Взаимосвязь показателей кальциевого обмена и ренин-ангиотензин-альдостероновой системы при первичном гиперпаратиреозе в до- и раннем послеоперационном периодах

Все больше данных свидетельствует о наличии взаимосвязи между ренин-ангиотензин-альдостероновой системой (РААС) и параметрами кальциевого обмена. Вероятно, субклинические изменения активности отдельных компонентов РААС могут являться предикторами поражения сердечно-сосудистой системы у пациентов с первичным гиперпаратиреозом (ПГПТ). Цель исследования — изучить активность компонентов РААС и параметры кальциевого обмена у пациентов с манифестным ПГПТ и нормотонией в до- и раннем послеоперационном периодах. Материалы и методы. Проведено проспективное несравнительное исследование 35 пациентов с верифицированным диагнозом ПГПТ без сопутствующих кардиоваскулярных заболеваний и значимых факторов риска их развития, а также на фоне отсутствия приема препаратов, влияющих на кальциевый обмен и РААС. Всем пациентам на дооперационном этапе и на третьи сутки после паратиреоидэктомии были исследованы основные биохимические и гормональные показатели кальциевого обмена, а также параметры РААС. Результаты. У пациентов с ПГПТ и нормотонией корреляций уровней паратгормона и сывороточного кальция с показателями РААС как в до-, так и в послеоперационном периоде не выявлено, однако на 3-и сутки после успешной паратиреоидэктомии продемонстрировано снижение концентрации альдостерона сыворотки (p = 0,004). Заключение. Для уточнения взаимосвязей компонентов кальциевого обмена и РААС и выявления возможных предикторов развития сердечно-сосудистой патологии при ПГПТ необходимо проведение дальнейших крупных исследований с продолжительным периодом наблюдения пациентов.

первичный гиперпаратиреоз, нарушение кальциевого обмена, артериальная гипертензия, нормотония, ренин-ангиотензин-альдостероновая система, альдостерон

1. Andersson P, Rydberg E, Willenheimer R. Primary hyperparathyroidism and heart disease-a review. Eur Heart J. 2004;25(20):1776–1787. doi: 10.1016/j.ehj.2004.07.010.

2. Вороненко И. В., Мокрышева Н. Г., Рожинская Л. Я., Сыркин А. Л. Состояние сердечно-сосудистой системы при клинически выраженном и малосимптомном первичном гиперпаратиреозе. Проблемы эндокринологии. 2009;55(3):25–29. doi: 10.14341/probl200955325–29

3. Pepe J, Cipriani C, Sonato C, Raimo O, Biamonte F, Minisola S. Cardiovascular manifestations of primary hyperparathyroidism: a narrative review. Eur J Endocrinol. 2017;177(6): R297-R308. doi: 10.1530/EJE-17–0485

4. Foley RN, Collins AJ, Ishani A, Kalra PA. Calciumphosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2008;156(3):556–563. doi: 10.1016/j.ahj.2008.05.016

5. Hassan M, Qureshi W, Sroujieh LS, Albashaireh D, BouMalham S, Liroff M et al. Interplay of parathyroid hormone and aldosterone antagonist in prevention of heart failure hospitalizations in chronic kidney disease. J Renin Angiotensin Aldosterone Syst. 2014;15(3):278–285. doi: 10.1177/1470320314539180

6. Jorde R, Sundsfjord J, Fitzgerald P, Bonaa KH. Serum calcium and cardiovascular risk factors and diseases: the Tromso Study. Hypertension. 1999;34 (3):484–490

7. Kamycheva E, Sundsfjord J, Jorde R. Serum parathyroid hormone levels predict coronary heart disease: the Tromso Study. Eur J Cardiovasc Prev Rehabil 2004;11(1):69–74. doi: 10.1097/01.hjr.0000114706.27531.01

8. Larsson TE, Olauson H, Hagstrom E, Ingelsson E, Arnlov J, Lind L et al. Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community. Arterioscler Thromb Vasc Biol. 2010;30(2):333–339. doi: 10.1161/ATVBAHA.109.196675

9. Lind L, Skarfors E, Berglund L, Lithell H, Ljunghall S. Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years. J Clin Epidemiol. 1997;50(8):967–973.

