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Problems of diagnosis and treatment of Connshing syndrome

https://doi.org/10.30629/0023-2149-2024-102-4-367-374

Abstract

Despite the fact that it has been almost 50 years since the first description of aldosterone-cortisol-producing adrenal adenomas (Connshing syndrome), there are still many unresolved issues regarding the diagnosis and treatment of this condition. The presented clinical case confirms the complexity of recognizing this disease due to the frequent absence of its manifesting clinical symptoms and the lack of information acquired from standard laboratory tests. In these cases, the method of comparative selective venous blood sampling from the adrenal glands plays a significant role in the differential diagnosis of rare forms of primary hyperaldosteronism. Analysis of clinical cases presented in the scientific literature from 2000 to 2023 showed that partial adrenalectomy is the method of choice for surgical treatment of this pathology, which is associated with minimal risk of postoperative complications.

About the Authors

M. S. Annaev
Far Eastern Federal University
Russian Federation

Meilis S. Annaev — graduate student of the School of Medicine and Life Sciences

Vladivostok


B. I. Geltser
Far Eastern Federal University
Russian Federation

Boris I. Geltser — Dr. of Sci. (Med.), Professor, Corresponding Member of RAS, Deputy Director for Research, School of Medicine and Life Sciences

 

Vladivostok


K. V. Stegniy
Far Eastern Federal University
Russian Federation

Kirill V. Stegniy — Dr. of Sci. (Med.), Professor, Corresponding Member of RAS, Professor of the Department of Residency and Continuing Education, School of Medicine and Life Sciences

Vladivostok


O. I. Pak
Far Eastern Federal University
Russian Federation

Oleg I. Pak — Cand. of Sci. (Med.), doctor of the highest category, chief physician of the Medical Complex

Vladivostok


R. A. Goncharuk
Far Eastern Federal University
Russian Federation

Roman A. Goncharuk — Cand. of Sci. (Med.), surgeon, oncologist, Medical Complex

Vladivostok


S. M. Selyutin
Far Eastern Federal University
Russian Federation

Sergey M. Selyutin — doctor of X-ray endovascular diagnostic methods and treatment, Department of Cardiac Surgery and Vascular Surgery, Medical Complex

Vladivostok


A. M. Morozova
Far Eastern Federal University
Russian Federation

Alla M.Morozova — Cand. of Sci. (Med.),, Associate Professor of the Department of Continuing Education and Residency, School of Medicine and Life Sciences

Vladivostok


O. G. Tsygankova
Regional Clinical Hospital № 2
Russian Federation

Olga G. Tsygankova — head of the Primorsky Regional Center for Diabetes and Endocrine Diseases of the State Budgetary Healthcare Institution Сity Сlinical Hospital No. 2, chief freelance specialist endocrinologist of the Ministry of Health of the Primorye Territory

Vladivostok


E. V. Maslyantsev
Far Eastern Federal University
Russian Federation

Evgeniy V. Maslyantsev — assistant of the Department of Clinical Medicine of the School of Medicine and Life Sciences, surgeon at the Surgery Center of the Medical Complex

Vladivostok


V. G. Fisenko
Far Eastern Federal University
Russian Federation

Vasiliy G. Fisenko — intensivist of the department of anesthesiology, resuscitation and intensive care of the Medical Complex

Vladivostok


References

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

2. Melnichenko G.A., Platonova N.M., Beltsevich D.G., Yukina M. Yu., 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. J. Consilium Medicum. 2017;19(4):75–85. (In Russian).

3. 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

4. Mulatero P., Monticone S., Deinum J., Amar L., Prejbisz A., Zennaro M.C., Beuschlein F., Rossi G.P., Nishikawa T., Morganti A., Seccia T.M., Lin Y.H., Fallo F., Widimsky J. Genetics, prevalence, screening and confi rmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension. J. Hypertens. 2020;38(10):1919–1928. DOI: 10.1097/HJH.0000000000002510

5. Brown J.M., Siddiqui M., Calhoun D.A., Carey R.M., Hopkins P.N., Williams G.H., Vaidya A. The unrecognized prevalence of primary aldosteronism: a cross-sectional study. Ann. Intern. Med. 2020;173(1):10–20. DOI: 10.7326/M20-0065.

