References

arthyper

Артериальная гипертензия

"Arterial’naya Gipertenziya" ("Arterial Hypertension")

1607-419X2411-8524

Antihypertensive League

10.18705/1607-419X-2017-23-4-282-293

arthyper-659

Research Article

ОБЗОР

REVIEW

СЕРДЕЧНО-СОСУДИСТАЯ ПАТОЛОГИЯ ПРИ БЕССИМПТОМНОМ ПЕРВИЧНОМ ГИПЕРПАРАТИРЕОЗЕ

ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM AND CARDIOVASCULAR PATHOLOGY

Рунова

Г. Е.

Runova

G. E.

Рунова Гюзель Евгеньевна — кандидат медицинских наук, ассистент кафедры эндокринологии лечебного факультета ФГБОУ ВО Первый МГМУ им. И. М. Сеченова Минздрава России.

ул. Погодинская, д. 1, Москва, Россия, 119435.

Gyuzel E. Runova, MD, PhD, Endocrinologist, Medical Faculty, I. M. Sechenov First Moscow State Medical University.

1 Pogoninskaya street, Moscow, 119435.

guzelvolkova@yandex.ru

Фадеев

В. В.

Fadeev

V. V.

Фадеев Валентин Викторович — доктор медицинских наук, профессор, член-корреспондент Российской академии наук, заведующий кафедрой эндокринологии, директор клиники эндокринологии ФГБОУ ВО Первый МГМУ им. И. М. Сеченова Минздрава России.

Москва.

Valentin V. Fadeev, MD, PhD, Professor, Corresponding Member of the Russian Academy of Science, Head, Endocrinology Department, I. M. Sechenov First Moscow State Medical University.

Федеральное государственное бюджетное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И. М. Сеченова» Министерства здравоохранения Российской Федерации.РоссияI. M. Sechenov First Moscow State Medical University.Russian Federation

2017

28092017

234282293

2017

Рунова Г.Е., Фадеев В.В.

Runova G.E., Fadeev V.V.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://htn.almazovcentre.ru/jour/article/view/659

Паратиреоидный гормон (ПТГ), помимо непосредственной регуляции фосфорно-кальциевого обмена, оказывает влияние на сердечно-сосудистую систему. Рецепторы ПТГ обнаружены в миокарде, гладкомышечных клетках сосудов и клубочковой зоны коры надпочечников. Высокая смертность среди больных с манифестным первичным гиперпаратиреозом (ПГПТ) обусловлена прежде всего сердечно-сосудистыми заболеваниями. В большинстве работ, посвященных проблеме бессимптомного ПГПТ, также затрагиваются вопросы патологии сердечно-сосудистой системы, обусловленные непосредственными эффектами ПТГ. Чаще всего встречаются артериальная гипертензия, гипертрофия миокарда левого желудочка и диастолическая дисфункция, патология комплекса интима-медиа, повышение жесткости сосудов и эндотелиальная дисфункция, также упоминаются кальцинаты и нарушения проводимости. Тем не менее остается нерешенным вопрос причинно-следственных связей, клинической значимости вышеописанных изменений, их влияния на сердечно-сосудистую и общую смертность при бессимптомном ПГПТ, а также их обратимость и снижение смертности после хирургического лечения по поводу бессимптомного ПГПТ. В условиях преобладания бессимптомных форм ПГПТ (часто без абсолютных показаний к хирургическому лечению) представляется особенно актуальной клиническая значимость сердечно-сосудистых осложнений, их влияния на сердечно-сосудистую и общую смертность, а также их обратимость на фоне хирургического лечения.

