Динамика параметров ренин-ангиотензин-альдостероновой системы после хирургического лечения первичного гиперпаратиреоза
DOI: 10.26442/00403660.2020.10.000725
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Dobreva E.A., Bibik E.E., Eremkina A.K., et al. Dynamic changes of renin-angiotensin-aldosterone system parameters after surgery of primary hyperparathyroidism. Therapeutic Archive. 2020; 92 (10): 63–69. DOI: 10.26442/00403660.2020.10.000725
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Материалы и методы. Проведено сравнительное исследование пациентов с ПГПТ и группы контроля. Первый этап включал обследование 56 пациентов (группа 1) до и на 3-и сутки после ПТЭ. Второй этап исследования проводился через 12 мес после ПТЭ у 27 пациентов с ремиссией ПГПТ (группа 2). Пациентам и здоровым добровольцам в сыворотке определялись основные показатели фосфорно-кальциевого обмена и параметры РААС (активность ренина плазмы – АРП, альдостерон и ангиотензин II – АТ II).
Результаты. У пациентов продемонстрированы изменения активности РААС (снижение АРП, повышение АТ II) в активной стадии ПГПТ относительно здорового контроля, достигавшие статистической значимости в группе 1 (р<0,001 для обоих параметров). Отличий показателей альдостерона не обнаружено (p1=0,090; p2=0,140). На 3-и сутки после ПТЭ (группа 1) выявлены снижение альдостерона (p=0,009) и тенденция к снижению АРП (p=0,030). Однако через 12 мес после ПТЭ на фоне стойкой нормализации кальция и паратгормона прослеживаются повышение АРП (р=0,018), снижение АТ II (р=0,032) относительно исходных значений и их нормализация. Оценка корреляций параметров фосфорно-кальциевого обмена и РААС продемонстрировала противоречивые результаты. Достоверного влияния ингибиторов ангиотензинпревращающего фермента и блокаторов рецепторов АТ II на показатели фосфорно-кальциевого обмена у пациентов с ПГПТ не отмечено.
Заключение. У пациентов с ПГПТ однозначной корреляции параметров фосфорно-кальциевого обмена и РААС не выявлено, однако отмечено повышение концентрации АТ II, вероятно, способствующего развитию артериальной гипертензии при данной эндокринопатии. Радикальная ПТЭ может оказывать положительное влияние на уровень АТ II.
Ключевые слова: первичный гиперпаратиреоз, ренин-ангиотензин-альдостероновая система, паратгормон, альдостерон, ангиотензин II, артериальная гипертензия.
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Aim. To study an activity of the Renin-Angiotensin-Aldosterone System (RAAS) components in patients with primary hyperparathyroidism (PHPT) before and after parathyroidectomy (PTE).
Materials and methods. A comparative study of patients with PHPT and control group. The first stage of the study included 56 patients with PHPT (group 1) before and on the third day after PTE. The second stage was carried out in 27 patients with remission of PHPT (group 2). All patients and healthy volunteers were tested for the main parameters of phosphorus-calcium metabolism and the RAAS parameters (plasma renin activity – PRA, serum aldosterone, angiotensin II – AT II).
Results. Patients with active PHPT demonstrated changes in RAAS activity (lower PRA, higher AT II level) comparing to control group, that have statistical significance in group 1 (p<0.001 for both parameters). There were no significant differences in aldosterone levels (p1=0.090; p2=0.140). On the third day after PTE (group 1), a decrease in aldosterone level (p=0.009) and a tendency to decrease in PRA (p=0.030) were detected. However, an increase in PRA (p=0.018), a decrease in AT II concentration (p=0.032) comparing to the initial values and their normalization were observed 12 months after surgery when permanent normal serum calcium and PTH levels had been achieved. There were controversial correlations between the parameters of phosphorus-calcium metabolism and RAAS. The influence of angiotensin-converting-enzyme inhibitors and AT II receptor blockers on phosphorus-calcium metabolism in patients with PHPT was not observed.
Conclusion. In patients with PHPT, there were no сlear correlations of phosphorus-calcium metabolism parameters with RAAS, however an increase of AT II concentration was noted, that can take part in a development of hypertension for this endocrinopathy. PTE can have a positive effect on AT II level.
Keywords: primary hyperparathyroidism, renin-angiotensin-aldosterone system, parathyroid hormone, aldosterone, angiotensin II, hypertension.
