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УДК: 616.8-007.41 DOI:10.33920/med-01-2010-08

Современные принципы диагностики и консервативного лечения болезни Иценко — Кушинга

Абдали А. ФГАУ «Национальный медицинский исследовательский центр нейрохирургии имени Н. Н. Бурденко» Министерства здравоохранения Российской Федерации, ул. 4-я Тверская-Ямская, 16, Москва, ORCID: 0000-0003-4475-6590
Астафьева Л. И. ФГАУ «Национальный медицинский исследовательский центр нейрохирургии имени Н. Н. Бурденко» Министерства здравоохранения Российской Федерации, ул. 4-я Тверская-Ямская, 16, Москва, ORCID: 0000-0003-4480-1902
Калинин П. Л. ФГАУ «Национальный медицинский исследовательский центр нейрохирургии имени Н. Н. Бурденко» Министерства здравоохранения Российской Федерации, ул. 4-я Тверская-Ямская, 16, Москва, ORCID: 0000-0001-9333-9473
Трунин Ю. Ю. ФГАУ «Национальный медицинский исследовательский центр нейрохирургии имени Н. Н. Бурденко» Министерства здравоохранения Российской Федерации, ул. 4-я Тверская-Ямская, 16, Москва, ORCID iD: 0000-0002-4240-5036
Чернов И. В. «Национальный медицинский исследовательский центр нейрохирургии имени Н. Н. Бурденко» Министерства здравоохранения Российской Федерации, ул. 4-я Тверская-Ямская, 16, Москва, ORCID: 0000-0002-9789-3452
Чмутин Г. Е. доктор медицинских наук, профессор, зав. кафедрой неврологии с курсом нейрохирургии Медицинского института ФГАОУ ВО «Российский университет дружбы народов», Москва, ORCID: 0000-0002-3323-508X
Бадщах Зар Абдали Российский университет дружбы народов, кафедра нервных болезней и нейрохирургии, ул. Миклухо-Маклая, 6, Москва, ORCID: 0000-0002-8960-8287
Гул Шариф Ш. Российский университет дружбы народов, кафедра нервных болезней и нейрохирургии, ул. Миклухо-Маклая, 6, Москва, ORCID: 0000-0003-3036-3681
Симфукве К. Российский университет дружбы народов, кафедра нервных болезней и нейрохирургии, ул. Миклухо-Маклая, 6, Москва, ORCID: 0000-0003-3611-3720

Болезнь Иценко — Кушинга — тяжелое нейроэндокринное заболевание, вызванное в большинстве случаев гиперсекрецией адренокортикотропного гормона доброкачественной опухолью гипофиза и сопровождающееся клиническими симптомами гиперкортицизма. Болезнь Иценко — Кушинга связана с повышенным риском сердечно-сосудистых и метаболических нарушений, психических осложнений, остеопороза и инфекционных заболеваний, что приводит к высоким показателям смертности. Целью данной статьи является рассмотрение клинических, диагностических аспектов этого заболевания с использованием современных международных рекомендаций и современных принципов консервативной терапии.

Литература:

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41. Hermus A. R. et al. The corticotropin-releasing-hormone test versus the high-dose dexamethasone test in the differential diagnosis of Cushing’s syndrome. Lancet. 1986; 2 (8506): 540–4.

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1. Chaudhry H. S., Singh G. Cushing Syndrome, in StatPearls. 2019: Treasure Island (FL).

2. Acebes J. J. et al. Early post-operative ACTH and cortisol as predictors of remission in Cushing’s disease. Acta Neurochir (Wien). 2007; 149 (5): 471–7; discussion 477–9.

3. Mehta G. U., Lonser R. R., Oldfield E. H. The history of pituitary surgery for Cushing disease. J Neurosurg. 2012; 116 (2): 261–8.

4. Tjornstrand A. et al. The incidence rate of pituitary adenomas in western Sweden for the period 2001–2011. Eur J Endocrinol. 2014; 171 (4): 519–26.

5. Youmas and Winn neurological surgery elsevier,Inc. 2017; 7th edition: 1175–1179.

6. Pecori Giraldi F., M. M., Cavagnini F. Gender-related differences in the presentation and course of Cushing’s disease. J Clin Endocrinol Metab. 2003; 88: 1554–1558.

7. Ragel B. T., Couldwell W. T. Pituitary carcinoma: a review of the literature. Neurosurg Focus. 2004; 16 (4): E7.

8. Pivonello R. et al. The Treatment of Cushing’s Disease. Endocr Rev. 2015; 36 (4): 385–486.

9. Plotz C. M., K. A. R. C. The natural history of Cushing’s syndrome. American Journal of Medicine. 1952; 13: 597–614.

10. Buliman A. et al. Cushing’s disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment. J Med Life. 2016; 9 (1): 12–18.

11. A. Yu., G., Neurosurgical treatment of patients with Cushing disease and acromegaly. 2011.

12. Feelders R. A. et al. The burden of Cushing’s disease: clinical and health-related quality of life aspects. Eur J Endocrinol. 2012; 167 (3): 311–26.