Parathyroid hormone (PTH) controls regulation of phosphorus-calcium metabolism and affects the cardiovascular system. PTH receptors have been found in the myocardium, smooth muscle cells of the vessels and the glomerular zone of the adrenal cortex. Cardiovascular diseases are the most common cause of high mortality among patients with primary hyperparathyroidism (PHPT). Moreover, asymptomatic patients also demonstrate cardiovascular involvement due to the direct effects of PTH. The most common are arterial hypertension, left ventricular myocardial hypertrophy and diastolic dysfunction, as well as intima-media complex pathology, vascular stiffness and endothelial dysfunction, calcifications and conduction disorders. Nevertheless, the causeeffect relationship and the impact on cardiovascular and overall mortality in asymptomatic PHPT are unknown. The reversibility of the abnormal changes and reduction in mortality after surgical treatment in asymptomatic PHPT are not well investigated. Regarding the high prevalence of asymptomatic PHPT (often without absolute indications for surgical treatment), cardiovascular complications, their impact on cardiovascular and general mortality, and reversibility after surgical treatment are highly important.

первичный гиперпаратиреозпатология околощитовидных железсердечнососудистые заболеваниярецепторы паратиреоидного гормонапоражение органов-мишеней

Primary hyperparathyroidismparathyroid pathologycardiovascular diseasesparathyroid hormone receptorstarget organ damage

References1

Вороненко И. В., Сыркин А. Л., Рожинская Л. Я., Мельниченко Г. А. Гиперпаратиреоз и патология сердечно-сосудистой системы. Остеопороз и остеопатии. 2006;2:33–41. [Voronenko IV, Syrkin AL, Rozhinskaya LYa, Melnichenko GA. Hyperparathyreosis and cardiovascular pathology. Ostheoporosis and Ostheopathy. 2006;2:33–41. In Russian].

Bollerslev J, Marcocci C, Sosa M, Nordenström J, Bouillon R, Mosekilde L. Current evidence for recommendation of surgery, medical treatment and vitamin D repletion in mild primary hyperparathyroidism. Eur J Endocrinol. 2011;165(6):851–64. doi:10.1530/EJE-11–0589

Castellano E, Tassone F, Attanasio R, Gianotti L, Pellegrino M, Borretta G. Mild primary hyperparathyroidism as defined in the Italian Society of Endocrinology’s Consensus Statement: prevalence and clinical features. J Endocrinol Invest. 2016;39 (3):349–54.

Marcocci C, Brandi ML, Scillitani A, Corbetta S, Faggiano A, Gianotti L et al. Italian Society of Endocrinology Consensus Statement: definition, evaluation and management of patients with mild primary hyperparathyroidism. J Endocrinol Invest. 2015;38 (5):577–93. doi:10.1007/s40618–015–0261–3

Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561–9. doi:10.1210/jc.2014–1413

Schlüter K-D. PTH and PTHrP: Similar structures but different functions. News Physiol Sci. 1999;14:243–249.

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):489–95.

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): E209–13.

Anderson P, Rydberg E, Willenheimer R. Primary hyperparathyroidism and heаrt disease — a review. Europ Heart J. 2004;25(20):1776–1787.

Cansu GB, Yılmaz N, Özdem S, Balcı MK, Süleymanlar G, Arıcı C et al. Parathyroidectomy in asymptomatic primary hyperparathyroidism reduces carotid intima-media thickness and arterial stiffness. Clin Endocrinol (Oxf). 2016;84(1):39–47.

Schillaci G, Pucci G, Pirro M, Monacelli M, Scarponi AM, Manfredelli MR et al. Large-artery stiffness: a reversible marker of cardiovascular risk in primary hyperparathyroidism. Atherosclerosis. 2011;218(1):96–101.

Tordjman KM, Yaron M, Izkhakov E, Osher E, Shenkerman G, Marcus-Perlman Y et al. Cardiovascular risk factors and arterial rigidity are similar in asymptomatic normocalcemic and hypercalcemic primary hyperparathyroidism. Eur J Endocrinol. 2010;162(5):925–33.

Walker MD, Fleischer J, Rundek T, McMahon DJ, Homma S, Sacco R et al. Silverberg. Carotid vascular abnormalities in primary hyperparathyroidism. J Clin Endocrinol Metab. 2009;94 (10):3849–56.

