Первичный гиперпаратиреоз при беременности: современная парадигма диагностики, лечения и неонатального мониторинга

Первичный гиперпаратиреоз во время беременности является редкой, но клинически значимой патологией, сопряженной с высоким риском осложнений как для беременной, так и для плода. Заболевание часто протекает бессимптомно или маскируется физиологическими изменениями фосфорно-кальциевого обмена, что затрудняет своевременную диагностику. Основой биохимической верификации служит выявление паратгормон-зависимой гиперкальциемии. Ультразвуковое исследование шеи является безопасным методом предоперационной локализации патологического очага, в то время как использование радионуклидных и компьютерно-томографических методов ограничено из-за потенциального риска облучения плода. Тактика лечения определяется сроком беременности, выраженностью гиперкальциемии и наличием осложнений. Консервативные методы включают адекватную гидратацию, ограниченное применение кальцитонина и цинакальцета, однако их эффективность ограничена и сопровождается потенциальными рисками для новорожденного. «Золотым» стандартом остается хирургическое лечение – паратиреоидэктомия, оптимально выполняемая во II триместре беременности. Проведение операции ассоциировано со снижением риска самопроизвольных абортов, преждевременных родов, неонатальной гипокальциемии и других осложнений по сравнению с консервативным ведением. Послеродовый период требует динамического наблюдения за пациенткой ввиду возможного резкого повышения уровня кальция в крови. Новорожденные нуждаются в контроле концентрации ионизированного кальция в крови и профилактике неонатальной гипокальциемии.

1. Мокрышева Н.Г., Липатенкова А.К., Таллер Н.А. Первичный гиперпаратиреоз и беременность. Акушерство и гинекология. 2016;(10):18–25. https://doi.org/10.18565/aig.2016.10.18-25.

2. Бибик Е.Е., Еремкина А.К., Князева О.А., Мокрышева Н.Г. Спорадический первичный гиперпаратиреоз с множественной трансформацией околощитовидных желез. Проблемы эндокринологии. 2021;67(6):31–8. https://doi.org/10.14341/probl12798.

3. Mukherjee S., Arya A.K., Bhadada S.K. et al. Characterization of primary hyperparathyroidism based on target organ involvement: an analysis from the Indian PHPT registry. Clin Endocrinol (Oxf). 2023;99(2):158–64. https://doi.org/10.1111/cen.14915.

4. Hirsch D., Kopel V., Nadler V. et al. Pregnancy outcomes in women with primary hyperparathyroidism. J Clin Endocrinol Metab. 2015;100(5):2115–22. https://doi.org/10.1210/jc.2015-1110.

5. Gokkaya N., Gungor A., Bilen A. et al. Primary hyperparathyroidism in pregnancy: a case series and literature review. Gynecol Endocrinol. 2016;32(10):783–6. https://doi.org/10.1080/09513590.2016.1188916.

6. Norman J., Politz D., Politz L. Hyperparathyroidism during pregnancy and the effect of rising calcium on pregnancy loss: a call for earlier intervention. Clin Endocrinol (Oxf). 2009;71(1):104–9. https://doi.org/10.1111/j.1365-2265.2008.03495.x.

7. McMullen T.P., Learoyd D.L., Williams D.C. et al. Hyperparathyroidism in pregnancy: options for localization and surgical therapy. World J Surg. 2010;34(8):1811–6. https://doi.org/10.1007/s00268-010-0569-2.

8. Kokrdova Z. Pregnancy and primary hyperparathyroidism. J Obstet Gynaecol. 2010;30(1):57–9. https://doi.org/10.3109/01443610903315611.

9. Song A., Wang W., Chen S. et al. Primary hyperparathyroidism during pregnancy: a case series of 8 patients. Endocr Pract. 2019;25(11):1127–36. https://doi.org/10.4158/EP-2019-0035.

10. Bhadada S.K., Arya A.K., Mukhopadhyay S. et al. Primary hyperparathyroidism: insights from the Indian PHPT registry. J Bone Miner Metab. 2018;36(2):238–45. https://doi.org/10.1007/s00774-017-0833-8.

11. Pal R., Bhadada S.K., Gupta N. et al. Primary hyperparathyroidism in pregnancy: observations from the Indian PHPT registry. J Endocrinol Invest. 2021;44(7):1425–35. https://doi.org/10.1007/s40618-020-01441-z.