10. Bianchetti MG, Beretta-Piccoli C, Weidmann P, Link L, Boehringer K, Ferrier Cet al. Calcium and blood pressure regulation in normal and hypertensive subjects. Hypertension. 1983;5(4Part2): Ii57–Ii65.

11. Gennari C, Nami R, Bianchini C, Aversa AM. Blood pressure effects of acute hypercalcemia in normal subjects and thyroparathyroidectomized patients. Miner Electrolyte Metab. 1985;11(6):369–373.

12. Kamycheva E, Jorde R, Haug E, Sager G, Sundsfjord J. Effects of acute hypercalcaemia on blood pressure in subjects with and without parathyroid hormone secretion. Acta Physiol Scand. 2005;184(2):113–119. doi: 10.1111/j.1365-201X.2005.01436.x

13. Marone C, Beretta-Piccoli C, Weidmann P. Acute hypercalcemic hypertension in man: role of hemodynamics, catecholamines, and renin. Kidney Int. 1981;20(1):92–96.

14. Tomaschitz A, Ritz E, Pieske B, Rus-Machan J, Kienreich K, Verheyen N et al. Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease. Metabolism. 2014;63(1):20–31. doi: 10.1016/j.metabol.2013.08.016

15. Brown JM, Vaidya A. Interactions between adrenalregulatory and calcium regulatory hormones in human health. Curr Opin Endocrinol Diabetes Obes. 2014;21(3):193–201. doi: 10.1097/MED.0000000000000062

16. Tomaschitz A, Pilz S, Rus-Machan J, Meinitzer A, Brandenburg VM, Scharnagl H et al. Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular mortality risk. Int J Cardiol. 2015;184:710–716. doi: 10.1016/j.ijcard.2015.03.062

17. Maniero C, Fassina A, Guzzardo V, Lenzini L, Amadori G, Pelizzo MR et al. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension. 2011;58(3):341–346. doi: 10.1161/HYPERTENSIONAHA.111.173948

18. Chau K, Holmes D, Melck A, Chan-Yan C. Secondary hypertension due to concomitant aldosterone-producing adenoma and parathyroid adenoma. Am J Hypertens. 2015;28(2):280–282. doi: 10.1093/ajh/hpu102

19. Kalla A, Krishnamoorthy P, Gopalakrishnan A, Garg J, Patel NC, Figueredo VM. Primary hyperparathyroidism predicts hypertension: Results from the National Inpatient Sample. Int J Cardiol. 2017;227:335–337. doi: 10.1016/j.ijcard.2016.11.080

20. Vaidya A, Brown JM, Williams JS. The renin-angiotensinaldosterone system and calcium-regulatory hormones. J Hum Hypertens. 2015;29(9):515–521. doi: 10.1038/jhh.2014.125

21. Laragh JH, Sealey JE. The plasma renin test reveals the contribution of body sodium-volume content (V) and reninangiotensin (R) vasoconstriction to longtermblood pressure. Am J Hypertens. 2011;24(11):1164–1180. doi: 10.1038/ajh.2011.171

22. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709–717. doi: 10.1056/NEJM199909023411001

23. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145–153. doi: 10.1056/NEJM200001203420301

24. Brown JM, Williams JS, Luther JM, Garg R, Garza AE, Pojoga LH et al. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone. Hypertension. 2014;63(2):273–280. doi: 10.1161/HYPERTENSIONAHA.113.01910

25. VaidyaA, Sun B, Larson C, Forman JP, Williams JS. Vitamin D3 therapy corrects the tissue sensitivity to angiotensin II akin to the action of a converting enzyme inhibitor in obese hypertensives: An Interventional Study. J Clin Endocrinol Metab. 2012;97(7): 2456–2465. doi: 10.1210/jc.2012-1156

26. Fischer E, Hannemann A, Rettig R, Lieb W, Nauck M, Pallauf A et al. A high aldosterone-to-renin ratio is associated with high serum parathyroid hormone concentrations in the general population. J Clin Endocrinol Metab. 2014;99(3):965–971. doi: 10.1210/jc.2013-3214

27. Brown J, de Boer IH, Robinson-Cohen C, Siscovick DS, Kestenbaum B, Allison M et al. Aldosterone, parathyroid hormone, and the use of renin-angiotensin-aldosterone system inhibitors: the multi-ethnic study of atherosclerosis. J Clin Endocrinol Metab. 2015;100(2):490–499. doi: 10.1210/jc.2014-3949