6. Funder J.W., Carey R.M. Primary Aldosteronism: Where Are We Now? Where to From Here? Hypertension. 2022;79(4):726–735. DOI: 10.1161/HYPERTENSIONAHA.121.18761

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

8. William Ya., 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

9. Hogan M.J., Schambelan M., Biglieri E.G. Concurrent hypercortisolism and hypermineralocorticoidism. Am. J. Med. 1977;62(5):777 –82. DOI: 10.1016/0002-9343(77)90883-x

10. Arlt W., Lang K., Sitch A.J., Dietz A.S., Rhayem Y., Bancos I., Feuchtinger A., Chortis V., Gilligan L.C., Ludwig P., Riester A., Asbach E., Hughes B.A., O’Neil D.M., Bidlingmaier M., Tomlinson J.W., Hassan-Smith Z.K., Rees D.A., Adolf C., Hahner S., Quinkler M., Dekkers T., Deinum J., Biehl M., Keevil B.G., Shackleton C.H., Deeks J.J., Walch A.K., Beuschlein F., Reincke M. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight. 2017 20;2(8):e93136. DOI: 10.1172/jci.insight.93136. PMID: 28422753; PMCID: PMC5396526

11. Rossi G.P., Auchus R.J., Brown M., Lenders J.W., Naruse M., Plouin P.F., Satoh F., Young W.F. Jr. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension. 2014;63(1):151–60. DOI: 10.1161/HYPERTENSIONAHA.113.02097

12. Piaditis G.P., Kaltsas G.A., Androulakis I.I., Gouli A., Makras P., Papadogias D., Dimitriou K., Ragkou D., Markou A., Vamvakidis K., Zografos G., Chrousos G. High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas. Clin. Endocrinol. (Oxf). 2009;71(6):772–8. DOI: 10.1111/j.1365-2265.2009.03551.x

13. Hiraishi K., Yoshimoto T., Tsuchiya K., Minami I., Doi M., Izumiyama H., Sasano H., Hirata Y. Clinicopathological features of primary aldosteronism associated with subclinical Cushing’s syndrome. Endocr. J. 2011;58(7):543–51. DOI: 10.1507/endocrj.k10e-402

14. Tang L., Li X., Wang B., Ma X., Li H., Gao Y., Gu L., Nie W., Zhang X. Clinical Characteristics of Aldosterone- and Cortisol-Coproducing Adrenal Adenoma in Primary Aldosteronism. Int. J. Endocrinol. 2018;2018:4920841. DOI: 10.1155/2018/4920841

15. Shifman B.M., Platonova N.M., Molashenko N.V., Troshina E.A., Romanova N.Yu., Kolesnikova G.S. Aldosterone- and cortisol-co-secreting adrenal tumors: an uneasy sum of well-known parts (review). Problemy Endokrinologii. 2019;65(2):113–123. (In Russian). DOI: org/10.14341/probl10036

16. Peng K.Y., Liao H.W., Chan C.K., Lin W.C., Yang S.Y., Tsai Y.C., Huang K.H., Lin Y.H., Chueh J.S., Wu V.C. Presence of Subclinical Hypercortisolism in Clinical Aldosterone-Producing Adenomas Predicts Lower Clinical Success. Hypertension. 2020;76(5):1537–1544. DOI: 10.1161/HYPERTENSIONAHA.120.15328. Epub 2020 Sep 14. PMID: 32921192

17. Späth M., Korovkin S., Antke C., Anlauf M., Willenberg H.S. Aldosterone- and cortisol-co-secreting adrenal tumors: the lost subtype of primary aldosteronism. Eur. J. Endocrinol. 2011;164(4):447–55. DOI: 10.1530/EJE-10-1070

18. 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.

