Цель исследования. Оценить распространенность и факторы риска нарушений дыхания во сне у больных акромегалией, проживающих в Московской области. Материалы и методы. Кардиореспираторное мониторирование выполнено 55 больным акромегалией (18 мужчин и 37 женщин): 27 больным с впервые выявленным заболеванием, 28 больным на фоне лечения акромегалии (из них 18 человек с неконтролируемой и 10 – с контролируемой акромегалией). Все подгруппы не различались по полу, индексу массы тела (ИМТ) и возрасту. Суточное (24-часовое) мониторирование артериального давления проведено 39 больным (12 мужчин и 27 женщин; из них у 14 пациентов акромегалия впервые выявлена, у 15 отмечался частичный и у 10 – полный контроль акромегалии на фоне проводимого лечения). Результаты и обсуждение. Обнаружена высокая распространенность нарушений дыхания во сне и у больных с впервые выявленным заболеванием, а также на фоне недостаточно эффективного лечения и при достижении контроля над акромегалией (92,6; 83,5 и 70% соответственно). Наиболее часто выявлялись нарушения дыхания во сне тяжелой и среднетяжелой степени (78,8; 72,2 и 60% соответственно). У пациентов с впервые выявленной и неконтролируемой акромегалией существенно не различались медианы показателей индекса апноэ-гипопноэ (ИАГ; 31 и 38,5 соответственно), число эпизодов апноэ за период исследования (76 и 72 соответственно) и уровень сатурации (93 и 93,5% соответственно), в то время как у пациентов с контролируемой акромегалией эти параметры улучшались (ИАГ – 20, эпизодов апноэ – 45,5 и сатурация – 95%). Пик десатурации ниже физиологического у 91,7; 86,7 и 77,8% больных с впервые выявленной, неконтролируемой и контролируемой акромегалией соответственно. Тяжесть нарушений дыхания во сне не зависела от степени повышения уровня соматотропного гормона и инсулиноподобного ростового фактора 1-го типа, а также длительности акромегалии. При акромегалии сохраняют свое значение такие общепопуляционные факторы риска нарушений дыхания во сне, как ИМТ и возраст, однако не имеет значения пол пациента. Нарушения дыхания во сне ассоциировались с отсутствием физиологического снижения систолического и диастолического артериального давления в ночное время. Заключение. Акромегалия per se является фактором риска нарушений дыхания во сне. Высокая распространенность нарушений дыхания во сне у больных акромегалией даже после достижения контроля над заболеванием свидетельствует о необходимости специализированного лечения этих нарушений.
Ключевые слова: нарушения дыхания по сне, акромегалия, индекс апноэ-гипопноэ, артериальная гипертензия, сатурация, десатурация.
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Aim. Assessment of prevalence and risk factors of sleep breathing disorders in patients with acromegaly from Moscow region. Materials and methods. Cardiorespiratory monitoring was executed to 55 patients with acromegaly (18 men and 37 women): 27 patients with de novo disease, 28 patients on treatment of acromegaly (including 18 patietns with uncontrolled and 10 – with controlled acromegaly). All subgroups did not differ on sex, BMI and age. Also 24-hour monitoring of arterial blood pressure was carried out in 39 patients (12 men and 27 women, 14 patients with de novo acromegaly, 15 and 10 patients with uncontrolled and controlled acromegaly, respectively). Results and discussion. The high prevalence of sleep breathing disorders (SBD) was revealed in patients with acromegaly from Moscow Region. SBD was found in 92.6%, 83.5% and 70.0% patients with newly diagnosed, uncontrolled and controlled acromegaly, respectively. The majority of patients had severe/moderate SBD in all subgroups (78.8%, 72.2% and 60.0%, respectively). In patients with newly diagnosed and uncontrolled acromegaly index of apnea-hypopnea (31 and 38.5 respectively), number of apnoe episodes (76 and 72) and saturation level (93% and 93.5%) did not differ significantly while these parameters were better in patients with a controlled acromegaly (apnea-hypopnea index 20, apnea episodes 45.5 and saturation level 95%). The peak of desaturation was subphysiological in 91.7%, 86.7% and 77.8% of patients with newly diagnosed, uncontrolled and controlled acromegaly, respectively. Severity of SBD did not depend on GH and IGF-1 levels as well as acromegaly duration. Such all-population risk factors of SBD as BMI and age were valuable for patients with acromegaly, however gender did not matter. SBD were associated with lack of physiological decrease of systolic and diastolic night BP. Conclusion. Acromegaly per se is a strong risk factor of sleep breathing disorders. The high prevalence of sleep breathing disorders in patients with acromegaly even after achievement of control over a disease emphasized need of specialized treatment of these violations.
1. Молитвословова Н.Н. Акромегалия. В кн.: Дедов И.И., Мельниченко Г.А., редакторы. Эндокринология. Национальное руководство. Москва: ГЭОТАР-Медиа; 2016. С. 766-777 [Molitvoslovova NN. Acromegaly. In: Dedov II, Melnichenko GA, editors. Endokrinologiya. Natsional'noe rukovodstvo [Endocrinology. National guidelines]. Moscow: GEOTAR-Media; 2016. P. 766-777 (In Russ.)].