28. Tomaschitz A, Verheyen N, Meinitzer A, Pieske B, Belyavskiy E, Brussee H et al. Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: results from the EPATH randomized, placebo-controlled trial. J Hypertens. 2016;34 (7):1347–1356. doi: 10.1097/HJH.0000000000000927

29. Zaheer S, Brown JM, Connors M, Williams JS, Adler GK, Vaidya A. Angiotensin-converting enzyme inhibition and parathyroid hormone secretion. Int J Endocrinol. 2017;2017:4138783. doi: 10.1155/2017/4138783

30. Tomaschitz A, Pilz S. Interplay between sodium and calcium regulatory hormones: a clinically relevant research field. Hypertension. 2014;63(2):212–214. doi: 10.1161/HYPERTENSIONAHA.113.02253

31. Isales CM, Barrett PQ, Brines M, Bollag W, Rasmussen H. Parathyroid hormone modulates angiotensin II-induced aldosterone secretion from the adrenal glomerulosa cell. Endocrinology. 1991;129(1):489–495. doi: 10.1210/endo-129-1-489

32. Mazzocchi G, Aragona F, Malendowicz LK, Nussdorfer GG. PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells. Am J Physiol Endocrinol Metab. 2001;280(2): E209–E213. doi: 10.1152/ajpendo.2001.280.2.E209

33. Saussine C, Judes C, Massfelder T, Musso MJ, Simeoni U, Hannedouche T et al. Stimulatory action of parathyroid hormone on renin secretion in vitro: a study using isolated rat kidney, isolated rabbit glomeruli and superfused dispersed rat juxtaglomerular cells. Clin Sci. 1993;84(1):11–19.

34. Helwig JJ, Musso MJ, Judes C, Nickols GA. Parathyroid hormone and calcium: interactions in the control of renin secretion in the isolated, nonfiltering rat kidney. Endocrinology. 1991;129(3): 1233–1242. doi: 10.1210/endo-129-3-1233

35. Bernini G, Moretti A, Lonzi S, Bendinelli C, Miccoli P, Salvetti A. Renin-angiotensin-aldosterone system in primary hyperparathyroidism before and after surgery. Metabolism. 1999;48 (3):298–300.

36. Kovács L, Góth MI, Szabolcs I, Dohán O, Ferencz A, Szilágyi G. The effect of surgical treatment on secondary hyperaldosteronism and relative hyperinsulinemia in primary hyperparathyroidism. Eur J Endocrinol. 1998;138(5):543–547.

37. Pacifici R, Perry HM, Shieber W, Biglieri E, Droke DM, Avioli LV. Adrenal responses to subtotal parathyroidectomy for primary hyperparathyroidism. Calcif Tissue Int. 1987;41(3):119–123.

38. Brunaud L, Germain A, Zarnegar R, Rancier M, Alrasheedi S, Caillard C et al. Serum aldosterone is correlated positively to parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism. Surgery. 2009;146(6):1035–1041. doi: 10.1016/j.surg.2009.09.041

39. Tomaschitz A, Pilz S, Ritz E, Grammer T, Drechsler C, Boehm BO et al. Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin Chim Acta. 2010;411(17–18):1354–1360. doi: 10.1016/j.cca.2010.05.037

40. Pilz S, März W, Wellnitz B, Seelhorst U, FahrleitnerPammer A, Dimai HP et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab. 2008;93(10):3927–3935. doi: 10.1210/jc.2008-0784

41. Carrara D, Bernini M, Bacca A, Rugani I, Duranti E, Virdis A et al. Cholecalciferol administration blunts the systemic reninangiotensin system in essential hypertensives with hypovitaminosis D. J Renin Angiotensin Aldosterone Syst. 2014;15(1):82–87. doi: 10.1177/1470320312471149

42. Scragg R, Slow S, Stewart AW, Jennings LC, Chambers ST, Priest PC et al. Long-term high-dose vitamin D3 supplementation and blood pressure in healthy adults: a randomized controlled trial. Hypertension. 2014;64(4):725–730. doi: 10.1161/HYPERTENSIONAHA.114.03466