2. Kalla A, Krishnamoorthy P, Gopalakrishnan A, et al. Primary hyperparathyroidism predicts hypertension: Results from the National Inpatient Sample. Int J Cardiol. 2017;227:335-7. doi: 10.1016/j.ijcard.2016.11.080
3. Pepe J, Cipriani C, Sonato C, et al. Cardiovascular manifestations of primary hyperparathyroidism: a narrative review. Eur J Endocrinol. 2017;177(6):R297-R308. doi: 10.1530/EJE-17-0485
4. Wetzel J, Pilz S, Grübler MR, et al. Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: The EPATH trial. J Clin Hypertens (Greenwich). 2017;19(11):1173-80. doi: 10.1111/jch.13064
5. Pal R, Mukherjee S, Bhadada SK, et al. Persistence of “non-dipping” pattern in blood pressure after curative parathyroidectomy in apparently normotensive patients with symptomatic primary hyperparathyroidism. Minerva Endocrinol. 2020;45(3):181-8. doi: 10.23736/S0391-1977.19.03104-3
6. Nelson JA, Alsayed M, Milas M. The role of parathyroidectomy
in treating hypertension and other cardiac manifestations of primary hyperparathyroidism. Gland Surg. 2020;9(1):136-41. doi: 10.21037/gs.2019.12.12
7. Hassan M, Qureshi W, Sroujieh LS, et al. Interplay of parathyroid hormone and aldosterone antagonist in prevention of heart failure hospitalizations in chronic kidney disease. J Renin Angiotensin Aldosterone Syst: JRAAS. 2014;15(3):278-85. doi: 10.1177/1470320314539180
8. Gambardella J, De Rosa M, Sorriento D, et al. Parathyroid Hormone Causes Endothelial Dysfunction by Inducing Mitochondrial ROS and Specific Oxidative Signal Transduction Modifications. Oxid Med Cell Longev. 2018;2018:9582319. doi: 10.1155/2018/9582319
9. Fisher SB, Perrier ND. Primary hyperparathyroidism and hypertension. Gland Surg. 2020;9(1):142-9. doi: 10.21037/gs.2019.10.21
10. Tomaschitz A, Pilz S, Rus-Machan J, et al. Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular mortality risk. Int J Cardiol. 2015;184:710-6. doi: 10.1016/j.ijcard.2015.03.062
11. Brown JM, Vaidya A. Interactions between adrenal-regulatory and
calcium-regulatory hormones in human health. Curr Opin
Endocrinol Diabetes Obes. 2014;21(3):193-201. doi: 10.1097/
MED.0000000000000062
12. Isales CM, Barrett PQ, Brines M, et al. Parathyroid hormone modulates angiotensin II-induced aldosterone secretion from the adrenal glomerulosa cell. Endocrinology. 1991;129(1):489-95. doi: 10.1210/endo-129-1-489
13. Mazzocchi G, Aragona F, Malendowicz LK, Nussdorfer GG. PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells. Am J Physiol Endocrinol Metabol. 2001;280(2):E209-13. doi: 10.1152/ajpendo.2001.280.2.E209
14. Olgaard K, Lewin E, Bro S, et al. Enhancement of the stimulatory effect of calcium on aldosterone secretion by parathyroid hormone. Miner Electrolyte Metab. 1994;20(5):309-14.
