Primary hyperaldosteronism: the choice in favor of conservative surgery

Primary hyperaldosteronism (PHA) is the most common cause of secondary arterial hypertension among endocrine disorders.  Given that patients with this pathology are at a higher risk of developing fatal and non-fatal cardiovascular events, early  diagnosis and timely treatment are of great importance. Currently, the two main forms of PHA are aldosterone-producing  adenoma and bilateral adrenal hyperplasia, which are treated with laparoscopic adrenalectomy or pharmacotherapy with  mineralocorticoid receptor antagonists. Although most patients experience restoration of their functional and metabolic  status after surgical intervention, some may develop postoperative adrenal insuffi ciency, which requires long-term hormone  replacement therapy. This review examines the options for organ-preserving surgeries, such as partial adrenalectomy and  selective embolization of the adrenal artery.

1. Beltsevich D.G., Troshina E.A., Melnichenko G.A., Platonova N.M., Ladygina D.O., Sheve A. Draft of the clinical practice guidelines “adrenal incidentaloma”. J. Endocrine Surgery. 2021;15(1):4–26. (In Russian)]. DOI: org/10.14341/serg12712

2. Chatzellis E., Kaltsas G. Adrenal Incidentalomas. 2019 Nov 7. In: Feingold K.R., Anawalt B., Blackman M.R., Boyce A., Chrousos G., Corpas E., de Herder W.W., Dhatariya K., Hofl and J., Dungan K., Hofl and J., Kalra S., Kaltsas G., Kapoor N., Koch C., Kopp P., Korbonits M., Kovacs C.S., Kuohung W., Laferrère B., Levy M., McGee E.A., McLachlan R., New M., Purnell J., Sahay R., Singer F., Sperling M.A., Stratakis C.A., Trence D.L., Wilson D.P., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.

3. Muradyan A.G., Kostin A.A., Vorobiov N.V., Tolkachev A.O. Metastatic adrenal tumors. Epidemiology, etiology, diagnosis. P.A. Herzen Journal of Oncology = Onkologiya. Zhurnal im. P.A. Gertsena. 2020;9(3):53–60. (In Russian). DOI: 10.17116/onkolog2020903153

4. Young W., Ladygina D.O., Balutina O.V., Beltsevich D.G. Primary aldosteronism: The Mayo clinic approach. Therapeutic Archive. 2020;92(10):83–87. (In Russian). DOI: 10.26442/00403660.2020.10.000754

5. Melnichenko G.A., Platonova N.M., Beltsevich D.G., Yukina I., Molashenko N.V., Troshina E.A. Primary hyperaldosteronism: diagnosis and treatment. A new look at the problem. According to the materials of the Russian Association of Endocrinologists clinical guidelines for primary hyperaldosteronism diagnosis and treatment. Consilium Medicum. 2017;19(4):75–85. (In Russian).

6. Huang W.C., Lin Y.H., Wu V.C., Chen C.H., Siddique S., Chia Y.C., Tay J.C., Sogunuru G., Cheng H.M., Kario K. Who should be screened for primary aldosteronism? A comprehensive review of current evidence. J. Clin. Hypertens. (Greenwich). 2022;24(9):1194– 1203. DOI: 10.1111/jch.14558

7. Monticone S., D'Ascenzo F., Moretti C., Williams T.A., Veglio F., Gaita F., Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6(1):41–50. DOI: 10.1016/S2213-8587(17)30319-4

8. Khamnueva L.Yu., Andreeva L.S., Tokareva N.P., Novozhilov A.V., Efi mov A.A., Rozhanskaya E.V. Diagnosis and treatment of aldosterone-producing adenoma in a young patient: a clinical case. Clinical Medicine Almanac. 2021;49(5):335– 341 (In Russian). DOI: 10.18786/2072-0505-2021-49-039

9. Hiramatsu K., Yamada T., Yukimura Y., Komiya I., Ichikawa K., Ishihara M., Nagata H., Izumiyama T. A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients. Arch. Intern. Med. 1981;141(12):1589–93. DOI:10.1001/archinte.1981.00340130033011

10. Gan W., Lin W., Ouyang J., Li Y., Chen D., Yao Z., Feng P. High effi ciency of the aldosterone-to-renin ratio in precisely detecting primary aldosteronism. J. Hum. Hypertens. 2019;33(1):57–61. DOI: 10.1038/s41371-018-0112-8

