Abstract
Obstructive sleep apnea syndrome (OSAS) is a chronic condition with a high prevalence (up to 7 % of the general population) characterized by frequent episodes of upper airway collapse while sleeping. Left untreated, OSAS can cause severe complications, including systemic hypertension, cardiovascular disease, stroke, and abnormal glucose metabolism. This review aims to summarize the close links between OSAS, endocrinology, and metabolism. In patients with metabolic syndrome, OSAS is an independent risk factor for the onset of type 2 diabetes and a worsening glycemic control. The accumulation of adipose tissue in the neck and limited chest wall dynamics, hypoxia, and local micro-inflammation link visceral obesity closely with OSAS. There is now an abundance of convincing data indicating that promoting lifestyle changes, improving sleep hygiene, and adjusting diet can ameliorate both metabolic syndrome and OSAS, especially in obese patients. The incidence of OSAS in acromegaly is high, though GH treatments seem to be unrelated to the onset of apnea in GH-deficient individuals. Prospective studies have suggested an association between hypertension and OSAS because intermittent nocturnal hypoxia prompts an increase in sympathetic tone, endothelial dysfunction, and vascular inflammation: aldosterone excess may have a pathophysiological role, and some authors have reported that treating OSAS leads to a modest, but significant, reduction in blood pressure.
Similar content being viewed by others
References
Punjabi NM (2008) The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc 5:136–143. doi:10.1513/pats.200709-155MG
Randerath WJ, Verbraecken J, Andreas S et al (2011) Non-CPAP therapies in obstructive sleep apnoea. Eur Respir J 37:1000–1028. doi:10.1183/09031936.00099710
Balachandran JS, Patel SR (2014) In the clinic. Obstructive sleep apnea. Ann Intern Med 161:ITC1–ITC15. doi:10.7326/0003-4819-161-9-201411040-01005
Inzucchi SE, Bergenstal RM, Buse JB et al (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35:1364–1379. doi:10.2337/dc12-0413
Tahrani AA, Ali A, Stevens MJ (2013) Obstructive sleep apnoea and diabetes: an update. Curr Opin Pulm Med 19:631–638. doi:10.1097/MCP.0b013e3283659da5
Bonsignore MR, Borel AL, Machan E et al (2013) Sleep apnoea and metabolic dysfunction. Eur Respir Rev 22:353–364. doi:10.1183/09059180.00003413
Harada Y, Oga T, Chin K, Takegami M et al (2012) Differences in relationships among sleep apnoea, glucose level, sleep duration and sleepiness between persons with and without type 2 diabetes. J Sleep Res 21(4):410–418. doi:10.1111/j.1365-2869.2012.00997.x
Tanno S, Tanigawa T, Saito I et al (2014) Sleep-related intermittent hypoxemia and glucose intolerance: a community-based study. Sleep Med 15(10):1212–1218. doi:10.1016/j.sleep.2014.05.027
Xu J, Long YS, Gozal D et al (2009) Beta-cell death and proliferation after intermittent hypoxia: role of oxidative stress. Free Radic Biol Med 46(6):783–790. doi:10.1016/j.freeradbiomed.2008.11.026
Pamidi S, Wroblewski K, Broussard J et al (2012) Obstructive sleep apnea in young lean men: impact on insulin sensitivity and secretion. Diabetes Care 35:2384–2389
Shiba T, Maeno T, Saishin Y et al (2010) Nocturnal intermittent serious hypoxia and reoxygenation in proliferative diabetic retinopathy cases. Am J Ophthalmol 149:959–963
Trayhurn P (2013) Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 93:1–21
Lanfranco F, Motta G, Minetto MA et al (2010) Growth hormone/insulin-like growth factor-I axis in obstructive sleep apnea syndrome: an update. J Endocrinol Invest 33:192–196
Aksu O, Aydın B, Doguç DK et al (2014) The evaluation of Nesfatin-1 levels in patients with OSAS associated with metabolic syndrome. J Endocrinol Invest 38(4):463–469
West SD, Nicoll DJ, Wallace TM et al (2007) Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes. Thorax 62:969–974
Weinstock TG, Wang X, Rueschman M et al (2012) A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. Sleep 35:617–625B
Sharma SK, Agrawal S, Damodaran D et al (2011) CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med 365:2277–2286