15. Rosenberg J, Pines M, Hurwitz S. Response of adrenal cells to parathyroid hormone stimulation. J Endocrinol. 1987;112(3):431-37. doi: 10.1677/joe.0.1120431
16. Saussine C, Judes C, Massfelder 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. doi: 10.1042/cs0840011
17. 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. doi: 10.1210/endo-129-3-1233
18. Maniero C, Fassina A, Guzzardo V, et al. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension. 2011;58(3):341-6. doi: 10.1161/HYPERTENSIONAHA.111.173948
19. Lenzini L, Prisco S, Vanderriele PE, et al. PTH Modulation by Aldosterone and Angiotensin II is Blunted in Hyperaldosteronism and Rescued by Adrenalectomy. J Clin Endocrinol Metab. 2019;104(9):3726-34. doi: 10.1210/jc.2019-00143
20. Brown J, de Boer IH, Robinson-Cohen C, 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):490-9. doi: 10.1210/jc.2014-3949
21. Fischer E, Hannemann A, Rettig R, 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):965-71. doi: 10.1210/jc.2013-3214
22. Tomaschitz A, Verheyen N, Meinitzer A, 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):1347-56. doi: 10.1097/
HJH.0000000000000927
23. Zaheer S, Brown JM, Connors M, et al. Angiotensin-Converting Enzyme Inhibition and Parathyroid Hormone Secretion. Int J Endocrinol. 2017;2017:4138783. doi: 10.1155/2017/4138783
24. Asbach E, Bekeran M, König A, et al. Primary and Secondary Hyperparathyroidism in Patients with Primary Aldosteronism – Findings From the German Conn’s Registry. Exp Clin Endocrinol Diabetes. 2020;128(4):246-54. doi: 10.1055/a-1027-6472
25. Zhou D, Liu M, Yan Z. Primary aldosteronism complicated by hyperparathyroidism: report of one case and literature review. Int J Clin Exp Pathol. 2019;12(8):3096-101.
26. Concistré A, Petramala L, Zinnamosca L, et al. Primary aldosteronism with concurrent primary hyperparathyroidism: clinical case load in a single centre. Eur Rev Med Pharmacol Sci. 2015;19(6):971-76. https://www.europeanreview.org/article/8681
27. Vaidya A, Brown JM, Williams JS. The renin-angiotensin-aldosterone system and calcium-regulatory hormones. J Hum Hypertens. 2015;29(9):515-21. doi: 10.1038/jhh.2014.125
28. Beysel S, Caliskan M, Kizilgul M, et al. Parathyroidectomy improves cardiovascular risk factors in normocalcemic and hypercalcemic primary hyperparathyroidism. BMC Cardiovasc Disord. 2019;19(1):106. doi: 10.1186/s12872-019-1093-4
29. Bernini G, Moretti A, Lonzi S, et al. Renin-angiotensin-aldosterone system in primary hyperparathyroidism before and after surgery. Metabolism. 1999;48(3):298-300. doi: 10.1016/s0026-0495(99)90075-6
30. Kovacs L, Goth MI, Szabolcs I, et al. The effect of surgical treatment on secondary hyperaldosteronism and relative hyperinsulinemia in primary hyperparathyroidism. Eur J Endocrinol. 1998;138(5):543-47. doi: 10.1530/eje.0.1380543
31. Pacifici R, Perry HM 3rd, Shieber W, et al. Adrenal responses to subtotal parathyroidectomy for primary hyperparathyroidism. Calcif Tissue Int. 1987;41(3):119-23. doi: 10.1007/bf02563790
32. Brunaud L, Germain A, Zarnegar R, et al. Serum aldosterone is correlated positively to parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism. Surgery. 2009;146(6):1035-41. doi: 10.1016/j.surg.2009.09.041
33. Добрева Е.А., Бибик Е.Е., Еремкина А.К. и др. Взаимосвязь показателей кальциевого обмена и ренин-ангиотензин-альдостероновой системы при первичном гиперпаратиреозе в до- и раннем послеоперационном периодах. Артериальная гипертензия. 2019;25(6):630-8 [Dobreva EA, Bibik EE, Eremkina AK, et al. Correlations between parameters of calcium metabolism and renin-angiotensin-aldosterone system in patients with primary hyperparathyroidism in the pre- and early postoperative periods. Arterial Hypertension. 2019;25(6):630-8 (In Russ.)]. doi: 10.18705/1607-419X-2019-25-6-630-638