19. Goupil R., Wolley M., Ungerer J., McWhinney B., Mukai K., Naruse M., Gordon R.D., Stowasser M. Use of plasma metanephrine to aid adrenal venous sampling in combined aldosterone and cortisol over-secretion. Endocrinol. Diabetes Metab. Case Rep. 2015;2015:150075. DOI: 10.1530/EDM-15-0075

20. Kishino M., Yoshimoto T., Nakadate M., Katada Y., Kanda E., Nakaminato S., Saida Y., Ogawa Y., Tateishi U. Optimization of left adre nal vein sampling in primary aldosteronism: Coping with asymmetrical cortisol secretion. Endocr. J. 2017;64(3):347–355. DOI: 10.1507/endocrj.EJ16-0433

21. Rossijskaja associacija endokrinologov i nejrohirurgov. Bolezn’ Icenko–Kushinga. Klinicheskie rekomendacii. Moscow: Ministerstvo zdravoohranenija Rossijskoj Federacii; 2016. (In Russian).

22. Zhang Y., Tan J., Yang Q., Du Z., Yang S., He W., Song Y., Hu J., Yang Y., Li Q., Zhang Y., He Y., Cheng Q. Chongqing Primary Aldosteronism Study (CONPASS) Group. Primary aldosteronism concurrent with subclinical Cushing’s syndrome: a case report and review of the literature. J. Med. Case Rep. 2020;14(1):32. DOI: 10.1186/s13256-020-2353-8

23. Zhao L., Wan J., Wang Y., Yang W., Liang Q., Wang J., Jin P. Diff erent cell compositions and a novel somatic KCNJ5 variant found in a patient with bilateral adrenocortical adenomas secreting aldosterone and cortisol. Front Endocrinol. (Lausanne). 2023;14:1068335. DOI: 10.3389/fendo.2023.1068335

24. Chen Y.J., Peng K.Y., Chueh J.S., Liao H.W., Hsieh T.Y., Wu V.C., Wang S.M. Case Report: Primary Aldosteronism Due to Bilateral Aldosterone-Producing Micronodules With HISTALDO Classical and Contralateral Non-Classical Pathology. Front Endocrinol. (Lausanne). 2022;13:816754. DOI: 10.3389/fendo.2022.816754

25. Ren K., Wei J., Liu Q., Zhu Y., Wu N., Tang Y., Li Q., Zhang Q., YuY., An Z., Chen J., Li J. Hypercortisolism and primary aldostero nism caused by bilateral adrenocortical adenomas: a case report. BMC Endocr. Disord. 2019;19(1):63. DOI: 10.1186/s12902-019-0395-y

26. Onoda N., Ishikawa T., Nishio K., Tahara H., Inaba M., Wakasa K., Sumi T., Yamazaki T., Shigematsu K., Hirakawa K. Cushing’s syndrome by left adrenocortical adenoma synchronously associated with primary aldosteronism by right adrenocortical adenoma: report of a case. Endocr. J. 2009;56(3):495–502. DOI: 10.1507/endocrj. k08e-268

27. Lee S.E., Kim J.H., Lee Y.B., Seok H, Shin I.S., Eun Y.H., Kim J.H., Oh Y.L. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently. Endocrinol. Metab. (Seoul). 2015;30(4):607– 13. DOI: 10.3803/EnM.2015.30.4.607

28. Honda T., Nakamura T., Saito Y., Ohyama Y., Sumino H., Kurabayashi M. Combined primary aldosteronism and preclinical Cushing’s syndrome: an unusual case presentation of adrenal adenoma. Hypertens. Res. 2001;24(6):723–6. DOI: 10.1291/hypres.24.723

29. Hu L, Ji W., Guo M., Yi T., Wang J., Bao M., Gao Y., Jin H., Lu D., Ma W., Han X., Li J., Yuan Z. Case Report: Primary Aldosteronism and Subclinical Cushing Syndrome in a 49-Year-Old Woman With Hypertension Plus Hypokalaemia. Front Cardiovasc. Med. 2022;9:911333. DOI: 10.3389/fcvm.2022.911333

30. Morimoto R., Kudo M., Murakami O., Takase K., Ishidoya S., Nakamura Y., Ishibashi T., Takahashi S., Arai Y., Suzuki T., Sasano H., Ito S., Satoh F. Diffi cult-to-control hypertension due to bilateral aldosterone-producing adrenocortical microadenomas associated with a cortisol-producing adrenal macroadenoma. J. Hum. Hypertens. 2011;25(2):114-21. DOI: 10.1038/jhh.2010.35

31. Kukidome D., Miyamura N., Sakakida K., Shimoda S., Shigematu Y., Nishi K., Yamashita Y., Eto M., Sasano H., Araki E. A case of cortisol producing adrenal adenoma associated with a latent aldosteronoma: usefulness of the ACTH loading test for the detection of covert aldosteronism in overt Cushing syndrome. Intern. Med. 2012;51(4):395–400. DOI: 10.2169/internalmedicine.51.5597

32. Fushimi Y., Tatsumi F., Sanada J., Shimoda M., Kamei S., Nakanishi S., Kaku K., Mune T., Kaneto H. Concurrence of overt Cushing’s syndrome and primary aldosteronism accompanied by aldosterone-producing cell cluster in adjacent adrenal cortex: case report. BMC Endocr. Disord. 2021;21(1):163. DOI: 10.1186/s12902-021-00818-2

33. Goupil R., Wolley M., Ungerer J., McWhinney B., Mukai K., Naruse M., Gordon R.D., Stowasser M. Use of plasma metanephrine to aid adrenal venous sampling in combined aldosterone and cortisol over-secretion. Endocrinol. Diabetes Metab. Case Rep. 2015;2015:150075. DOI: 10.1530/EDM-15-0075

34. Fujii H., Kamide K., Miyake O., Abe T., Nagai M., Nakahama H., Horio T., Takiuchi S., Okuyama A., Yutani C., Kawano Y. Primary aldosteronism combined with preclinical Cushing’s syndrome in an elderly patient. Circ. J. 2005;69(11):1425-7. DOI: 10.1253/circj.69.1425

35. Chang K.Y., Ryu S., Cho J.Y., Kim H.W. Aldosterone- and cortisol-co-producing adrenal adenoma without clinical features of Cushing syndrome. Korean J. Intern. Med. 2014;29(5):67982. DOI: 10.3904/kjim.2014.29.5.679

36. Hu Z., Chen X., Shao Y., Luo F.X., Chu S.L., Wang J.G. Hypertension with unilateral adrenal aldosterone and cortisol cosecreting adenoma: A case report. J. Clin. Hypertens (Greenwich). 2021;23(11):1987–1991. DOI: 10.1111/jch.14374

37. Yoon V., Heyliger A., Maekawa T., Sasano H., Carrick K., Woodruff S., Rabaglia J., Auchus R.J., Ghayee H.K. Benign adrenal adenomas secreting excess mineralocorticoids and glucocorticoids. Endocrinol. Diabetes Metab. Case Rep. 2013;2013:130042. DOI: 10.1530/EDM-13-0042

38. 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

39. 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

40. 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

41. 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

42. 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

43. 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

44. 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


Review

For citations:

Annaev M.S., Geltser B.I., Stegniy K.V., Pak O.I., Goncharuk R.A., Selyutin S.M., Morozova A.M., Tsygankova O.G., Maslyantsev E.V., Fisenko V.G. Problems of diagnosis and treatment of Connshing syndrome. Clinical Medicine (Russian Journal). 2024;102(4):367-374. (In Russ.) https://doi.org/10.30629/0023-2149-2024-102-4-367-374

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ISSN 0023-2149 (Print)
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