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Postoperative adrenal insufficiency in Conn’s syndrome—does it occur frequently?

Journal of Human Hypertension volume 36, pages 510–516 (2022)Cite this article

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Abstract

Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Recently, frequent clinically significant adrenal insufficiency after adrenalectomy in subjects with PA has been reported, which may make the early postsurgical management difficult. We retrospectively searched for possible adrenal insufficiency in subjects who underwent adrenalectomy for PA and have measured cortisol in the early postoperative course. We included subjects with confirmed diagnosis of PA who underwent either posture testing (blood draw at 06:00 and 08:00) and/or adrenal venous sampling (AVS) (blood draw between 08:00 and 09:00) and have also measured cortisol after surgery (cortisol measured approximately at 07:00). Cortisol was measured by immunoassay. In this study, we identified 150 subjects (age 48.5 ± 10.3 years) with available cortisol values in the early postoperative course (median [25th percentile, 75th percentile]) 6 [5,6] days. Postoperative cortisol values (551 ± 148 nmol/l) were normal and significantly higher, compared to preoperative standing cortisol values (404 ± 150 nmol/l; (P < 0.001) and AVS cortisol values (493 ± 198 nmol/l; P = 0.009), and did not significantly differ from preoperative supine cortisol values. Postsurgical cortisol values were not different among subjects with or without abnormal dexamethasone suppression test or elevated urinary free cortisol pre-surgery, and were significantly higher in subjects with abnormal diurnal cortisol variability compared with subjects with normal diurnal variability. No patient presented with adrenocortical crisis in the later follow-up. In conclusion, postoperative cortisol values did not indicate any suspicion of possible adrenal insufficiency. To exclude possible adrenal insufficiency, it may be sufficient to measure morning cortisol in the early postoperative course.

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Fig. 1: Comparison of cortisol value after adrenalectomy with different preoperative cortisol values (linear mixed model with random intercept).
Fig. 2: Comparison of postoperative cortisol values among subjects with or without abnormalities in cortisol metabolism.

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References

  1. Widimský J, Bruthans J, Wohlfahrt P, Krajčoviechová A, Šulc P, Linhart A, et al. Primary aldosteronism in a general population sample. The Czech post-MONICA study. Blood Press. 2020;29:191–8.

    Article  Google Scholar 

  2. Kayser SC, Deinum J, de Grauw WJ, Schalk BW, Bor HJ, Lenders JW, et al. Prevalence of primary aldosteronism in primary care: a cross-sectional study. Br J Gen Pract. 2018;68:e114–e122.

    Article  Google Scholar 

  3. Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol. 2017;69:1811–20.

    Article  Google Scholar 

  4. Štrauch B, Zelinka T, Hampf M, Bernhardt R, Widimský J Jr. Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region. J Hum Hypertens. 2003;17:349–52.

    Article  Google Scholar 

  5. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101:1889–916.

    Article  CAS  Google Scholar 

  6. Walz MK, Groeben H, Alesina PF. Single-access retroperitoneoscopic adrenalectomy (SARA) versus conventional retroperitoneoscopic adrenalectomy (CORA): a case-control study. World J Surg. 2010;34:1386–90.

    Article  Google Scholar 

  7. Mulatero P, Sechi LA, Williams TA, Lenders JWM, Reincke M, Satoh F, et al. Subtype diagnosis, treatment, complications and outcomes of primary aldosteronism and future direction of research: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens. 2020;38:1929–36.

    Article  CAS  Google Scholar 

  8. Heinrich DA, Adolf C, Holler F, Lechner B, Schneider H, Riester A, et al. Adrenal insufficiency after unilateral adrenalectomy in primary aldosteronism: long-term outcome and clinical impact. J Clin Endocrinol Metab. 2019;104:5658–64.

    Article  Google Scholar 

  9. Honda K, Sone M, Tamura N, Sonoyama T, Taura D, Kojima K, et al. Adrenal reserve function after unilateral adrenalectomy in patients with primary aldosteronism. J Hypertens. 2013;31:2010–7.

    Article  CAS  Google Scholar 

  10. Fallo F, Bertello C, Tizzani D, Fassina A, Boulkroun S, Sonino N, et al. Concurrent primary aldosteronism and subclinical cortisol hypersecretion: a prospective study. J Hypertens. 2011;29:1773–7.

    Article  CAS  Google Scholar 

  11. O’Toole SM, Sze WC, Chung TT, Akker SA, Druce MR, Waterhouse M, et al. Low-grade cortisol cosecretion has limited impact on ACTH-stimulated AVS parameters in primary aldosteronism. J Clin Endocrinol Metab. 2020;105:e3776–e3784.

    Article  Google Scholar 

  12. Arlt W, Lang K, Sitch AJ, Dietz AS, Rhayem Y, Bancos I, et al. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight. 2017;2:e93136.

    Article  Google Scholar 

  13. Gerards J, Heinrich DA, Adolf C, Meisinger C, Rathmann W, Sturm L, et al. Impaired glucose metabolism in primary aldosteronism is associated with cortisol cosecretion. J Clin Endocrinol Metab. 2019;104:3192–202.

    Article  Google Scholar 

  14. Holaj R, Zelinka T, Wichterle D, Petrák O, Štrauch B, Widimský J Jr. Increased intima-media thickness of the common carotid artery in primary aldosteronism in comparison with essential hypertension. J Hypertens. 2007;25:1451–7.

