and had higher BMI, neck circumference, blood pressures, and hypothyroidism. Out of 358 patients, 133 had impaired thyroid function (37.1%) and 64 patients had both snoring and impaired thyroid function (17.8%). Subjects with daytime sleepiness had higher BMI and neck obesity. The overall prevalence of snoring and daytime sleepiness was 52% and 64%, respectively. Both sleep measures were associated with hypothyroid status. Metabolic syndrome was significantly associated with snoring even after adjusting for age, sex, family history of hypothyroidism, physical activity, smoking and alcohol. CONCLUSIONS:  The prevalence of snoring and daytime sleepiness is high among urban South Indians who are relatively lean. Both disorders are associated with hypothyroidism, although these associations were stronger in those with obesity. Based on our case prevalence and the other reports cited previously, we can reasonably conclude that thyroid screening of sleep clinic patients is essential.


Is thyroid screening of sleep clinic patients essential
            (Levy Andersen and Tufik, 2012) Download
In the article entitled ‘‘Prevalence of sleep abnormalities and their association among Hypothyroid patients in Indian popula- tion’’ published in this issue of Sleep Medicine, Vijay Krishnan et al. [1] concluded that ‘‘thyroid screening of sleep clinic patients is essential.’’ In the current framework, it is more suitable to conclude from the results that people with a predisposition or family history of hypothyroidism may have a higher prevalence of snoring, with or without clinical hypothyroidism, and thus a sleep assessment is essential. In summary, based on the valuable data provided by Vi- jay Krishnan, it seems more appropriate to state that ‘‘sleep screening of patients prone to hypothyroidism is essential’’ rather than ‘‘thyroid screening of sleep clinic patients.’’ This conclusion would fit better with the authors’ data, but, there is still much to be done to properly understand the relationship between sleep and thyroid function.

The role of thyroid hormone in sleep deprivation.
            (Pereira and Andersen, 2014) Download
Sleep deprivation is a stressful condition, as the subject experiences feelings of inadequate well-being and exhibits impairments in his/her functioning. However, in some circumstances sleep deprivation may be crucial for survival of the individual. Most likely, complex neural circuits and hormones play a role in allowing sleep deprivation to occur. For instance, thyroid hormone activity sharply increases when an individual is in a state of sleep deprivation. We believe that this increase is central to sleep deprivation physiology. During sleep deprivation, the hypothalamic-pituitary-thyroid axis initially increases as a consequence of increased release of thyroid stimulating hormone from the pituitary. Subsequently, as sleep deprivation continues, the sympathetic nervous system is recruited through its anatomical connection with the thyroid gland. While thyroid stimulating hormone levels markedly increase during sleep deprivation, it has been suggested that these increases are secondary to sleep deprivation. However, there is little evidence to support this assumption. We believe that the physiology of the thyroid axis during sleep deprivation and the actions of the effector hormone thyroid hormone suggest that thyroid hormone inhibits sleep and not the contrary. To our knowledge, few studies have addressed the possible neural functions that enable sleep deprivation. In this article, we discuss the hypothesis that an augmentation in the thyroid hormone axis is central to a subject's ability to curtail sleep.


Sleep deprivation alters thyroid hormone economy in rats.
            (Rodrigues et al., 2015) Download
NEW FINDINGS:  What is the central question of this study? The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism in sleep-deprived and sleep-restricted rats. What is the main finding and its importance? Central hypothyroidism and high thyroxine (T4 ) to 3,5,3'-triiodothyronine (T3 ) activation in brown adipose tissue were observed following sleep deprivation. Sleep-restricted rats exhibited normal thyroid-stimulating hormone and T4 concentrations despite increased circulating T3 . Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation. Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200-250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3'-triiodothyronine (T3 ), thyroxine (T4 ) and thyroid-stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50-100%) in all sleep-deprived and sleep-restricted rats; rebound restored this parameter in only the PSD24R group. The serum TSH and T4 concentrations decreased, whereas T3 increased in both the PSD24 and PSD96 groups compared with control animals (P < 0.05). Only PSD24R and PSD96R normalized T4 and thyroid-stimulating hormone concentrations, respectively, independently of the higher circulating T3 concentrations (∼20-30%) noted in all groups compared with control animals (P < 0.05). Brown adipose tissue D2 activity increased in the PSD 24 and 96 h groups (∼10 times), and PSD24R was more effective than PSD96R at restoring basal brown adipose tissue D2 activity. Our data suggest that thyroid hormone metabolism adapts to sleep deprivation-induced hypothalamic-pituitary-thyroid alterations and increases T4 to T3 activation peripherally, thereby increasing circulating T3 in rats.


Partial sleep restriction modulates secretory activity of thyrotropic axis in healthy men.
            (Schmid et al., 2013) Download
Sleep and endocrine function are known to be closely related, but studies on the effect of moderate sleep loss on endocrine axes are still sparse. We examined the influence of partial sleep restriction for 2 days on the secretory activity of the thyrotropic axis. Fifteen healthy, normal-weight men were tested in a balanced, cross-over study. Serum concentrations of thyrotrophin (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) were monitored at 1-h intervals during a 15-h daytime period (08:00-23:00 h) following two nights of restricted sleep (bedtime 02:45-07:00 h) and two nights of regular sleep (bedtime 22:45-07:00 h), respectively. Serum concentrations of fT3 (P < 0.026) and fT4 (P = 0.089) were higher after sleep restriction than regular sleep, with a subsequent blunting of TSH concentrations in the evening hours of the sleep restriction condition (P = 0.008). These results indicate profound alterations in the secretory activity of the thyrotropic axis after 2 days of sleep restriction to ~4 h, suggesting that acute partial sleep loss impacts endocrine homeostasis, with potential consequences for health and wellbeing.

Effect of levothyroxine on prolonged nocturnal sleep time and excessive daytime somnolence in patients with idiopathic hypersomnia.
            (Shinno et al., 2011) Download
OBJECTIVE:  This study aims to examine the effect of levothyroxine, a thyroid hormone, on a prolonged nocturnal sleep and excessive daytime somnolence (EDS) in patients with idiopathic hypersomnia. METHODS:  In a prospective, open-label study, nine patients were enrolled. All subjects met criteria for idiopathic hypersomnia with long sleep time defined by the International Classification of Sleep Disorders, 2nd edition (ICSD-2). Subjects with sleep apnea syndrome, obesity or hypothyroidism were excluded. Sleep architecture and subjective daytime somnolence were estimated by polysomnography (PSG) and Epworth Sleepiness Scale (ESS), respectively. After baseline examinations, levothyroxine (25μg/day) was orally administered every day. Mean total sleep time, ESS score at baseline were compared with those after treatment (2, 4 and 8 weeks). RESULTS:  Mean age of participants was 23.8±13.7 years old. At baseline, mean total sleep time (hours) and ESS score were 12.9±0.3 and 17.8±1.4, respectively. Mean total sleep times after treatment were 9.1±0.7 and 8.5±1.0h at 4 and 8 treatment weeks, respectively. Mean ESS scores were 8.8±2.3 and 7.4±2.8 at 4 and 8 treatment weeks, respectively. One patient dropped out at the 2nd week due to poor effect. No adverse effects were noted. CONCLUSIONS:  After treatment with levothyroxine for over 4 weeks, prolonged sleep time and EDS were improved. Levothyroxine was effective for hypersomnia and well tolerated.


Alterations in hypothalamus-pituitary-adrenal/thyroid axes and gonadotropin-releasing hormone in the patients with primary insomnia: a clinical research
            (Xia et al., 2013) Download
The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes' hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman's correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the "stepwise" method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.



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