2. Abreu A, Tovar AP, Castellanos R, Valenzuela A, Giraldo CM, Pinedo AC, Guerrero DP, Barrera CA, Franco HI, Ribeiro-Oliveira A Jr, Vilar L, Jallad RS, Duarte FG, Gadelha M, Boguszewski CL, Abucham J, Naves LA, Musolino NR, de Faria ME, Rossato C, Bronstein MD. Challenges in the diagnosis and management of acromegaly: a focus on comorbidities. Pituitary. 2016 Aug;19(4):448-457. doi: 10.1007/s11102-016-0725-2
3. Attal P, Chanson P. Endocrine Aspects of Obstructive Sleep Apnea. J Clin Endocrinol Metab. 2010;95(2):483-495. doi: 10.1210/jc.2009-1912
4. Ceccato F, Bernkopf E, Scaroni C. Sleep apnea syndrome in endocrine clinics. J Endocrinol Invest. 2015 Aug;38(8):827-834. doi: 10.1007/s40618-015-0338-z
5. Senaratna CV, Perret JL, Lodge C, Lowe A, Campbell BE, Matheson MC, Hamilton GS, Dharmage SC. Prevalence of Obstructive Sleep Apnea in the general population: A systematic review. Sleep Med Rev. 2017 Aug;34:70-81. doi: 10.1016/j.smrv.2016.07.002
6. Цой У.А., Коростовцева Л.С., Свиряев Ю.В., Семенов А.П., Ваулина Д.А., Кравченко С.О., Конради А.О., Гринева Е.Н. Распространенность нарушений дыхания во сне у больных с впервые выявленной акромегалией. Альманах клинической медицины. 2014 (32):36-42 [Tsoy UA, Korostovtseva LS, Sviryaev YuV, Semenov AP, Vaulina DA, Kravchenko SO, Konradi AO, Grineva EN. Prevalence of sleep disordered breathing in patients with newly diagnosed acromegaly. Al'manakh Klinicheskoi Meditsiny = Almanac of Clinical Medicine. 2014;32:36-42 (In Russ.)]. doi: 10.18786/2072-0505-2014-32-36-42
7. Davì MV, Dalle Carbonare L, Giustina A, et al. Sleep apnoea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease. Eur J Endocrinol. 2008;159:533-540. doi: 10.1530/EJE-08-0442
8. Pivonello R, Auriemma RS, Grasso LF, Pivonello C, Simeoli C, Patalano R, Galdiero M, Colao A. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary. 2017 Feb;20(1):46-62. doi: 10.1007/s11102-017-0797-7
9. Powlson AS, Gurnell M. Cardiovascular Disease and Sleep-Disordered Breathing in Acromegaly. Neuroendocrinology. 2016;103(1):75-85. doi: 10.1159/ 000438903
10. Somers VK, White DP, Amin R, et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation scientific statement from the American Heart Association council for high blood pressure research professional education committee, Council on clinical cardiology, Stroke council, and Council on cardiovascular nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation. 2008;118(10):1080-1111. doi: 10.1161/Circulationaha.107.189375
11. Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An AmericanAcademy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017 Mar 15;13(3):479-504. doi: 10.5664/jcsm.6506
12. Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, Amodeo C, Bortolotto LA, Krieger EM, Bradley TD, Lorenzi-Filho G. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011 Nov;58(5):811-817. doi: 10.1161/Hypertensionaha.111.179788
13. Muxfeldt ES, Margallo VS, Guimarães GM, Salles GF. Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. Am J Hypertens. 2014 Aug;27(8):1069-1078. doi: 10.1093/ajh/hpu023
14. Tolis G, Angelopoulos NG, Katounda E, et al. Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs. Neuroendocrinology. 2006;83:249-257. doi: 10.1159/000095535
15. Цой У.А., Свиряев Ю.В., Коростовцева Л.С., Семенов А.П., Ваулина Д.А., Непран В.И., Кравченко С.О., Конради А.О., Гринева Е.Н. Клинические особенности синдрома нарушения дыхания во сне у больных акромегалией. Терапевтический архив. 2015;(4):47-52 [Tsoy UA, Sviryaev YuV, Korostovtseva LS, Semenov AP, Vaulina DA, Nepran VI, Kravchenko SO, Konradi AO, Grineva EN. Clinical features of obstructive sleep apnea syndrome in patients with acromegaly. Terapevticheskiy Arkhiv = Therapeutic Archive. 2015;(4):47-52 (In Russ.)]. doi: 10.17116/terarkh201587447-52
16. Berg C, Wessendorf TE, Mortsch F, Forsting M, Teschler H, Weischer T, Mann K, Saller B, Herrmann BL. Influence of disease control with pegvisomant on sleep apnoea and tongue volume in patients with active acromegaly. Eur J Endocrinol. 2009;161:829-835. doi: 10.1530/EJE-09-0694
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1. [Molitvoslovova NN. Acromegaly. In: Dedov II, Melnichenko GA, editors. Endokrinologiya. Natsional'noe rukovodstvo [Endocrinology. National guidelines]. Moscow: GEOTAR-Media; 2016. P. 766-777 (In Russ.)].
