Hypothalamic-Pituitary-Adrenal Axis Activation in Obstructive Sleep Apnea: The Effect of Continuous Positive Airway Pressure Therapy

Henley, David; Russell, Georgina; Douthwaite, J. A.; Wood, Susan A.; Buchanan, Fiona; Gibson, Rosemary; Woltersdorf, Wolfram; Catterall, J R; Lightman, Stafford L.

doi:10.1210/jc.2009-1174

Cited by 112 publications

(83 citation statements)

References 48 publications

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“…The previous reports including Carneiro's study were that the effect of CPAP therapy for the HPA axis in OSAS patients was examined three months after CPAP therapy [11,[21][22][23]. On the other hand we performed 0.5 mg DST for them within a few but not with AHI (p=0.784), BMI (p=0.984), waist circumference (p=0.967), HbA1c (p=0.261), fasting plasma glucose (p=0.420) or HOMA-IR (p=0.500).…”

Section: Discussionmentioning

confidence: 99%

Obstructive sleep apnea syndrome causes a pseudo-Cushing’s state in Japanese obese patients with type 2 diabetes mellitus

et al. 2013

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OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) is associated with increased risk of hypertension, diabetes mellitus, myocardial infarction, congestive heart failure, and stroke [1,2]. Continuous positive airway pressure (CPAP) therapy improves not only upper airway patency but also the quality of life and reduces the frequency of OSAS-related cardiovascular complications [2][3][4].The underlying mechanisms of the multi-organ complications associated with OSAS are considered to include repetitive upper airway obstruction, hypoxemia and sleep fragmentation. These abnormalities likely result in various neural and metabolic changes, Abstract. Activation of the hypothalamic-pituitary-adrenal axis has been reported in some patients with the obstructive sleep apnea syndrome (OSAS). In current study, we investigated whether OSAS affect the screening test for subclinical Cushing's disease using 0.5 mg overnight dexamethasone suppression test (DST) in Japanese obese diabetic patients with OSAS. Among Japanese obese patients with type 2 diabetes mellitus who had been hospitalized in our department, we selected 20 patients with moderate to severe untreated OSAS (apnea-hypoxia index, AHI, of ≥15 events/hour). All patients underwent 0.5 mg DST. The same test was repeated in patients with positive response of it within a few days after continuous positive airway pressure (CPAP) therapy. We found that five patients showed positive response of DST (25%). Three of these patients continued to use CPAP, and they showed normal response of DST after CPAP therapy. Serum cortisol after 0.5 mg DST measured before CPAP therapy correlated significantly with fasting serum cortisol level (r=0.764, p<0.0001), but not with various clinical parameters, including AHI (p=0.784), body mass index (p=0.984), waist circumference (p=0.957), HbA1c (p=0.261), fasting plasma glucose (p=0.420) and HOMA-IR (p=0.500). Our study show that OSAS causes a pseudo-Cushing's syndrome in obese patients with type 2 diabetes mellitus, which phenomena can be reversed by CPAP therapy.

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Section: Discussionmentioning

confidence: 99%

Obstructive sleep apnea syndrome causes a pseudo-Cushing’s state in Japanese obese patients with type 2 diabetes mellitus

et al. 2013

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“…Furthermore, consistent with changes in the pulsatile pattern observed in a number of disease models in the rat (e.g., chronic inflammation and chronic exposure to constant light), a similar disruption of cortisol pulsatility has been reported in chronic illness in humans. For example, an elevation in CORT secretion due to an increase in the mass of CORT pulses has been observed in patients affected by obstructive sleep apnea, and a complete remission of these hormonal changes was achieved following medical treatment of the condition (Henley et al 2009b).…”

Section: Ultradian Rhythm Of Glucocorticoids In Human Disease and Crimentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Spiga¹,

Walker²,

Gupta³

et al. 2015

Journal of Endocrinology

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A pulsatile pattern of secretion is a characteristic of many hormonal systems, including the glucocorticoid-producing hypothalamic-pituitary-adrenal (HPA) axis. Despite recent evidence supporting its importance for behavioral, neuroendocrine and transcriptional effects of glucocorticoids, there has been a paucity of information regarding the origin of glucocorticoid pulsatility. In this review we discuss the mechanisms regulating pulsatile dynamics of the HPA axis, and how these dynamics become disrupted in disease. Our recent mathematical, experimental and clinical studies show that glucocorticoid pulsatility can be generated and maintained by dynamic processes at the level of the pituitary-adrenal axis, and that an intra-adrenal negative feedback may contribute to these dynamics.

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“…Given the above limitations, it is no surprise that studies on the effects of continuous positive airway pressure (CPAP) treatment on HPA axis activity have yielded inconsistent findings [8,10,11,[13][14][15][16][17]. In addition, most of the CPAP studies have been confounded by methodological limitations such as lack of a control group at baseline, or a placebo control group, as well as a small sample size.…”

Section: Introductionmentioning

confidence: 99%

Sleep apnoea and the hypothalamic–pituitary–adrenal axis in men and women: effects of continuous positive airway pressure

et al. 2015

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Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic-pituitary-adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use.72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment.In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls.These results suggest that OSA in nonobese men and slightly obese women is associated with HPA axis activation, similar albeit stronger compared with obese individuals with sleep apnoea. Short-term CPAP use decreased cortisol levels significantly compared with baseline, indicating that CPAP may have a protective effect against comorbidities frequently associated with chronic activation of the HPA axis, e.g. hypertension.@ERSpublications OSA in nonobese men/slightly obese women is associated with HPA axis activation and CPAP lowers HPA axis activity http://ow.ly/Stn94

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Hypothalamic-Pituitary-Adrenal Axis Activation in Obstructive Sleep Apnea: The Effect of Continuous Positive Airway Pressure Therapy

Abstract: Untreated compared to treated OSA is associated with marked disturbances in ACTH and cortisol secretory dynamics, resulting in prolonged tissue exposure to disordered, elevated hormone levels.

Cited by 112 publications

References 48 publications

Obstructive sleep apnea syndrome causes a pseudo-Cushing’s state in Japanese obese patients with type 2 diabetes mellitus

Obstructive sleep apnea syndrome causes a pseudo-Cushing’s state in Japanese obese patients with type 2 diabetes mellitus

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Sleep apnoea and the hypothalamic–pituitary–adrenal axis in men and women: effects of continuous positive airway pressure

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