34. Brown JM, Williams JS, Luther JM, et al. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone. Hypertension. 2014;63(2):273-80. doi: 10.1161/HYPERTENSIONAHA.113.01910
35. DeLuccia R, Cheung M, Ramadoss R, et al. The Endocrine Role of Bone in Cardiometabolic Health. Cur Nutr Rep. 2019;8(3):281-94. doi: 10.1007/s13668-019-00286-0
36. Sorriento D, De Luca N, Trimarco B, Iaccarino G. The Antioxidant Therapy: New Insights in the Treatment of Hypertension. Front Physiol. 2018;9:258. doi: 10.3389/fphys.2018.00258
37. Grubler MR, Marz W, Pilz S, et al. Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence. Rev Endocr Metabc Disord. 2017;18(2):259-72. doi: 10.1007/s11154-017
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1. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. doi: 10.1093/eurheartj/ehy339
2. Kalla A, Krishnamoorthy P, Gopalakrishnan A, et al. Primary hyperparathyroidism predicts hypertension: Results from the National Inpatient Sample. Int J Cardiol. 2017;227:335-7. doi: 10.1016/j.ijcard.2016.11.080
3. Pepe J, Cipriani C, Sonato C, et al. Cardiovascular manifestations of primary hyperparathyroidism: a narrative review. Eur J Endocrinol. 2017;177(6):R297-R308. doi: 10.1530/EJE-17-0485
4. Wetzel J, Pilz S, Grübler MR, et al. Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: The EPATH trial. J Clin Hypertens (Greenwich). 2017;19(11):1173-80. doi: 10.1111/jch.13064
5. Pal R, Mukherjee S, Bhadada SK, et al. Persistence of “non-dipping” pattern in blood pressure after curative parathyroidectomy in apparently normotensive patients with symptomatic primary hyperparathyroidism. Minerva Endocrinol. 2020;45(3):181-8. doi: 10.23736/S0391-1977.19.03104-3
6. Nelson JA, Alsayed M, Milas M. The role of parathyroidectomy
in treating hypertension and other cardiac manifestations of primary hyperparathyroidism. Gland Surg. 2020;9(1):136-41. doi: 10.21037/gs.2019.12.12
7. Hassan M, Qureshi W, Sroujieh LS, et al. Interplay of parathyroid hormone and aldosterone antagonist in prevention of heart failure hospitalizations in chronic kidney disease. J Renin Angiotensin Aldosterone Syst: JRAAS. 2014;15(3):278-85. doi: 10.1177/1470320314539180
8. Gambardella J, De Rosa M, Sorriento D, et al. Parathyroid Hormone Causes Endothelial Dysfunction by Inducing Mitochondrial ROS and Specific Oxidative Signal Transduction Modifications. Oxid Med Cell Longev. 2018;2018:9582319. doi: 10.1155/2018/9582319
9. Fisher SB, Perrier ND. Primary hyperparathyroidism and hypertension. Gland Surg. 2020;9(1):142-9. doi: 10.21037/gs.2019.10.21
10. Tomaschitz A, Pilz S, Rus-Machan J, et al. Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular mortality risk. Int J Cardiol. 2015;184:710-6. doi: 10.1016/j.ijcard.2015.03.062
11. Brown JM, Vaidya A. Interactions between adrenal-regulatory and
calcium-regulatory hormones in human health. Curr Opin
Endocrinol Diabetes Obes. 2014;21(3):193-201. doi: 10.1097/
MED.0000000000000062
12. Isales CM, Barrett PQ, Brines M, et al. Parathyroid hormone modulates angiotensin II-induced aldosterone secretion from the adrenal glomerulosa cell. Endocrinology. 1991;129(1):489-95. doi: 10.1210/endo-129-1-489
13. Mazzocchi G, Aragona F, Malendowicz LK, Nussdorfer GG. PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells. Am J Physiol Endocrinol Metabol. 2001;280(2):E209-13. doi: 10.1152/ajpendo.2001.280.2.E209
14. Olgaard K, Lewin E, Bro S, et al. Enhancement of the stimulatory effect of calcium on aldosterone secretion by parathyroid hormone. Miner Electrolyte Metab. 1994;20(5):309-14.