2. Abreu A, Tovar AP, Castellanos R, Valenzuela A, Giraldo CM, Pinedo AC, Guerrero DP, Barrera CA, Franco HI, Ribeiro-Oliveira A Jr, Vilar L, Jallad RS, Duarte FG, Gadelha M, Boguszewski CL, Abucham J, Naves LA, Musolino NR, de Faria ME, Rossato C, Bronstein MD. Challenges in the diagnosis and management of acromegaly: a focus on comorbidities. Pituitary. 2016 Aug;19(4):448-457. doi: 10.1007/s11102-016-0725-2
3. Attal P, Chanson P. Endocrine Aspects of Obstructive Sleep Apnea. J Clin Endocrinol Metab. 2010;95(2):483-495. doi: 10.1210/jc.2009-1912
4. Ceccato F, Bernkopf E, Scaroni C. Sleep apnea syndrome in endocrine clinics. J Endocrinol Invest. 2015 Aug;38(8):827-834. doi: 10.1007/s40618-015-0338-z
5. Senaratna CV, Perret JL, Lodge C, Lowe A, Campbell BE, Matheson MC, Hamilton GS, Dharmage SC. Prevalence of Obstructive Sleep Apnea in the general population: A systematic review. Sleep Med Rev. 2017 Aug;34:70-81. doi: 10.1016/j.smrv.2016.07.002
6. [Tsoy UA, Korostovtseva LS, Sviryaev YuV, Semenov AP, Vaulina DA, Kravchenko SO, Konradi AO, Grineva EN. Prevalence of sleep disordered breathing in patients with newly diagnosed acromegaly. Al'manakh Klinicheskoi Meditsiny = Almanac of Clinical Medicine. 2014;32:36-42 (In Russ.)]. doi: 10.18786/2072-0505-2014-32-36-42
7. Davì MV, Dalle Carbonare L, Giustina A, et al. Sleep apnoea syndrome is highly prevalent in acromegaly and only partially reversible after biochemical control of the disease. Eur J Endocrinol. 2008;159:533-540. doi: 10.1530/EJE-08-0442
8. Pivonello R, Auriemma RS, Grasso LF, Pivonello C, Simeoli C, Patalano R, Galdiero M, Colao A. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary. 2017 Feb;20(1):46-62. doi: 10.1007/s11102-017-0797-7
9. Powlson AS, Gurnell M. Cardiovascular Disease and Sleep-Disordered Breathing in Acromegaly. Neuroendocrinology. 2016;103(1):75-85. doi: 10.1159/ 000438903
10. Somers VK, White DP, Amin R, et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation scientific statement from the American Heart Association council for high blood pressure research professional education committee, Council on clinical cardiology, Stroke council, and Council on cardiovascular nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation. 2008;118(10):1080-1111. doi: 10.1161/Circulationaha.107.189375
11. Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An AmericanAcademy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017 Mar 15;13(3):479-504. doi: 10.5664/jcsm.6506
12. Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, Amodeo C, Bortolotto LA, Krieger EM, Bradley TD, Lorenzi-Filho G. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011 Nov;58(5):811-817. doi: 10.1161/Hypertensionaha.111.179788
13. Muxfeldt ES, Margallo VS, Guimarães GM, Salles GF. Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. Am J Hypertens. 2014 Aug;27(8):1069-1078. doi: 10.1093/ajh/hpu023
14. Tolis G, Angelopoulos NG, Katounda E, et al. Medical treatment of acromegaly: comorbidities and their reversibility by somatostatin analogs. Neuroendocrinology. 2006;83:249-257. doi: 10.1159/000095535
15. [Tsoy UA, Sviryaev YuV, Korostovtseva LS, Semenov AP, Vaulina DA, Nepran VI, Kravchenko SO, Konradi AO, Grineva EN. Clinical features of obstructive sleep apnea syndrome in patients with acromegaly. Terapevticheskiy Arkhiv = Therapeutic Archive. 2015;(4):47-52 (In Russ.)]. doi: 10.17116/terarkh201587447-52
16. Berg C, Wessendorf TE, Mortsch F, Forsting M, Teschler H, Weischer T, Mann K, Saller B, Herrmann BL. Influence of disease control with pegvisomant on sleep apnoea and tongue volume in patients with active acromegaly. Eur J Endocrinol. 2009;161:829-835. doi: 10.1530/EJE-09-0694
1 ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского», Москва, Россия;
2 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия
1 Moscow Regional Research and Clinical Institute («MONIKI»), Moscow, Russia;
2 A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia