Primary aldosteronism and pregnancy




pregnancy, primary aldosteronism, arterial hypertension, diuretics


The article is devoted to a review of scientific publications that study primary aldosteronism (PA), as well as its features during pregnancy. PA is the most common cause of secondary hypertension. There are few data on PA during pregnancy. PA is characterized by excessive production of aldosterone, which leads to hemodynamic changes in the body, especially the appearance of hypertension. Studies in recent years have shown that up to 88% of adenomas may have gene mutations involved in the regulation of aldosterone synthesis: KCNJ5, CACNA1D, ATP1A1, ATP2B3 and CTNNB1. PA is a renin-independent hypersecretion of aldosterone, which remains an underdiagnosed cause of hypertension. Early diagnosis and treatment contribute to the favorable course of this disease.
Changes in renin-angiotensin-aldosterone activity during pregnancy may delay diagnosis. The risk of combined preeclampsia in patients diagnosed with PA may be even higher than in women with chronic primary hypertension with an estimated risk of approximately 17–25%. Given the lack of treatment standards, the management of pregnancies described in scientific publications is different.
However, given current knowledge, the following recommendations are possible:
• pregnancy should be programmed, and PA should be monitored as much as possible without the use of spironolactone before pregnancy;
• adrenalectomy should be performed if unilateral adrenal damage is found before pregnancy;
• antihypertensive drugs approved for use during pregnancy, such as methyldopa, β-blockers, should be used during pregnancy planning;
• spironolactone should be discontinued before conception.
It can be used a diuretic that was prescribed before pregnancy, or prescribed the diuretic in a situation of uncontrolled hypertension.
The article also presents our own clinical case of three pregnancies in one woman with PA, their course and outcome. Only the first pregnancy was complicated by preeclampsia, and PA was diagnosed 5 years after the first birth. All pregnancies ended with the birth of living, full-term babies.

Author Biographies

V.I. Medved, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”, Kyiv

MD, professor, corresponding member of the NAMS of Ukraine, head of the Department of Internal Pathology of Pregnant Woman

M.Y. Kyrylchuk, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”, Kyiv

MD, chief research fellow, Department of Internal Pathology of Pregnant Woman

A.Y. Husieva, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”, Kyiv

Junior research fellow, Department of Internal Pathology of Pregnant Woman


  1. Dick, S.M., Queiroz, M., Bernardi, B.L., et al. “Update in diagnosis and management of primary aldosteronism.” Clin Chem Lab Med 56.3 (2018): 360–72.
  2. Litynski, M. “Hypertension caused by tumors of the adrenal cortex.” Pol Tyg Lek (Wars) 8.6 (1953): 204–8.
  3. Conn, J.W. “Presidential address. I. Painting background. II. Primary aldosteronism, a new clinical syndrome.” J Lab Clin Med 45 (1955): 3–17.
  4. Käyser, S.C., Deinum, J., de Grauw, W.J., et al. “Prevalence of primary aldosteronism in primary care: a cross-sectional study.” Br J Gen Pract 68.667 (2018): e114–22.
  5. Monticone, S., Burrello, J., Tizzani, D., et al. “Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice.” J Am Coll Cardiol 69.14 (2017): 1811–20.
  6. Štrauch, B., Zelinka, T., Hampf, M., et al. “Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region.” J Hum Hypertens 17.5 (2003): 349–52.
  7. Mills, K.T., Bundy, J.D., Kelly, T.N., et al. “Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries.” Circulation 134 (2016): 441–50.
  8. Camelli, S., Bobrie, G., Postel-Vinay, N., et al. “Prevalence of secondary hypertension in young hypertensive adults.” J Hypertens 33 (2015): e47.
  9. Stowasser, M., Gordon, R.D. “Primary aldosteronism: changing definitions and new concepts of physiology and pathophysiology both inside and outside the kidney.” Physiol Rev 96 (2016): 1327–84.
  10. Brown, J.M., Siddiqui, M., Calhoun, D.A., et al. “The unrecognized prevalence of primary aldosteronism: a cross-sectional study.” Ann Intern Med 173 (2020): 10–20.
  11. Pizzolo, F., Zorzi, F., Chiecchi, L., et al. “NT-proBNP, a useful tool in hypertensive patients undergoing a diagnostic evaluation for primary aldosteronism.” Endocrine 45.3 (2014): 479–86.
  12. Li, J., Kubbar, A., Kim, E., et al. “Primary Hyperaldosteronism in Pregnancy: A Case Report.” J Endocrine Soc 5.1 (2021): A153–4.
  13. Hundemer, G.L., Curhan, G.C., Yozamp, N., et al. “Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study.” Lancet Diabetes Endocrinol 6 (2018): 51–9.
  14. Brown, J.M., Robinson-Cohen, C., Luque-Femandez, M.A., et al. “The spectrum of subclinical primary aldosteronism and incident hypertension: a cohort study.” Ann Intern Med 167 (2017): 630–41.
  15. Vasan, R.S., Evans, J.C., Larson, M.G., et al. “Serum aldosterone and the incidence of hypertension in nonhypertensive persons.” N Engl J Med 351 (2004): 33–41.
  16. Williams, B., MacDonald, T.M., Morant, S., et al. “Spironolactone versus placebo, isoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomized, double-blind, crossover trial.” Lancet 386 (2015): 2059–68.
  17. Williams, B., MacDonald, T.M., Morant, S., et al. “Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies.” Lancet Diabetes Endocrinol 6 (2018): 464–75.
  18. Vaidya, A., Mulatero, P., Baudrand, R., et al. “The expanding spectrum of primary aldosteronism: implications for diagnosis, pathogenesis and treatment.” Endocr Rev 39 (2018): 1057–88.
  19. Mulatero, P., Monticone, S., Burrello, J., et al. “Guidelines for primary aldosteronism: uptake by primary care physicians in Europe.” J Hypertens 34 (2016): 2253–7.
  20. Mulatero, P., Tizzani, D., Viola, A., et al. “Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms).” Hypertension 58 (2011): 797–803.
  21. Nanba, K., Omata, K., Else, T., et al. “Targeted Molecular Characterization of Aldosterone-Producing Adenomas in White Americans.” J Clin Endocrinol Metab 103.10 (2018): 3869–76.
  22. Dutta, R.K., Söderkvist, P., Gimm, O. “Genetics of primary hyperaldosteronism.” Endocr Relat Cancer 23.10 (2016): R437–54.
  23. Ashley B. Grossman. Primary Aldosteronism (Conn Syndrome). MSD Manual, Sep 2020.
  24. Funder, J.W., Carey, R.M., Mantero, F., et al. “The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline.” J Clin Endocrinol Metab 101 (2016): 1889–916.
  25. Rossi, G.P., Auchus, R.J., Brown, M., et al. “An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism.” Hypertension 63.1 (2014): 151–60. DOI: 10.1161/HYPERTENSIONAHA.113.02097
  26. Ruhle, B.C., White, M.G., Alsafran, S., et al. “Keeping primary aldosteronism in mind: deficiencies in screening at-risk hypertensives.” Surgery 165 (2019): 221–7.
  27. Jaffe, G., Gray, Z., Krishnan, G., et al. “Screening rates for primary aldosteronism in resistant hypertension: a cohort study.” Hypertension 75 (2020): 650–9.
  28. Burello, J., Monicone, S., Losano, I., et al. “Prevalence of hypokalemia and primary aldosteronism in 5100 patients referred to a tertiary hypertension unit.” Hypertension 75 (2020): 1025–33.
  29. Monticone, S., D’Ascenzo, F., Moretti, C., et al. “Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis.” Lancet Diabetes Endocrinol 6 (2018): 41–50.
  30. Te Riet, L., van Esch, J.H., Roks, A.J., et al. “Hypertension: renin-angiotensin-aldosterone system alterations.” Circ Res 116 (2015): 960–75.
  31. Malha, L., August, P. “Secondary hypertension in pregnancy.” Curr Hypertens Rep 17 (2015): 563.
  32. Landau, E., Amar, L. “Primary aldosteronism and pregnancy.” Ann Endocrinol (Paris) 77.2 (2016): 148–60.
  33. Broughton Pipkin, F. “The renin-angiotensin system in pregnancy: why bother?” Br J Obstet Gynaecol 89 (1982): 591–3.
  34. Rosenfeld, C.R. “Mechanisms regulating angiotensin II responsiveness by the uteroplacental circulation.” Am J Physiol Regul Integr Comp Physiol 281 (2001): R1025–40.
  35. Fujiyama, S., Mori, Y., Matsubara, H., et al. “Primary aldosteronism with aldosterone-producing adrenal adenoma in a pregnant woman.” Intern Med 38 (1999): 36–9.
  36. Franks, R.C., Hayashi, R.H. “Maternal and fetal renin activity and renin and big renin concentrations in second-trimester pregnancy.” Am J Obstet Gynecol 134 (1979): 20–2.
  37. Symonds, E.M., Craven, D.J., Rodeck, C.H. “Fetal plasma renin and renin substrate in mid-trimester pregnancy.” Br J Obstet Gynaecol 92 (1985): 618–21.
  38. Eschler, D.C., Kogekar, N., Pessah-Pollack, R. “Management of adrenal tumors in pregnancy.” Endocrinol Metab Clin North Am 44 (2015): 381–97.
  39. West, C.A., Sasser, J.M., Baylis, C. “The enigma of continual plasma volume expansion in pregnancy: critical role of the renin-angiotensin-aldosterone system.” Am J Physiol Renal Physiol 311.6 (2016): F1125–34.
  40. Keely, E. “Endocrine causes of hypertension in pregnancy – when to start looking for zebras.” Semin Perinatol 22 (1998): 471–84.
  41. Nursal, T.Z., Caliskan, K., Ertorer, E., et al. “Laparoscopic treatment of primary hyperaldosteronism in a pregnant patient.” Can J Surg 52 (2009): E188–90.
  42. Gagnon, N., Cáceres-Gorriti, K.Y., Corbeil, G., et al. “Genetic Characterization of GnRH/LH-Responsive Primary Aldosteronism.” J Clin Endocrinol Metab 103.8 (2018): 2926–35.
  43. Ronconi, V., Turchi, F., Zennaro, M.-C., et al. “Progesterone increase counteracts aldosterone action in a pregnant woman with primary aldosteronism.” Clin Endocrinol (Oxf) 74 (2011): 278–9.
  44. Colton, R., Perez, G.O., Fishman, L.M. “Primary aldosteronism in pregnancy.” Am J Obstet Gynecol 150 (1984): 892–3.
  45. Shigematsu, K., Nishida, N., Sakai, H., et al. “Primary aldosteronism with aldosterone-producing adenoma consisting of pure zona glomerulosa-type cells in a pregnant woman.” Endocr Pathol 20 (2009): 66–72.
  46. Al-Ali, N.A., El-Sandabesee, D., Steel, S.A., Roland, J.M. “Conn’s syndrome in pregnancy successfully treated with amiloride.” J Obstet Gynaecol 27 (2007): 730–1.
  47. Kosaka, K., Onoda, N., Ishikawa, T., et al. “Laparoscopic adrenalectomy on a patient with primary aldosteronism during pregnancy.” Endocr J 53 (2006): 461–6.
  48. Abdelmannan, D., Aron, D.C. “Adrenal disorders in pregnancy.” Endocrinol Metab Clin North Am 40 (2011): 779–94.
  49. Verdonk, K., Visser, W., Van Den Meiracker, A.H., Danser, A.H. “The renin-angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad.” Clinical Science 126 (2014): 537–44.
  50. American College of Obstetricians and Gynecologists. “Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy.” Obstet Gynecol 122.5 (2013) 1122–31.
  51. Seely, E.W., Ecker, J. “Chronic hypertension in pregnancy.” Circulation 129.11 (2014): 1254–61.
  52. Brown, M.A., Gallery, E.D. “Volume homeostasis in normal pregnancy and pre-eclampsia: physiology and clinical implications.” Baillieres Clin Obstet Gynaecol 8.2 (1994): 287–310.
  53. Herse, F., LaMarca, B. “Angiotensin II type 1 receptor autoantibody (AT1-AA)-mediated pregnancy hypertension.” Am J Reprod Immunol 69 (2013): 413–8.
  54. Rossitto, G., Regolisti, G., Rossi, E., et al. “Elevation of angiotensin-II type-1-receptor autoantibodies titer in primary aldosteronism as a result of aldosterone-producing adenoma.” Hypertension 61 (2013): 526–33.
  55. Kem, D.C., Li, H., Velarde-Miranda, C., et al. “Autoimmune mechanisms activating the angiotensin AT1 receptor in primary aldosteronism.” J Clin Endocrinol Metab 99 (2014): 1790–7.
  56. Riester, A., Reincke, M. “Progress in primary aldosteronism: mineralocorticoid receptor antagonists and management of primary aldosteronism in pregnancy.” Eur J Endocrinol 172.1 (2015): R23–30.
  57. Morton, A., Panitz, B., Bush, A. “Eplerenone for gitelman syndrome in pregnancy.” Nephrology (Carlton) 16 (2011): 349.
  58. Hutter, D.A., Berkowitz, R., Davis, S.E., Ashtyani, H. “Application of continuous positive airway pressure in hypoxemic acute respiratory failure associated with diastolic dysfunction in pregnancy.” Congest Heart Fail 12 (2006): 174–5.
  59. Cabassi, A., Rocco, R., Berretta, R., et al. “Eplerenone use in primary aldosteronism during pregnancy.” Hypertension 59 (2012): e18–9.
  60. Zelinka, T., Petrák, O., Rosa, J., et al. “Primary Aldosteronism and Pregnancy.” Kidney Blood Press Res 45.2 (2020): 275–85. DOI: 10.1159/000506287
  61. Okawa, T., Asano, K., Hashimoto, T., et al. “Diagnosis and management of primary aldosteronism in pregnancy: case report and review of the literature.” Am J Perinatol 19 (2002): 31–6.



How to Cite

Medved, V., Kyrylchuk, M., & Husieva, A. (2022). Primary aldosteronism and pregnancy. REPRODUCTIVE ENDOCRINOLOGY, (63-64), 39–46.



Treatment of infertility and pregnancy