12. Бондаренко А.С., Бибик Е.Е., Воскобойников В.В. и др. Первичный гиперпаратиреоз на фоне беременности, наступившей в результате процедуры экстракорпорального оплодотворения. Акушерство, Гинекология и Репродукция. 2024;18(3):414–24. https://doi.org/10.17749/2313-7347/ob.gyn.rep.2024.458.

13. Som M., Stroup J.S. Primary hyperparathyroidism and pregnancy. Proc (Bayl Univ Med Cent). 2011;24(3):220–3. https://doi.org/10.1080/08998280.2011.11928719.

14. Schnatz P.F., Curry S.L. Primary hyperparathyroidism in pregnancy: evidence-based management. Obstet Gynecol Surv. 2002;57(6):365–76. https://doi.org/10.1097/00006254-200206000-00022.

15. Abood A., Vestergaard P. Pregnancy outcomes in women with primary hyperparathyroidism. Eur J Endocrinol. 2014;171(1):69–76. https://doi.org/10.1530/EJE-13-0966.

16. Arshad M.F., Arambewela M.H., Bennet W.M. et al. Primary hyperparathyroidism in pregnancy: experience of a tertiary centre. Surg Today. 2023;53(4):470–5. https://doi.org/10.1007/s00595-022-02583-8.

17. Бибик Е.Е., Еремкина А.К., Липатенкова Ю.И. и др. Кальций-фосфорный обмен и вспомогательные репродуктивные технологии: точки пересечения. Проблемы репродукции. 2024;30(4):19–28. https://doi.org/10.17116/repro20243004119.

18. Møller U.K., Streym S., Mosekilde L. et al. Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study. Osteoporos Int. 2013;24(4):1307–20. https://doi.org/10.1007/s00198-012-2062-2.

19. Pilz S., Zittermann A., Obeid R. et al. The role of vitamin D in fertility and during pregnancy and lactation: a review of clinical data. Int J Environ Res Public Health. 2018;15(10):2241. https://doi.org/10.3390/ijerph15102241.

20. Григорян О.Р., Михеев Р.К., Волеводз H.H. и др. Эндокринные аспекты функционирования фетоплацентарного комплекса (обзор литературы). Проблемы репродукции. 2017;23(1):15–24. https://doi.org/10.17116/repro201723115-24.

21. Appelman-Dijkstra N.M., Pilz S. Approach to the patient: management of parathyroid diseases across pregnancy. J Clin Endocrinol Metab. 2023;108(6):1505–13. https://doi.org/10.1210/clinem/dgac734.

22. Sant V.R., Zhou H., Zhou M.M. et al. Fertility and pregnancy outcomes in primary hyperparathyroidism: observations from a large insured population. J Clin Endocrinol Metab. 2025;110(5):1427–33. https://doi.org/10.1210/clinem/dgae409.

23. Bilezikian J.P., Khan A.A., Silverberg S.J. et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop. J Bone Miner Res. 2022;37(11):2293–314. https://doi.org/10.1002/jbmr.4677.

24. Augustin G., Lai Q., Berkovic M.C. Primary hyperparathyroidism-induced acute pancreatitis in pregnancy: a systematic review with a diagnostic-treatment algorithm. World J Gastroenterol. 2024;30(32):3755–65. https://doi.org/10.3748/wjg.v30.i32.3755.

25. Hu Y., Cui M., Sun Z. et al. Clinical presentation, management, and outcomes of primary hyperparathyroidism during pregnancy. Int J Endocrinol. 2017;2017:3947423. https://doi.org/10.1155/2017/3947423.

26. Cassir G., Sermer C., Malinowski A.K. Impact of perinatal primary hyperparathyroidism on maternal and fetal and neonatal outcomes: retrospective case series. J Obstet Gynaecol Can. 2020;42(6):750–6. https://doi.org/10.1016/j.jogc.2019.12.017.

27. Свиридонова М.А. Синдром гипокальциурической гиперкальциемии. Редкость ли? Два клинических случая в амбулаторной практике. Проблемы эндокринологии. 2022;68(5):24–31. https://doi.org/10.14341/probl13125.

28. Dochez V., Ducarme G. Primary hyperparathyroidism during pregnancy. Arch Gynecol Obstet. 2015;291(2):259–63. https://doi.org/10.1007/s00404-014-3526-8.

29. Bollerslev J., Rejnmark L., Zahn A. et al. European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders. Eur J Endocrinol. 2022;186(2):R33-R63. https://doi.org/10.1530/EJE-21-1044.