Smith JC, Page MD, John R, Wheeler MH, Cockcroft JR, Scanlon MF et al. Augmentation of central arterial pressure in mild primary hyperparathyroidism. J Clin Endocrinol Metab. 2000;85 (10):3515–9.

Sangal AK, Kevwitch M, Rao DS, Rival J. Hypomagnesemia and hypertension in primary hyperparathyroidism. South Med J. 1989;82(9):1116–8.

Marone C, Beretta-Piccoli C, Weidmann P. Role of haemodynamics, catecholamines and renin in acute hypercalcaemic hypertension in man. Clin Sci (Lond). 1980;59 (Suppl 6): 369s-71s.

Schiffl H, Lang SM. Hypertension Secondary to PHPT: Cause or Coincidence? Int J Endocrinol. 2011;2011:974647. doi:10.1155/2011/974647

Gennari C, Nami R, Gonnelli S. Hypertension and primary hyperparathyroidism: the role of adrenergic and reninangiotensin-aldosterone systems. Miner Electrolyte Metab. 1995;21(1–3):77–81.

Vlachakis ND, Frederics R, Velasquez M, Alexander N, Singer F, Maronde RF. Sympathetic system function and vascular reactivity in hypercalcemic patients. Hypertension. 1982;4(3):452–458.

Kosch M, Hausberg M, Vormbrock K, Kisters K, Gabriels G, Rahn KH et al. Impaired flow mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy. Cardiovasc Res. 2000;47(4):813–818.

Erne P, Bolli P, Burgisser E, Buhler FR. Correlation of platelet calcium with blood pressure. Effect of antihypertensive therapy. N England J Med. 1984;310(17):1084–1088.

Poch E, Fernandez-Llama P, Botey A, Gaya J, Darnell A, Rivera F et al. Parathyroid hormone and platelet cytosolic calcium concentration in essential hypertension. Nephrol Dial Transplant. 1995;10(3):366–371.

Schiffl H, Fricke H, Sitter T. Hypertension secondary to early-stage kidney disease: the pathogenetic role of altered cytosolic calcium (Ca) homeostasis of vascular smooth muscle cells. Аm J Kidney Dis. 1993;21(2):51–57.

Camilletti A, Moretti N, Giacchetti G, Faloia E, Martarelli D, Mantero F et al. Decreased nitric oxide levels and increased calcium content in platelets of hypertensive patients. Am J Hypertens. 2001;14(4–1):382–386.

Fardella C, Rodriguez-Portales JA. Intracellular calcium and blood pressure: comparison between primaryhyperparathyroidism and essential hypertension. J Endocr Invest 1995;18(11):827– 832.

Dominiczak AF, Lyall F, Morton JJ, Dargie HJ, Boyle IT, Tune TT et al. Blood pressure, left ventricular mass and intracellular calcium in primary hyperparathyroidism. Clinical Science. 1990;78 (2):127–132.

Vaidya A, Curhan GC, Paik JM, Kronenberg H, Taylor EN. Hypertension, antihypertensive medications, and risk of incident primary hyperparathyroidism. J Clin Endocrinol Metab. 2015;100 (6):2396–2404.

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

Hulter HN, Melby JC, Peterson JC, Cooke CR. Chronic continuous PTH infusion results in hypertension in normal subjects. J Clin Hypertens. 1986;2(4):360–70.

Grant FD, Mandel SJ, Brown EM, Williams GH, Seely EW. Interrelationships between the renin-angiotensin-aldosterone and calcium homeostatic systems. J Clin Endocrinol Metab. 1992;75 (4):988–92.

Verheyen N, Fahrleitner-Pammer A, Pieske B, Meinitzer A, Belyavskiy E, Wetzel J et al. Parathyroid hormone, aldosteroneto-renin ratio and fibroblast growth factor-23 as determinants of nocturnal blood pressure in primary hyperparathyroidism: the eplerenone in primary hyperparathyroidism trial. J Hypertens. 2016. 34(9):1778–86. doi:10.1097/HJH.0000000000001004

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 (Lond). 1993;84(1):11–9.

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):1233–42.

Fallo F, Rocco S, Pagotto U, Zangari M, Luisetto G, Mantero F. Aldosterone and pressor responses to angiotensin II in primary hyperparathyroidism. J Hypertens Suppl. 1989;7(6): S192–3.

Maniero C, Fassina A, Guzzardo V, Lenzini L, Amadori G, Pelizzo MR et al. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension. 2011;58(3):341–6.

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):280–2. doi:10.1093/ ajh/hpu102

Barkan A, Marilus R, Winkelsberg G, Yeshurun D, Blum I. Primary hyperparathyroidism: possible cause of primary hyperaldosteronism in a 60-year-old woman. J Clin Endocrinol Metab. 1980;51(1):144–7.

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.

Tomaschitz A, Verheyen N, Meinotzer 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

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

Neunteufl T, Heher S, Prager G, Katzenschlager R, Abela C, Niederle B et al. Effects of successful parathyroidectomy on altered arterial reactivity in patients with hypercalcaemia: results of a 3-year follow-up study. Clinic Endocrin. 2000;53(2):229–233.

Lewanczuk RZ, Resnick LM, Ho MS, Benishin CG, Shan J. Pang PKT. Clinical aspects of parathyroid hypertensive factor. J Hypertens Suppl. 1994;12(1):11–16.

Batra J, Buttar RS, Kaur P, Kreimerman J, Melamed ML. FGF-23 and cardiovascular disease: review of literature. Curr Opin Endocrinol Diabetes Obes. 2016;23(6):423–429.

Han X, Quarles LD. Multiple faces of fibroblast growth factor-23. Curr Opin Nephrol Hypertens. 2016;25(4):333–42.

AACE/AAES position statement on the diagnosis and management of primary hyperparathyroidism. Endocr Pract. 2005;11(1):49–54. doi:10.4158/EP.11.1.49

Heyliger A, Tangpricha V, Weber C, Sharma J. Para- thyroidectomy decreases systolic and diastolic blood pressure in hypertensive patients with primary hyperparathyroidism. Surgery. 2009;146(6):1042–1047. PMCID: 2845911.

Nainby-Luxmoore JC, Langford HG, Nelson NC, Watson RL, Barnes TY. A case-comparison study of hypertension and hyperparathyroidism. J Clin Endocrinol Metab. 1982;55 (2):303–6.

Bollerslev J, Rosen T, Mollerup CL, Nordenström J, Baranowski M, Franco C et al. Effect of surgery on cardiovascular risk factors in mild primary hyperparathyroidism. J Clin Endocrinol Metab. 2009;94(7):2255–2261.

Dalberg K, Brodin LA, Juhlin-Dannfelt A, Farnebo LO. Cardiac function in primary hyperparathyroidism before and after operation. An echocardiographic study. Eur J Surg. 1996;162 (3):171–6.

McMahon D, Carrelli A, Palmeri N, Zhang C, DiTullio M, Silverberg SJ et al. Effect of parathyroidectomy on LV mass. J Clin Endocrinol Metab. 2015;100(12):4399–4407.

Piovesan A, Molineri N, Casasso F, Emmolo I, Ugliengo G, Cesario F et al. Left ventricular hypertrophy in primary hyperparathyroidism. Effects of successful parathyroidectomy. Clin Endocrinol. 1999;50(3):321–328.

Pierdomenico SD, Cuccurullo F. Risk reduction after regression of echocardiographic left ventricular hypertrophy in hypertension: a meta-analysis. Am J Hypertens. 2010;23(8):876–881.

Hedback G, Tisell LE, Bengtsson BA, Hedman I, Oden A. Premature death in patients operated on for PHPT. World J Surg. 1990;14(6):829–835.

Ljunghall S, Jakobsson S, Joborn C, Palmer M, Rastad J, Akerstrom G. Longitudinal studies of mild PHPT. J Bone Miner Res. 1991;6(Suppl 2):11–16.

Hedback G, Oden A. Increased risk of death from PHPT — an update. Eur J Clin Invest. 1998;28(4):271–276.

Wermers RA, Khosla S, Atkinson EJ, Grant CS, Hodgson SF, O’Fallon WM et al. Survival after the diagnosis of hyperparathyroidism: a population-based study. Am J Med. 1998;104(2):115–122.

Nilsson IL, Yin L, Lundgren E, Rastad J, Ekbom A. Clinical presentation of primary cohort analysis on mortality from nonmalignant causes. J Bone Miner Res. 2002;17(2):68–74.

Vestergaard P, Mollerup CL, Frokjaer VG, Christiansen P, Blichert-Toft M, Mosekilde L. Cardiovascular events before and after surgery for primary hyperparathyroidism. World J Surg. 2003; 27(2):216–222.

Yu N, Donnan PT, Flynn RW, Murphy MJ, Smith D, Rudman A et al. Increased mortality and morbidity in mild primary hyperparathyroid patients. The Parathyroid Epidemiology and Audit Research Study (PEARS). Clin Endocrinol. 2010;73(1):30–34.

Yu N, Leese GP, Donnan PT What predicts adverse outcomes in untreated primary hyperparathyroidism? The Parathyroid Epidemiology and Audit Research Study (PEARS). Clin Endocrinol. 2013;79(1):27–34.

Anderson JL, Vanwoerkom RC, Horne BD, Bair TL, May HT, Lappé DL et al. Parathyroid hormone, vitamin D, renal dysfunction, and cardiovascular disease: dependent or independent risk factors? Am Heart J. 2011;162(2):331–339.

Hagstrom E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundström J et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009;119 (21):2765–2771.

Lumachi F, Ermani M, Luisetto G, Nardi A, Basso SM, Camozzi V. Relationship between serum parathyroid hormone, serum calcium and arterial blood pressure in patients with primary hyperparathyroidism: results of a multivariate analysis. Eur J Endocrinol 2002;146(5):643–647.

Uden P, Chan A, Duh QY, Siperstein A, Clark OH. Primary hyperparathyroidism in younger and older patients: symptoms and outcome of surgery. World J Surg. 1992;16(4):791–7; discussion 798.

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

Walker MD, Fleischer J, Rundek T, McMahon DJ, Homma S, Sacco R et al. Carotid vascular abnormalities in primary hyperparathyroidism. J Clin Endocrinol Metab. 2009;94 (10):3849–56.

Nilsson IL, Rastad J, Johansson K, Lind L. Endothelial vasodilatory function and blood pressure response to local and systemic hypercalcemia. Surgery. 2001;130(6):986–90.

Andrukhova O, Slavic S, Smorodchenko A, Zeitz U, Shalhoub V, Lanske B et al. FGF23 regulates renal sodium handling and blood pressure. EMBO Mol Med. 2014;6(6):744–759.

Yu N, Donnan PT, Murphy MJ, Leese P. Epidemiology of primary hyperparathyroidism in tayside, Scotland, UK. Clin Endocrinol (Oxf). 2009;71(4):485–493.

Wermers R, Khosla S, Atkinson EJ, Achenbach SJ, Oberg AL, Grant CS et al. Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993–2001: an update on the changing epidemiology of the disease. J Bone Miner Res. 2006;21(1): 171–7.

Chiavistelli S, Bilezikian J. Does calcium intake influence the development of primary hyperparathyroidism? IBMS BoneKEy. 2013;10:314.

Yeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab. 2013;98(3):1122–1129. doi:10.1210/jc.2012–4022

De Lucia F, Minisola S, Romagnoli E, Pepe J, Cipriani C, Scillitani A et al. Effect of gender and geographic location on the expression of primary hyperparathyroidism. J Endocrinol Invest. 2013;36(2):123–126.

Eufrazino C, Veras A, Bandeira F. Epidemiology of primary hyperparathyroidism and its non-classical manifestations in the city of Recife, Brazil. Clin Med Insights Endocrinol Diabetes. 2013;6:69–74. doi:10.4137/CMED.S13147

The authors declare that there are no conflicts of interest present.