Adrenal gland size in obstructive sleep apnea: Morphological assessment of hypothalamic pituitary adrenal axis activity.

Kiminobu Tanizawa,Kimihiko Murase,Takuma Minami,Tomohiro Handa,Andrea Romigi,Toyohiro Hirai,Takeshi Matsumoto,Kazuo Chin,Morito Inouchi,Toru Oga,Ryo Tachikawa

doi:10.1371/journal.pone.0222592

Abstract

ObjectivesThe association of obstructive sleep apnea (OSA) with hypothalamic pituitary adrenal (HPA) axis activation has not been fully understood from results of previous studies using hormonal assessments. We aimed to investigate the relationship between adrenal size, a potential marker reflecting HPA axis activity, and sleep parameters related to OSA.MethodsWe retrospectively reviewed data on 284 consecutive adult patients aged 20 to 80 y who had undergone polysomnography and abdominal computed tomography (CT). OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 75), moderate (AHI 15 to 30, n = 80), and severe OSA (AHI ≥30, n = 129). Widths of adrenal body and limbs were measured by abdominal CT.ResultsAdrenal size was greater in participants with severe OSA than in those with none/mild or moderate OSA (adrenal body width: 6.03 mm, none/mild OSA; 6.09 mm, moderate OSA; 6.78 mm, severe OSA; p <0.001; adrenal limb width: 3.75 mm, none/mild OSA; 3.95 mm, moderate OSA; 4.26 mm, severe OSA, p <0.001). Multivariate regression analysis showed that not the 3% oxygen desaturation index and time of SpO2 <90% but a higher arousal index was the only determinant factor for increased adrenal limb width (β = 0.27, p <0.001) after adjusting for other variables that could affect adrenal size. Neither the arousal index nor hypoxic parameters were associated with adrenal body width.ConclusionsResults indicated that adrenal glands may enlarge in response to longstanding sleep fragmentation, suggesting the involvement of OSA in HPA axis augmentation.

Highlights

Obstructive sleep apnea (OSA) is a prevalent sleep disordered breathing condition characterized by repetitive partial or complete upper airway obstruction during sleep
Multivariate regression analysis showed that not the 3% oxygen desaturation index and time of SpO2
Results indicated that adrenal glands may enlarge in response to longstanding sleep fragmentation, suggesting the involvement of OSA in hypothalamic pituitary adrenal (HPA) axis augmentation

Summary

Introduction

Obstructive sleep apnea (OSA) is a prevalent sleep disordered breathing condition characterized by repetitive partial or complete upper airway obstruction during sleep. Intermittent hypoxia and sleep fragmentation are the major pathophysiological consequences of OSA that induce sympathetic nervous hyperactivity, oxidative stress, and systemic inflammation, leading to metabolic and cardiovascular comorbidities [1,2]. OSA-induced hypoxia and sleep fragmentation are considered to be stressors that may activate human stress systems consisting of the sympathetic nervous system and hypothalamic pituitary adrenal (HPA) axis. The activation of stress systems in OSA has been well demonstrated in the sympathetic nervous system and may contribute to the development of comorbidities [3]. Studies demonstrating that elevated cortisol levels in OSA patients might support a temporal association between OSA and HPA axis activation [5,6], those findings do not necessarily reflect accumulated effects of OSA as a stressor. Which sleep index in OSA that serves as a strong physiological stressor to activate the HPA axis has not been identified

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Conclusion