13. Mancini T. et al. High cardiovascular risk in patients with Cushing’s syndrome according to 1999 WHO/ISH guidelines. Clin Endocrinol (Oxf). 2004; 61 (6): 768–77.

14. Muiesan M. L. et al. Left ventricular structural and functional characteristics in Cushing’s syndrome. J Am Coll Cardiol. 2003; 41 (12): 2275–9.

15. Fallo F. et al. Cardiovascular autonomic function in Cushing’s syndrome. J Endocrinol Invest. 2009; 32 (1): 41–5.

16. Neary N. M. et al. Hypercortisolism is associated with increased coronary arterial atherosclerosis: analysis of noninvasive coronary angiography using multidetector computerized tomography. J Clin Endocrinol Metab. 2013; 98 (5): 2045–52.

17. Faggiano A. et al. Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing’s disease during active disease and 1 year after disease remission. J Clin Endocrinol Metab. 2003; 88 (6): 2527–33.

18. Magiakou M. A., Smyrnaki P., Chrousos G. P. Hypertension in Cushing’s syndrome. Best Pract Res Clin Endocrinol Metab. 2006; 20 (3): 467–82.

19. Boscaro M. et al. Anticoagulant prophylaxis markedly reduces thromboembolic complications in Cushing’s syndrome. J Clin Endocrinol Metab. 2002; 87 (8): 3662–6.

20. Pivonello R. et al. The metabolic syndrome and cardiovascular risk in Cushing’s syndrome. Endocrinol Metab Clin North Am. 2005; 34 (2): 327–39, viii.

21. Chanson P., Salenave S. Metabolic syndrome in Cushing’s syndrome. Neuroendocrinology. 2010; 92 Suppl 1: 96–101.

22. Arnaldi G. et al. Pathophysiology of dyslipidemia in Cushing’s syndrome. Neuroendocrinology. 2010; 92 Suppl 1: 86–90.

23. Iwona J Bujalska, M., M. Sudhesh Kumar, and F. Prof Paul M Stewart. Does central obesity reflect «Cushing’s disease of the omentum»? The Lancet 349 (9060): 1210–1213.

24. Munir A., Newell-Price J. Management of diabetes mellitus in Cushing’s syndrome. Neuroendocrinology. 2010; 92 Suppl 1: 82–5.

25. Clayton R. N. Mortality in Cushing’s disease. Neuroendocrinology. 2010; 92 Suppl 1: 71–6.

26. Wu¨rzburger M. I., P. G., Brkiæ S. D., Vuckoviæ S., Pendiæ B. Cushing’s syndrome–transitory immune deficiency state. Postgrad Med J. 1986; 62: 657–659.

27. Pereira A. M., Tiemensma J., Romijn J. A. Neuropsychiatric disorders in Cushing’s syndrome. Neuroendocrinology. 2010; 92 Suppl 1: 65–70.

28. Buliman A., T. L., Paun D. L., Mirica A., Dumitrache C. Cushing’s disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment. J Med Life. 2016; 9 (1): 12–18.

29. al W. Y. e. Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas. J Clin Endocrinol Metab. (90): 4963–9.

30. Langlois F., McCartney S., Fleseriu M. Recent Progress in the Medical Therapy of Pituitary Tumors. Endocrinol Metab (Seoul). 2017; 32 (2): 162–170.

31. Newell-Price J. et al. A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing’s syndrome. Clin Endocrinol (Oxf). 1995; 43 (5): 545–50.

32. Res N.-P. J. B. P. Diagnosis/differential diagnosis of Cushing’s syndrome: a review of best practice. Clin Endocrinol Metab. 2009; Suppl 1 (23): S5–14.

33. Nieman L. K. et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008. 93 (5): 1526–40.

34. Nieman L. K., C. G. J. The sensitivity of the urine free cortisol measurement as a screening test for Cushing’s syndrome) Program of the 72nd Annual Meeting of the Endocrine Society; Atlanta, GA. Atlanta: Endocrine Society 1990, 1990 Jun. (abstract 822) (20–23): 111.

35. Elamin M. B. et al. Accuracy of diagnostic tests for Cushing’s syndrome: a systematic review and metaanalyses. J Clin Endocrinol Metab. 2008; 93 (5): 1553–62.

36. Arnaldi G., A. A., Atkinson A. B., Bertagna X., Cavagnini and C. G. F. et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003; 88: 5593–5602.

37. Newell-Price J., T. P., Besser M., Grossman A. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev. 1998: 19: 647–72.

38. Arnaldi G. et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003; 88 (12): 5593–602.

39. Chrousos G. P. et al. The corticotropin-releasing factor stimulation test. An aid in the evaluation of patients with Cushing’s syndrome. N Engl J Med. 1984; 310 (10): 622–6.