Barbosa FR, Silva CM, Lima GA et al (2014) Prevalence of obstructive sleep apnea in patients with prolactinoma before and after treatment with dopamine agonists. Pituitary 17(5):441–449. doi:10.1007/s11102-013-0524-y
Alonso-Álvarez ML, Cordero-Guevara JA, Terán-Santos J, et al. (2014) Obstructive sleep apnea in obese community-dwelling children: the NANOS study. Sleep 37(5):943–949. doi: 10.5665/sleep.3666
Sedky K, Bennett DS, Pumariega A (2014) Prader Willi syndrome and obstructive sleep apnea: co-occurrence in the pediatric population. J Clin Sleep Med 10(4):403–409. doi:10.5664/jcsm.3616
Aycan Z, Baş VN (2014) Prader-Willi syndrome and growth hormone deficiency. J Clin Res Pediatr Endocrinol 6(2):62–67. doi:10.4274/Jcrpe.1228
Bratel T, Wennlund A, Carlstrom K et al (1999) Pituitary reactivity, androgens and catecholamines in obstructive sleep apnea. Effects of continuous positive airway pressure treatment (CPAP). Respir Med 93:1–7
Mickelson SA, Lian T, Rosenthal L et al (1999) Thyroid testing and thyroid hormone replacement in patients with sleep disordered breathing. Ear Nose Throat J 78(768–771):774–775
Resta O, Pannacciulli N, Di Gioia G et al (2004) High prevalence of previously unknown subclinical hypothyroidism in obese patients referred to a sleep clinic for sleep disordered breathing. Nutr Metab Cardiovasc Dis 14(5):248–253
Mete T, Yalcin Y, Berker D, Ciftci B et al (2013) Relationship between obstructive sleep apnea syndrome and thyroid diseases. Endocrine 44(3):723–728. doi:10.1007/s12020-013-9927-9
Lanfranco F (2013) Sleep apnea syndrome and hypothyroidism. Endocrine 44(3):551–552. doi:10.1007/s12020-013-0018-8
Colao AM, Ferone D, Marzullo P et al (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25:102–152
Peker Y, Svensson J, Hedner J et al (2006) Sleep apnoea and quality of life in growth hormone (GH)-deficient adults before and after 6 months of GH replacement therapy. Clin Endocrinol 65(1):98–105
Mian C, Ceccato F, Barollo S et al (2014) AHR over-expression in papillary thyroid carcinoma: clinical and molecular assessments in a series of Italian acromegalic patients with a long-term follow-up. PLoS One 9(7):e101560. doi:10.1371/journal.pone.0101560
Hernández-Gordillo D, Ortega-Gómez Mdel R, Galicia-Polo L et al (2012) Sleep apnea in patients with acromegaly. Frequency, characterization and positive pressure titration. Open Respir Med J 6:28–33. doi:10.2174/1874306401206010028
Vannucci L, Luciani P, Gagliardi E et al (2013) Assessment of sleep apnea syndrome in treated acromegalic patients and correlation of its severity with clinical and laboratory parameters. J Endocrinol Invest 36(4):237–242. doi:10.3275/8513
Celik O, Kadioglu P (2013) Quality of life in female patients with acromegaly. J Endocrinol Invest 36(6):412–416. doi:10.3275/8761
Chemla D, Attal P, Maione L et al (2014) Impact of successful treatment of acromegaly on overnight heart rate variability and sleep apnea. J Clin Endocrinol Metab 99(8):2925–2931. doi:10.1210/jc.2013-4288
Berg C, Wessendorf TE, Mortsch F et al (2009) Influence of disease control with pegvisomant on sleep apnoea and tongue volume in patients with active acromegaly. Eur J Endocrinol 161:829–835
Nolte W, Radisch C, Rodenbeck A et al (2002) Polysomnographic findings in five adult patients with pituitary insufficiency before and after cessation of human growth hormone replacement therapy. Clin Endocrinol 56:805–810
Salvatoni A, Veronelli E, Nosetti L et al (2009) Short-term effects of growth hormone treatment on the upper airways of non severely obese children with Prader-Willi syndrome. J Endocrinol Invest 32(7):601–605. doi:10.3275/6295
Gianotti L, Pivetti S, Lanfranco F et al (2002) Concomitant impairment of growth hormone secretion and peripheral sensitivity in obese patients with obstructive sleep apnea syndrome. J Clin Endocrinol Metab 87(11):5052–5057
Andersen ML, Alvarenga TF, Mazaro-Costa R et al (2011) The association of testosterone, sleep, and sexual function in men and women. Brain Res 1416:80–104. doi:10.1016/j.brainres.2011.07.060
Bercea R, Bercea B, Mihăescu T (2012) Association between the serum level of testosterone and other comorbidities in obstructive sleep apnea. Pneumologia 61(2):98–101
Andersen ML, Tufik S (2008) The effects of testosterone on sleep and sleep-disordered breathing in men: its bidirectional interaction with erectile function. Sleep Med Rev 12(5):365–379. doi:10.1016/j.smrv.2007.12.003
Netzer NC, Eliasson AH, Strohl KP (2003) Women with sleep apnea have lower levels of sex hormones. Sleep Breath 7(1):25–29
Celec P, Mucska I, Ostatníková D et al (2014) Testosterone and estradiol are not affected in male and female patients with obstructive sleep apnea treated with continuous positive airway pressure. J Endocrinol Invest 37(1):9–12. doi:10.1007/s40618-013-0003-3
Zhang XB, Jiang XT, Du YP et al (2014) Efficacy of continuous positive airway pressure on testosterone in men with obstructive sleep apnea: a meta-analysis. PLoS ONE 9(12):e115033. doi:10.1371/journal.pone.0115033
Gambineri A, Pelusi C, Pasquali R (2003) Testosterone levels in obese male patients with obstructive sleep apnea syndrome: relation to oxygen desaturation, body weight, fat distribution and the metabolic parameters. J Endocrinol Invest 26(6):493–498
Hoyos CM, Killick R, Yee BJ et al (2012) Effects of testosterone therapy on sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo-controlled trial. Clin Endocrinol (Oxf) 77(4):599–607. doi:10.1111/j.1365-2265.2012.04413.x
Nandalike K, Strauss T, Agarwal C et al (2011) Screening for sleep-disordered breathing and excessive daytime sleepiness in adolescent girls with polycystic ovarian syndrome. J Pediatr 159(4):591–596. doi:10.1016/j.jpeds.2011.04.027
Tasali E, Chapotot F, Leproult R et al (2011) Treatment of obstructive sleep apnea improves cardiometabolic function in young obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 96(2):365–374. doi:10.1210/jc.2010-1187
Tock L, Carneiro G, Togeiro SM et al (2014) Obstructive sleep apnea predisposes to nonalcoholic Fatty liver disease in patients with polycystic ovary syndrome. Endocr Pract 20(3):244–251. doi:10.4158/EP12366.OR
Grossman AB (2010) The diagnosis and management of central hypoadrenalism. J Clin Endocrinol Metab 95(11):4855–4863. doi:10.1210/jc.2010-0982
Carneiro G, Togeiro SM, Hayashi LF et al (2008) Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis and 24 h blood pressure in men with obstructive sleep apnea syndrome. Am J Physiol Endocrinol Metab 295:E380–E384. doi:10.1152/ajpendo.00780.2007
Karaca Z, Ismailogullari S, Korkmaz S et al (2013) Obstructive sleep apnoea syndrome is associated with relative hypocortisolemia and decreased hypothalamo-pituitary-adrenal axis response to 1 and 250 μg ACTH and glucagon stimulation tests. Sleep Med 14(2):160–164. doi:10.1016/j.sleep.2012.10.013
Tirabassi G, Boscaro M, Arnaldi G (2014) Harmful effects of functional hypercortisolism: a working hypothesis. Endocrine 46(3):370–386. doi:10.1007/s12020-013-0112-y
Vgontzas AN, Pejovic S, Zoumakis E et al (2007) Hypothalamic-pituitary-adrenal axis activity in obese men with and without sleep apnea: effects of continuous positive airway pressure therapy. J Clin Endocrinol Metab 92(11):4199–4207
Lanfranco F, Gianotti L, Pivetti S et al (2004) Obese patients with obstructive sleep apnoea syndrome show a peculiar alteration of the corticotroph but not of the thyrotroph and lactotroph function. Clin Endocrinol (Oxf). 60(1):41–48
Ceccato F, Scaroni C, Boscaro M (2015) Clinical use of pasireotide for Cushing’s disease in adults. Ther Clin Risk Manag 11:425–434. eCollection 2015. Review. PubMed PMID: 25834454
Yanovsky JA, Cutler JB (1994) Glucocorticoid action and the clinical features of Cushing’s syndrome. Endocrinol Metabol Clin N Am 23:487–509
Rosenow F, McCarthy V, Caruso AC (1998) Sleep apnoea in endocrine disease. J Sleep Res 7:3–11
Bottini P, Tantucci C (2003) Sleep apnea syndrome in endocrine diseases. Respiration 70(3):320–327
Khan A, Patel NK, O’Hearn DJ et al (2013) Resistant hypertension and obstructive sleep apnea. Int J Hypertens 2013:193010. doi:10.1155/2013/193010
Kourembanas S, Marsden PA, McQuillan LP et al (1991) Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J Clin Invest 88(3):1054–1057