11. Schilbach K., Junnila R.K., Bidlingmaier M. Aldosterone to Renin Ratio as Screening Tool in Primary Aldosteronism. Exp. Clin. Endocrinol. Diabetes. 2019;127(02–03):84–92. DOI: 10.1055/a-0672-0836

12. Ariens J., Horvath A.R., Yang J., Choy K.W. Performance of the aldosterone-to-renin ratio as a screening test for primary aldosteronism in primary care. Endocrine. 2022;77(1):11–20. DOI: 10.1007/s12020-022-03084-x

13. Hung A., Ahmed S., Gupta A., Davis A., Kline G.A., Leung A.A., Ruzicka M., Hiremath S., Hundemer G.L. Performance of the Aldosterone to Renin Ratio as a Screening Test for Primary Aldosteronism. J. Clin. Endocrinol. Metab. 2021;106(8):2423–2435. DOI: 10.1210/clinem/dgab348

14. Chikhladze N.M. Primary hyperaldosteronism: indications for screening. Therapeutic Archive. 2022;94(1):107–113. (In Russian). DOI: 10.2 6442/00403660.2022.01.201324

15. Stowasser M., Ahmed A.H., Pimenta E., Taylor P.J., Gordon R.D. Factors aff ecting the aldosterone/renin ratio. Horm. Metab. Res. 2012;44(3):170–6. DOI: 10.1055/s-0031-1295460

16. Alnazer R.M., Veldhuizen G.P., Kroon A.A., de Leeuw P.W. The effect of medication on the aldosterone-to-renin ratio. A critical review of the literature. J. Clin. Hypertens. (Greenwich). 2021;23(2):208– 214. DOI: 10.1111/jch.14173

17. Veldhuizen G.P., Alnazer R.M., Kroon A.A., de Leeuw P.W. Confounders of the aldosterone-to-renin ratio when used as a screening test in hypertensive patients: A critical analysis of the literature. J. Clin. Hypertens. (Greenwich). 2021;23(2):201–207. DOI: 10.1111/jch.14117

18. Funder J.W., Carey R.M., Mantero F., Murad M.H., Reincke M., Shibata H., Stowasser M., Young W.F. Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2016;101(5):1889–916. DOI: 10.1210/jc.2015-4061

19. Naruse M., Katabami T., Shibata H., Sone M., Takahashi K., Tanabe A., Izawa S., Ichijo T., Otsuki M., Omura M., Ogawa Y., Oki Y., Kurihara I., Kobayashi H., Sakamoto R., Satoh F., Takeda Y., Tanaka T., Tamura K., Tsuiki M., Hashimoto S., Hasegawa T., Yoshimoto T., Yoneda T., Yamamoto K., Rakugi H., Wada N., Saiki A., Ohno Y., Haze T. Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021. Endocr. J. 2022;69(4):327-359. DOI: 10.1507/endocrj.EJ21-0508

20. Russmann M.L. E., Delfi no L., Fierro F., Santoro S., Peréz M., Caruso G., Glikman P., Gauna A., Lupi S. Primary aldosteronism: Aldosterone/renin ratio cut-off points. Endocrinol. Diabetes Nutr. (Engl. Ed.). 2019;66(6):361–367. English, Spanish. DOI: 10.1016/j.endinu.2018.11.008

21. Yoon M., Hong N., Ha J., Lee CJ., Ku C.R., Rhee Y., Park S. Prevalence and clinical characteristics of primary aldosteronism in a tertiary-care center in Korea. Hypertens. Res. 2022;45(9):1418–1429. DOI: 10.1038/s41440-022-00948-7

22. Kempers M.J., Lenders J.W., van Outheusden L., van der Wilt G.J., Schultze Kool L.J., Hermus A.R., Deinum J. Systematic review: diagnostic procedures to diff erentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. J. Ann. Intern. Med. 2009;151(5):329–37. DOI: 10.7326/0003-4819-151-5-200909010-00007

23. Ladurner R., Sommerey S., Buechner S., Dietz A., Degenhart C., Hallfeldt K., Gallwas J. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism. Eur. J. Clin. Invest. 2017;47(5):372–377. DOI: 10.1111/eci.12746

24. Betz M.J., Zech C.J. Adrenal venous sampling in the diagnostic workup of primary aldosteronism. Br. J. Radiol. 2022;95(1129):20210311. DOI: 10.1259/bjr.20210311

25. Addison T. on the constitutional and local eff ects of disease of the supra-renal capsules. London, UK: Samuel Highley; 1855.

