Hypothalamic-Pituitary-Adrenal Axis Activity in Obese Men with and without Sleep Apnea: Effects of Continuous Positive Airway Pressure Therapy

Vgontzas, Alexandros N.; Pejovic, Slobodanka; Zoumakis, Emmanouil; Lin, Hung Mo; Bentley, Christy; Bixler, Edward O.; Sarrigiannidis, A.; Basta, Maria; Chrousos, George P.

doi:10.1210/jc.2007-0774

Cited by 125 publications

(135 citation statements)

References 38 publications

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“…The same study also demonstrated that the cortisol increases to Cortrosyn or insulin were similar in the obese and controls. Administration of CRH to obese men with or without sleep apnea syndrome resulted in amplified ACTH release compared with lean controls, but cortisol secretion was not greater (32). Finally, insulin-induced hypoglycemia caused a larger ACTH increase in obese subjects than that in controls, both in the morning and evening, but the cortisol response in obese subjects was diminished in obesity (33).…”

Section: Discussionmentioning

confidence: 83%

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Roelfsema

Pijl

Keenan

et al. 2012

European Journal of Endocrinology

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Background: The ACTH-cortisol axis in women is activated and associated with decreased ACTH potency, estimated by relating ACTH and cortisol pulse masses. Recently, a new accurate method for constructing the endogenous dose-response relationship was introduced, which is based on the relation between ACTH concentrations and associated cortisol secretion rates within cortisol bursts. Hypothesis: The endogenous dose-response relation between ACTH and cortisol in obesity is changed, leading to diminished responsiveness. Subjects: Twenty-five obese premenopausal women and 16 normal weight premenopausal women were studied by 10-min blood sampling for 24 h. Outcomes: ACTH and cortisol secretion rates, analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were quantified. Results: The initial potency (negative logarithm) was K7.83G0.75 (meanGS.E.M.) in obese women and K10.14G1.08 in lean women (PZ0.10), and the corresponding values for the recovery phase were K26.62G2.21 and K36.67G1.66 (PZ0.004). The sensitivity (curve slope) amounted to 0.468G0.05 in obese women and 0.784G0.09 in normal weight women (PZ0.004). The efficacy (maximal value) was 17.6G4.9 nmol/l per min in obese women and 26.3G3.8 nmol/l per min in normal weight women (PZ0.009). Basal secretion rate, inflection point, and EC 50 values were not different. Bromocriptine or acipimox did not change the dose-response curve. Conclusion: The ACTH-cortisol relation in obesity in women is characterized by decreased sensitivity and efficacy, thus explaining non-elevated serum cortisol concentrations despite increased plasma ACTH levels.

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Section: Discussionmentioning

confidence: 83%

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Roelfsema

Pijl

Keenan

et al. 2012

European Journal of Endocrinology

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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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“…The associated hypoxaemia and the concomitant increase in arterial carbon dioxide tension are expected to result in sympathetic activation and catecholamine secretion, while the repeated arousals can cause activation of the hypothalamic-pituitary-adrenal (HPA) axis, thus increasing cortisol release [2]. However, and contrary to what was expected, most studies have reported no significant association [3][4][5][6][7][8] or decreased HPA axis activity [9], whereas only two studies reported increased HPA axis activity in sleep apnoea patients compared with controls [10,11]. A more recent study [12] found a significant association between apnoea severity and 24-h cortisol values; however, it was limited by the absence of a control group.…”

Section: Introductionmentioning

confidence: 96%

“…Obesity is the strongest risk factor for sleep apnoea, but also a known HPA axis modulator, and thus a possible confounder of the association between sleep apnoea and HPA axis activity [11].…”

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 Activity in Obese Men with and without Sleep Apnea: Effects of Continuous Positive Airway Pressure Therapy

Cited by 125 publications

References 38 publications

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

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

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

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