15. Rosenberg J, Pines M, Hurwitz S. Response of adrenal cells to parathyroid hormone stimulation. J Endocrinol. 1987;112(3):431-37. doi: 10.1677/joe.0.1120431
16. Saussine C, Judes C, Massfelder 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. doi: 10.1042/cs0840011
17. 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. doi: 10.1210/endo-129-3-1233
18. Maniero C, Fassina A, Guzzardo V, et al. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension. 2011;58(3):341-6. doi: 10.1161/HYPERTENSIONAHA.111.173948
19. Lenzini L, Prisco S, Vanderriele PE, et al. PTH Modulation by Aldosterone and Angiotensin II is Blunted in Hyperaldosteronism and Rescued by Adrenalectomy. J Clin Endocrinol Metab. 2019;104(9):3726-34. doi: 10.1210/jc.2019-00143
20. Brown J, de Boer IH, Robinson-Cohen C, 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):490-9. doi: 10.1210/jc.2014-3949
21. Fischer E, Hannemann A, Rettig R, 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):965-71. doi: 10.1210/jc.2013-3214
22. Tomaschitz A, Verheyen N, Meinitzer A, 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):1347-56. doi: 10.1097/
HJH.0000000000000927
23. Zaheer S, Brown JM, Connors M, et al. Angiotensin-Converting Enzyme Inhibition and Parathyroid Hormone Secretion. Int J Endocrinol. 2017;2017:4138783. doi: 10.1155/2017/4138783
24. Asbach E, Bekeran M, König A, et al. Primary and Secondary Hyperparathyroidism in Patients with Primary Aldosteronism – Findings From the German Conn’s Registry. Exp Clin Endocrinol Diabetes. 2020;128(4):246-54. doi: 10.1055/a-1027-6472
25. Zhou D, Liu M, Yan Z. Primary aldosteronism complicated by hyperparathyroidism: report of one case and literature review. Int J Clin Exp Pathol. 2019;12(8):3096-101.
26. Concistré A, Petramala L, Zinnamosca L, et al. Primary aldosteronism with concurrent primary hyperparathyroidism: clinical case load in a single centre. Eur Rev Med Pharmacol Sci. 2015;19(6):971-76. https://www.europeanreview.org/article/8681
27. Vaidya A, Brown JM, Williams JS. The renin-angiotensin-aldosterone system and calcium-regulatory hormones. J Hum Hypertens. 2015;29(9):515-21. doi: 10.1038/jhh.2014.125
28. Beysel S, Caliskan M, Kizilgul M, et al. Parathyroidectomy improves cardiovascular risk factors in normocalcemic and hypercalcemic primary hyperparathyroidism. BMC Cardiovasc Disord. 2019;19(1):106. doi: 10.1186/s12872-019-1093-4
29. Bernini G, Moretti A, Lonzi S, et al. Renin-angiotensin-aldosterone system in primary hyperparathyroidism before and after surgery. Metabolism. 1999;48(3):298-300. doi: 10.1016/s0026-0495(99)90075-6
30. Kovacs L, Goth MI, Szabolcs I, et al. The effect of surgical treatment on secondary hyperaldosteronism and relative hyperinsulinemia in primary hyperparathyroidism. Eur J Endocrinol. 1998;138(5):543-47. doi: 10.1530/eje.0.1380543
31. Pacifici R, Perry HM 3rd, Shieber W, et al. Adrenal responses to subtotal parathyroidectomy for primary hyperparathyroidism. Calcif Tissue Int. 1987;41(3):119-23. doi: 10.1007/bf02563790
32. Brunaud L, Germain A, Zarnegar R, et al. Serum aldosterone is correlated positively to parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism. Surgery. 2009;146(6):1035-41. doi: 10.1016/j.surg.2009.09.041
33. Dobreva EA, Bibik EE, Eremkina AK, et al. Correlations between parameters of calcium metabolism and renin-angiotensin-aldosterone system in patients with primary hyperparathyroidism in the pre- and early postoperative periods. Arterial Hypertension. 2019;25(6):630-8 (In Russ.) doi: 10.18705/1607-419X-2019-25-6-630-638
34. Brown JM, Williams JS, Luther JM, et al. Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone. Hypertension. 2014;63(2):273-80. doi: 10.1161/HYPERTENSIONAHA.113.01910
35. DeLuccia R, Cheung M, Ramadoss R, et al. The Endocrine Role of Bone in Cardiometabolic Health. Cur Nutr Rep. 2019;8(3):281-94. doi: 10.1007/s13668-019-00286-0
36. Sorriento D, De Luca N, Trimarco B, Iaccarino G. The Antioxidant Therapy: New Insights in the Treatment of Hypertension. Front Physiol. 2018;9:258. doi: 10.3389/fphys.2018.00258
37. Grubler MR, Marz W, Pilz S, et al. Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence. Rev Endocr Metabc Disord. 2017;18(2):259-72. doi: 10.1007/s11154-017
ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия
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E.A. Dobreva, E.E. Bibik, A.K. Eremkina, A.R. Ajnetdinova, L.V. Nikankina, N.M. Malysheva, N.G. Mokrysheva
Endocrinology Research Centre, Moscow, Russia