26. Barthel A., Benker G., Berens K., Diederich S., Manfras B., Gruber M., Kanczkowski W., Kline G., Kamvissi-Lorenz V., Hahner S., Beuschlein F., Brennand A., Boehm B.O., Torpy D.J., Bornstein S.R. An Update on Addi’on's Disease. J. Exp. Clin. Endocrinol. Diabetes. 2019;127(2-03):165–175. DOI: 10.1055/a-0804-2715

27. Di Dalmazi G., Berr C.M., Fassnacht M., Beuschlein F., Reincke M. Adrenal function after adrenalectomy for subclinical hypercortisolism and Cush’ng's syndrome: a systematic review of the literature. J. Clin. Endocrinol. Metab. 2014;99(8):2637–45. DOI: 10.1210/jc.2014-1401

28. Kulshreshtha B., Arora A., Aggarwal A., Bhardwaj M. Prolonged adrenal insuffi ciency after unilateral adrenalectomy for Cush’ng's Syndrome. Indian J. Endocrinol Metab. 2015;19(3):430–2. DOI: 10.4103/2230-8210.152794

29. Fischer E., Hanslik G., Pallauf A., Degenhart C., Linsenmaier U., Beuschlein F., Bidlingmaier M., Mussack T., Ladurner R., Hallfeldt K., Quinkler M., Reincke M. Prolonged zona glomerulosa insuffi ciency causing hyperkalemia in primary aldosteronism after adrenalectomy. J. Clin. Endocrinol. Metab. 2012;97(11):3965–73. DOI: 10.1210/jc.2012-2234

30. Park K.S., Kim J.H., Ku E.J., Hong A.R., Moon M.K., Choi S.H., Shin C.S., Kim S.W., Kim S.Y. Clinical risk factors of postoperative hyperkalemia after adrenalectomy in patients with aldosterone-producing adenoma. Eur. J. Endocrinol. 2015;172(6):725–31. DOI: 10.1530/EJE-15-0074

31. Heinrich D.A., Adolf C., Holler F., Lechner B., Schneider H., Riester A., Nirschl N., Sturm L., Wang X., Ladurner R., Seidensticker M., Bidlingmaier M., Beuschlein F., Reincke M. Adrenal insuffi ciency after unilateral adrenalectomy in primary aldosteronism: long-term outcome and clinical impact. J. Clin. Endocrinol. Metab. 2019;104(11):5658–5664. DOI: 10.1210/jc.2019-00996

32. Alesina P.F., Knyazeva P., Hinrichs J., Walz M.K. Tailored Approach in Adrenal Surgery: Retroperitoneoscopic Partial Adrenalectomy. Front Endocrinol. (Lausanne). 2022;13:855326. DOI: 10.3389/fendo.2022.855326. PMID: 35418944; PMCID: PMC8995530

33. Brauckhoff M., Stock K., Stock S., Lorenz K., Sekulla C., Brauckhoff K., Thanh P.N., Gimm O., Spielmann R.P., Dralle H. Limitations of intraoperative adrenal remnant volume measurement in patients undergoing subtotal adrenalectomy. World J. Surg. 2008;32(5):86372. DOI: 10.1007/s00268-007-9402-y

34. Walz M.K. Nebennierenresektion zum Erhalt der adrenokortikalen Funktion. Indikationen und Ergebnisse [Adrenalectomy for preservation of adrenocortical function. Indication and results]. Chirurg. 2009;80(2):99–104. German. DOI: 10.1007/s00104-008-1612-9

35. Li K.P., Duan X., Yang X.S., Huang J., Wu T. Partial versus total adrenalectomy for the treatment of unilateral aldosterone-producing adenoma: a systematic review and meta-analysis. Updates Surg. 2021;73(6):2301–2313. DOI: 10.1007/s13304-021-01116-1