40. Nieman L. K. et al. The ovine corticotropin-releasing hormone (CRH) stimulation test is superior to the human CRH stimulation test for the diagnosis of Cushing’s disease. J Clin Endocrinol Metab. 1989; 69 (1): 165–9.

41. Hermus A. R. et al. The corticotropin-releasing-hormone test versus the high-dose dexamethasone test in the differential diagnosis of Cushing’s syndrome. Lancet. 1986; 2 (8506): 540–4.

42. Reimondo G. et al. The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing’s syndrome. Clin Endocrinol (Oxf). 2003; 58 (6): 718–24.

43. Pecori Giraldi F., I. C., Cavagnini F. Study Group ofthe Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-pituitary-adrenal axis. The corticotropin-releasing hormone test in the diagnosis of ACTHdependent Cushing’s syndrome: a reappraisal. . Clin Endocrinol (Oxf). 2001; 54: 601–7.

44. Kakade H. R. et al. Clinical, biochemical and imaging characteristics of Cushing’s macroadenomas and their long-term treatment outcome. Clin Endocrinol (Oxf). 2014; 81 (3): 336–42.

45. Lonser R. R. et al. Outcome of surgical treatment of 200 children with Cushing’s disease. J Clin Endocrinol Metab. 2013; 98 (3): 892–901.

46. Kornienko V. N., Pronin I. N. Diagnostic neuroradiology. Vol. 2. Moscow, 2009.

47. Bashari W. A. et al. Modern imaging of pituitary adenomas. Best Pract Res Clin Endocrinol Metab. 2019; 33 (2): 101278.

48. Masopust V. et al. Magnetic resonance imaging and histology correlation in Cushing’s disease. Neurol Neurochir Pol. 2017; 51 (1): 45–52.

49. Kunii N. et al. Rathke’s cleft cysts: differentiation from other cystic lesions in the pituitary fossa by use of single-shot fast spin-echo diffusion-weighted MR imaging. Acta Neurochir (Wien). 2007; 149 (8): 759–69; discussion 769.

50. Hassan H. A. et al. Diagnostic value of early postoperative MRI and diffusion-weighted imaging following trans-sphenoidal resection of non-functioning pituitary macroadenomas. Clin Radiol. 2018; 73 (6): 535–541.

51. Buttrick S. et al. Extradural clinoidectomy for resection of clinoidal meningioma. Neurosurg Focus. 2017; 43 (VideoSuppl2): V10.

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Болезнь Иценко — Кушинга (БИК) — тяжелое нейроэндокринное заболевание, вызванное гиперсекрецией адренокортикотропного гормона (АКТГ) доброкачественной опухолью гипофиза (кортикотропиномой) или, в редких случаях, карциномой гипофиза [1]. БИК является достаточно редким заболеванием: на его долю приходится 4–8% всех гормонально активных опухолей гипофиза [2]. При этом БИК является второй по частоте (после экзогенной) причиной гиперкортицизма среди всех возможных причин последнего [3]. По оценкам различных авторов, заболеваемость БИК составляет 2,4 случая на миллион человек в год, а распространенность составляет около 40 случаев на миллион человек [2].

Женщины болеют в 2,8 раза чаще, чем мужчины, а характерным возрастом является период с 20 до 60 лет [4] Так, средний возраст постановки диагноза БИК у взрослых составляет в среднем 30 лет у женщин и 37 лет у мужчин. У детей заболевание встречается реже — кортикотропинома лишь в 30% случаев является причиной гиперкортицизма [5], и чаще всего симптомы проявляются в возрасте 10 лет [6].

Практически все кортикотропиномы являются доброкачественными (лишь 1 из 1000 способна к метастазированию) [7].

Нелеченые пациенты с БИК могут сталкиваться с тяжелыми осложнениями, вызванными гиперкортицизмом, такими как сердечно-сосудистые нарушения, сахарный диабет и инфекции. Уровень их смертности в 1,7–4 раза выше, чем у населения в целом [8] а 5-летняя выживаемость составляет лишь 50% [9], что в основном связно с тяжелыми сердечно-сосудистыми осложнениями (инфаркт миокарда и инсульт) [10].

Клиническая картина основывается на нарушении функции гипоталамо-гипофизарной оси, что было впервые описано в 1932 г. Harvey Cushing [3]. Увеличение секреции АКТГ приводит к хроническому повышению уровня кортизола и вызывает развитие эндогенного гиперкортицизма [11], что в свою очередь при длительном воздействии приводит к мультисистемной патологии, включающей поражение сердечно-сосудистой системы, метаболические нарушения, инфекционные осложнения и психические нарушения [6].

Для Цитирования:
Абдали А., Астафьева Л. И., Калинин П. Л., Трунин Ю. Ю., Чернов И. В., Чмутин Г. Е., Бадщах Зар Абдали, Гул Шариф Ш., Симфукве К., Современные принципы диагностики и консервативного лечения болезни Иценко — Кушинга. Вестник неврологии, психиатрии и нейрохирургии. 2020;10.
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