30. Jones A.R., Hare M.J., Brown J. et al. Familial hypocalciuric hypercalcemia in pregnancy: diagnostic pitfalls. JBMR Plus. 2020;4(6):e10362. https://doi.org/10.1002/jbm4.10362.

31. Moghadam R.N., Amlelshahbaz A.P., Namiranian N. et al. Comparative diagnostic performance of ultrasonography and 99mTc-sestamibi scintigraphy for parathyroid adenoma in primary hyperparathyroidism; systematic review and meta-analysis. Asian Pac J Cancer Prev. 2017;18(12):3195–200. https://doi.org/10.22034/APJCP.2017.18.12.3195.

32. Tay D., Das J.P., Yeh R. Preoperative localization for primary hyperparathyroidism: a clinical review. Biomedicines. 2021;9(4):390. https://doi.org/10.3390/biomedicines904039.

33. Becker J.L., Patel V., Johnson K.J. et al. 4D-dynamic contrast-enhanced MRI for preoperative localization in patients with primary hyperparathyroidism. AJNR Am J Neuroradiol. 2020;41(3):522–8. https://doi.org/10.3174/ajnr.A6482.

34. Malheiro E., Chabbert-Buffet N., Talbot J.N., Périé S. Hyperparathyroidism in pregnancy and 99mTc-MIBI scintigraphy. Eur Ann Otorhinolaryngol Head Neck Dis. 2019;136(6):501–3. https://doi.org/10.1016/j.anorl.2019.05.009.

35. Thanseer N., Bhadada S.K., Sood A. et al. Comparative effectiveness of ultrasonography, 99mTc-sestamibi, and 18F-fluorocholine PET/CT in detecting parathyroid adenomas in patients with primary hyperparathyroidism. Clin Nucl Med. 2017;42(12):e491–e497. https://doi.org/10.1097/RLU.0000000000001845.

36. Shah V.N., Shah C.S., Bhadada S.K., Rao D.S. Effect of 25 (OH) D replacements in patients with primary hyperparathyroidism (PHPT) and coexistent vitamin D deficiency on serum 25(OH) D, calcium and PTH levels: a meta-analysis and review of literature. Clin Endocrinol (Oxf). 2014;80(6):797–803. https://doi.org/10.1111/cen.12398.

37. Krysiak R., Wilk M., Okopien B. Recurrent pancreatitis induced by hyperparathyroidism in pregnancy. Arch Gynecol Obstet. 2011;284(3):531–4. https://doi.org/10.1007/s00404-010-1668-x.

38. Hogg P., Thompson M., Burgess J. The clinical expression and impact of multiple endocrine neoplasia 1 during pregnancy. Clin Endocrinol (Oxf). 2020;93(4):429–38. https://doi.org/10.1111/cen.14252.

39. Vera L., Oddo S., Di Iorgi N. et al. Primary hyperparathyroidism in pregnancy treated with cinacalcet: a case report and review of the literature. J Med Case Rep. 2016;10(1):361. https://doi.org/10.1186/s13256-016-1093-2.

40. Horjus C., Groot I., Telting D. et al. Cinacalcet for hyperparathyroidism in pregnancy and puerperium. J Pediatr Endocrinol Metab. 2009;22(8):741–9. https://doi.org/10.1515/jpem.2009.22.8.741.

41. Rey E., Jacob C.E., Koolian M., Morin F. Hypercalcemia in pregnancy – a multifaceted challenge: case reports and literature review. Clin Case Rep. 2016;4(10):1001–8. https://doi.org/10.1002/ccr3.646.

42. Foster E., Maalouf N.M. Use of cinacalcet for the management of primary hyperparathyroidism in pregnancy. JCEM Case Rep. 2024;2(7):luae117. https://doi.org/10.1210/jcemcr/luae117.

43. Rubin M.R., Silverberg S.J. Use of cinacalcet and 99mTc-sestamibi imaging during pregnancy. J Endocr Soc. 2017;1(9):1156–9. https://doi.org/10.1210/js.2017-00308.

44. Green S.B., Pappas A.L. Effects of maternal bisphosphonate use on fetal and neonatal outcomes. Am J Health Syst Pharm. 2014;71(23):2029–36. https://doi.org/10.2146/ajhp140041.

45. Losada I., Sartori L., Di Gianantonio E. et al. Bisphosphonates in patients with autoimmune rheumatic diseases: can they be used in women of childbearing age? Autoimmun Rev. 2010;9(8):547–52. https://doi.org/10.1016/j.autrev.2010.03.002.

46. Boyce R.W., Varela A., Chouinard L. et al. Infant cynomolgus monkeys exposed to denosumab in utero exhibit an osteoclast-poor osteopetrotic-like skeletal phenotype at birth and in the early postnatal period. Bone. 2014;64:314–25. https://doi.org/10.1016/j.bone.2014.04.002.

47. Yamaguchi M, Takami M, Azetsu Y, et al. Effects of anti-RANKL antibodies administered to pregnant mice on bone and tooth development in neonates. J Oral Biosci. 2023;65(2):186–94. https://doi.org/10.1016/j.job.2023.03.001.

48. Sandler M.L., Ho R., Xing M.H. et al. Primary hyperparathyroidism during pregnancy treated with parathyroidectomy: a systematic review. Laryngoscope. 2021;131(8):1915–21. https://doi.org/10.1002/lary.29489.

49. Eli S., Gal S.G., Adnan Z. Comparison between surgical and non-surgical management of primary hyperparathyroidism during pregnancy: a systematic review. Endocrine. 2024;86(1):101–8. https://doi.org/10.1007/s12020-024-03930-0.

50. Irvin G.L., Solorzano C.C., Carneiro D.M. Quick intraoperative parathyroid hormone assay: surgical adjunct to allow limited parathyroidectomy, improve success rate, and predict outcome. World J Surg. 2004;28(12):1287–92. https://doi.org/10.1007/s00268-004-7708-6.

51. Ahmadieh H., Kreidieh O., Akl E.A. et al. Minimally invasive parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IOPTH) and preoperative imaging versus bilateral neck exploration for primary hyperparathyroidism in adults. Cochrane Database Syst Rev. 2020;10(10):CD010787. https://doi.org/10.1002/14651858.CD010787.pub2.

52. Rigg J., Gilbertson E., Barrett H.L. et al. Primary hyperparathyroidism in pregnancy: maternofetal outcomes at a quaternary referral obstetric hospital, 2000 through 2015. J Clin Endocrinol Metab. 2019;104(3):721–9. https://doi.org/10.1210/jc.2018-01104.

53. Wei Y., Peng L., Li Y. et al. Clinical study on safety and efficacy of microwave ablation for primary hyperparathyroidism. Korean J Radiol. 2020;21(5):572–81. https://doi.org/10.3348/kjr.2019.0593.

54. Wei Y., Peng C.Z., Wang S.R. et al. Effectiveness and safety of thermal ablation in the treatment of primary hyperparathyroidism: a multicenter study. J Clin Endocrinol Metab. 2021;106(9):2707–17. https://doi.org/10.1210/clinem/dgab240.

55. Ospina N.S., Thompson G.B., Lee R.A. et al. Safety and efficacy of percutaneous parathyroid ethanol ablation in patients with recurrent primary hyperparathyroidism and multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2015;100(1):E87–90. https://doi.org/10.1210/jc.2014-3255.

56. Bansal S., Kaushik R.M., Kaushik R. et al. Primary hyperparathyroidism presenting as severe hypercalcemia with acute pancreatitis in pregnancy. Gynecol Endocrinol. 2020;36(5):469–72. https://doi.org/10.1080/09513590.2019.1698028.

57. Luo Y., Lv Q., Xu Z. et al. Case report: microwave ablation is a safe and effective method for primary hyperparathyroidism in pregnancy. Front Med (Lausanne). 2024;11:1204696. https://doi.org/10.3389/fmed.2024.1204696.

58. Lemaitre M., Picart C., Gueorguieva I. et al. Chapter 7: The different forms of primary hyperparathyroidism at different ages of life: Childhood, pregnancy, lactation, old age. Ann Endocrinol (Paris). 2025;86(1):101696. https://doi.org/10.1016/j.ando.2025.101696.

59. Рожинская Л.Я., Белая Ж.Е., Луценко А.С. Новые возможности лечения вторичного гиперпаратиреоза у пациентов с терминальной стадией хронической болезни почек, получающих заместительную почечную терапию гемодиализом. Остеопороз и остеопатии. 2017;20(1):32–8. https://doi.org/10.14341/osteo2017126-33.

60. Carbonare L.D., Valenti M.T., Del Forno F. et al. Vitamin D: daily vs. monthly use in children and elderly-what is going on? Nutrients. 2017;9(7):652. https://doi.org/10.3390/nu9070652.