36. Miron A., Giulea C., Nădrăgea M., Enciu O Laparoscopic Partial Adrenalectomy. Chirurgia (Bucur). 2017;112(1):77–81. DOI: 10.21614/chirurgia.112.1.77

37. Miron A., Toma E.A., Enciu O. Partial adrenalectomy — how far can we go? Acta Endocrinol. (Buchar). 2022;18(3):401–405. DOI: 10.4183/aeb.2022.401

38. Billmann F., Billeter A., Thomusch O., Keck T., El Shishtawi S., Langan E.A., Strobel O., Müller-Stich B.P. Minimally invasive partial versus total adrenalectomy for unilateral primary hyperaldosteronism-a retrospective, multicenter matched-pair analysis using the new international consensus on outcome measures. Surgery. 2021;169(6):1361–1370. DOI: 10.1016/j.surg.2020.09.005

39. Balescu I., Arnautu O., Grasu M., Badiu C., Tomulescu V., Copăescu C. Partial adrenalectomy — arguments for the minimally invasive surgical approach. Chirurgia (Bucur). 2019;114(5):611–621. DOI: 10.21614/chirurgia.114.5.611

40. Procopio P.F., Pennestrì F., De Crea C., Voloudakis N., Bellantone R., Raff aelli M. Outcome of Partial Adrenalectomy in MEN2 Syndrome: Personal Experience and Systematic Review of Literature. Life (Basel). 2023;13(2):425. DOI: 10.3390/life13020425

41. Flammia R.S., Anceschi U., Tufano A., Bologna E., Proietti F., Bove A.M., Misuraca L., Mastroianni R., Tirone G., Carrara A., Luciani L., Cai T., Leonardo C., Simone G. Minimally Invasive Partial vs. Total Adrenalectomy for the Treatment of Unilateral Primary Aldosteronism: A Systematic Review and Meta-Analysis. J. Clin. Med. 2022;11(5):1263. DOI: 10.3390/jcm11051263

42. Van de Wiel E.C.J., Küsters B., Mann R., Veltien A., Aalders T.W., Verhaegh G.W., Mukai K., Deinum J., Langenhuijsen J.F. Partial adrenalectomy carries a considerable risk of incomplete cure in primary aldosteronism. J. Urol. 2021;206(2):219–228. DOI: 10.1097/JU.0000000000001752

43. Takumi K., Kanako K.K., Masao O., Tomoko T., Yuya T., Haremaru K., Yuto Ya., Hironobu S., Jun S., Tetsuo N. Precise mapping of intra-adrenal aldosterone activities provides a novel surgical strategy for primary aldosteronism. J. Hypertension. 2020;76:976–984. DOI: 10.1161/hypertensionaha.119.14341

44. Zhou Y., Wang D., Liu Q., Hou J., Wang P. Case report: Percutaneous adrenal arterial embolization cures resistant hypertension. Front Cardiovasc. Med. 2022;9:1013426. DOI: 10.3389/fcvm.2022.1013426

45. Van der Walt I.S., Brown M., Lodh S. Adrenal gland-sparing transcatheter embolisation of an aldosteronoma for the treatment of refractory hypertension. Radiol. Case Rep. 2022;17(4):1088–1094. DOI: 10.1016/j.radcr.2022.01.043

46. Dong H., Zou Y., He J., Deng Y., Chen Y., Song L., Xu B., Gao R., Jiang X. Superselective adrenal arterial embolization for idiopathic hyperaldosteronism: 12-month results from a proof-of-principle trial. Catheter Cardiovasc. Interv. 2021;97(2):976–981. DOI: 10.1002/ccd.29554

47. Ishikawa T., Morimoto S., Ichihara A. Eff ects of mineralocorticoid receptor antagonists on sex hormones and body composition in patients with primary aldosteronism. Hypertens. Res. 2022;45(3):496– 506. DOI: 10.1038/s41440-021-00836-6

48. Qiu J., Li N., Xiong H.L., Yang J., Li Y.D., Hu C.K., Lai Z.Q., Liang N.P., Zhang H.J., Jiang X.J., Dong Y.F. Superselective adrenal arterial embolization for primary aldosteronism without lateralized aldosterone secretion: an effi cacy and safety, proof-of-principle study. Hypertens. Res. 2023 Mar 3. DOI: 10.1038/s41440-023-01236-8

49.