Van Haute FR, Taboada GF, Corrêa LL et al (2008) Prevalence of sleep apnea and metabolic abnormalities in patients with acromegaly and analysis of cephalometric parameters by magnetic resonance imaging. Eur J Endocrinol 158(4):459–465. doi:10.1530/EJE-07-075
Calhoun DA, Jones D, Textor S et al (2008) Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation 117(25):e510–e526
Pratt-Ubunama MN, Nishizaka MK, Boedefeld RL et al (2007) Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest 131(2):453–459
Gonzaga CC, Gaddam KK, Ahmed MI et al (2010) Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension. J Clin Sleep Med 6(4):363–368
Calhoun DA, Nishizaka MK, Zaman MA et al (2004) Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea. Chest 125(1):112–117
Hoy LJ, Emery M, Wedzicha JA et al (2004) Obstructive sleep apnea presenting as pseudopheochromocytoma: a case report. J Clin Endocrinol Metab 89(5):2033–2038
Arnett TR (2010) Acidosis, hypoxia and bone. Arch Biochem Biophys 503(1):103–109. doi:10.1016/j.abb.2010.07.021
Mete T, Yalcin Y, Berker D et al (2013) Obstructive sleep apnea syndrome and its association with vitamin D deficiency. J Endocrinol Invest 36(9):681–685. doi:10.3275/8923
Chen YL, Weng SF, Shen YC et al (2014) Obstructive sleep apnea and risk of osteoporosis: a population-based cohort study in Taiwan. J Clin Endocrinol Metab 99(7):2441–2447. doi:10.1210/jc.2014-1718
Bozkurt NC, Cakal E, Sahin M et al (2012) The relation of serum 25-hydroxyvitamin-D levels with severity of obstructive sleep apnea and glucose metabolism abnormalities. Endocrine 41(3):518–525. doi:10.1007/s12020-012-9595-1
Erden ES, Genc S, Motor S et al (2014) Investigation of serum bisphenol A, vitamin D, and parathyroid hormone levels in patients with obstructive sleep apnea syndrome. Endocrine 45(2):311–318. doi:10.1007/s12020-013-0022-z
Epstein LJ, Kristo D, Strollo PJ Jr et al (2009) Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med 5(3):263–276
Randerath WJ, Verbraecken J, Andreas S et al (2011) Non-CPAP therapies in obstructive sleep apnoea. Eur Respir J 37(5):1000–1028. doi:10.1183/09031936.00099710
Gay P, Weaver T, Loube D et al (2006) Evaluation of positive airway pressure treatment for sleep related breathing disorders in adults. Sleep 29:381–401
Jeong JH, Guilleminault C, Park CS et al (2014) Changes in salivary cortisol levels in pediatric patients with obstructive sleep apnea syndrome after adenotonsillectomy. Sleep Med 15(6):672–676. doi:10.1016/j.sleep.2013.12.019
Barnes M, McEvoy RD, Banks S et al (2004) Efficacy of positive airway pressure and oral appliance in mild to moderate obstructive sleep apnea. Am J Respir Crit Care Med 170:656–664
Ferguson KA, Ono T, Lowe AA et al (1996) A randomized crossover study of an oral appliance vs nasal-continuous positive airway pressure in the treatment of mild-moderate obstructive sleep apnea. Chest 109:1269–1275
Randerath WJ, Heise M, Hinz R et al (2002) An individually adjustable oral appliance vs continuous positive airway pressure in mild-to-moderate obstructive sleep apnea syndrome. Chest 122:569–575
Tan YK, L’Estrange PR, Luo YM et al (2002) Mandibular advancement splints and continuous positive airway pressure in patients with obstructive sleep apnoea: a randomized cross-over trial. Eur J Orthod 24:239–249
Gagnadoux F, Fleury B, Vielle B et al (2009) Titrated mandibular advancement versus positive airway pressure for sleep apnoea. Eur Respir J 34:914–920
Coruzzi P, Gualerzi M, Bernkopf E et al (2006) Autonomic cardiac modulation in obstructive sleep apnea: effect of an oral jaw-positioning appliance. Chest 130(5):1362–1368
Acknowledgments
The authors are grateful to Prof. O. Bruni for critically revising the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of interest to declare, nor any financial interests to disclose.
Ethical and informed consent
For Ethical Approval and Informed consent we refer to the original works that are presented in this review. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Rights and permissions
About this article
Cite this article
Ceccato, F., Bernkopf, E. & Scaroni, C. Sleep apnea syndrome in endocrine clinics. J Endocrinol Invest 38, 827–834 (2015). https://doi.org/10.1007/s40618-015-0338-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-015-0338-z