    Article  CAS  Google Scholar 

  15. Holaj R, Rosa J, Zelinka T, Štrauch B, Petrák O, Indra T, et al. Long-term effect of specific treatment of primary aldosteronism on carotid intima-media thickness. J Hypertens. 2015;33:874–82. discussion 882.

    Article  CAS  Google Scholar 

  16. Phillips JL, Walther MM, Pezzullo JC, Rayford W, Choyke PL, Berman AA, et al. Predictive value of preoperative tests in discriminating bilateral adrenal hyperplasia from an aldosterone-producing adrenal adenoma. J Clin Endocrinol Metab. 2000;85:4526–33.

    Article  CAS  Google Scholar 

  17. Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017;5:689–99.

    Article  Google Scholar 

  18. Zelinka T, Widimský J. Twenty-four hour blood pressure profile in subjects with different subtypes of primary aldosteronism. Phys Res. 2001;50:51–7.

    CAS  Google Scholar 

  19. Fontes RG, Kater CE, Biglieri EG, Irony I. Reassessment of the predictive value of the postural stimulation test in primary aldosteronism. Am J Hypertens. 1991;4:786–91.

    Article  CAS  Google Scholar 

  20. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:1526–40.

    Article  CAS  Google Scholar 

  21. Bates D, Machler M, Bolker BM, Walker SC. Fitting linear mixed-effects models using lme4. J Stat Soft. 2015;67:1–48.

    Article  Google Scholar 

  22. Manosroi W, Phimphilai M, Khorana J, Atthakomol P. Diagnostic performance of basal cortisol level at 0900-1300h in adrenal insufficiency. PLoS One. 2019;14:e0225255.

    Article  CAS  Google Scholar 

  23. Schmidt IL, Lahner H, Mann K, Petersenn S. Diagnosis of adrenal insufficiency: evaluation of the corticotropin-releasing hormone test and Basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. J Clin Endocrinol Metab. 2003;88:4193–8.

    Article  CAS  Google Scholar 

  24. Mackenzie SD, Gifford RM, Boyle LD, Crane MS, Strachan MWJ, Gibb FW. Validated criteria for the interpretation of a single measurement of serum cortisol in the investigation of suspected adrenal insufficiency. Clin Endocrinol. 2019;91:608–15.

    Article  CAS  Google Scholar 

  25. Sbardella E, Isidori AM, Woods CP, Argese N, Tomlinson JW, Shine B, et al. Baseline morning cortisol level as a predictor of pituitary-adrenal reserve: a comparison across three assays. Clin Endocrinol. 2017;86:177–84.

    Article  CAS  Google Scholar 

  26. Zaman S, Almazrouei R, Sam AH, DiMarco AN, Todd JF, Palazzo FF, et al. Synacthen stimulation test following unilateral adrenalectomy needs to be interpreted with caution. Front Endocrinol. 2021;12:654600.

    Article  Google Scholar 

  27. Prete A, Yan Q, Al-Tarrah K, Akturk HK, Prokop LJ, Alahdab F, et al. The cortisol stress response induced by surgery: a systematic review and meta-analysis. Clin Endocrinol. 2018;89:554–67.

    Article  Google Scholar 

  28. Khawandanah D, ElAsmar N, Arafah BM. Alterations in hypothalamic-pituitary-adrenal function immediately after resection of adrenal adenomas in patients with Cushing’s syndrome and others with incidentalomas and subclinical hypercortisolism. Endocrine. 2019;63:140–8.

    Article  CAS  Google Scholar 

  29. Wang D, Li HZ, Zhang YS, Wang L, Ji ZG. Is prophylactic steroid treatment mandatory for subclinical cushing syndrome after unilateral laparoscopic adrenalectomy? Surg Laparosc Endosc Percutan Technol. 2019;29:31–5.

    Article  Google Scholar 

  30. Di Dalmazi G, Berr CM, Fassnacht M, Beuschlein F, Reincke M. Adrenal function after adrenalectomy for subclinical hypercortisolism and Cushing’s syndrome: a systematic review of the literature. J Clin Endocrinol Metab. 2014;99:jc20141401.

    Article  Google Scholar 

  31. Fallo F, Pilon C, Williams TA, Sonino N, Morra Di Cella S, Veglio F, et al. Coexistence of different phenotypes in a family with glucocorticoid-remediable aldosteronism. J Hum Hypertens. 2004;18:47–51.

    Article  CAS  Google Scholar 

  32. Yasuda S, Hikima Y, Kabeya Y, Iida S, Oikawa Y, Isshiki M, et al. Clinical characterization of patients with primary aldosteronism plus subclinical Cushing’s syndrome. BMC Endocr Disord. 2020;20:9.

    Article  CAS  Google Scholar 

  33. Hiraishi K, Yoshimoto T, Tsuchiya K, Minami I, Doi M, Izumiyama H, et al. Clinicopathological features of primary aldosteronism associated with subclinical Cushing’s syndrome. Endocr J. 2011;58:543–51.

    Article  CAS  Google Scholar 

  34. Peng KY, Liao HW, Chan CK, Lin WC, Yang SY, Tsai YC, et al. Presence of subclinical hypercortisolism in clinical aldosterone-producing adenomas predicts lower clinical success. Hypertension. 2020;76:1537–44.

    Article  CAS  Google Scholar 

  35. Williams TA, Gomez-Sanchez CE, Rainey WE, Giordano TJ, Lam AK, Marker A, et al. International histopathology consensus for unilateral primary aldosteronism. J Clin Endocrinol Metab. 2021;106:42–54.

    Article  Google Scholar 

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Funding

This study was supported by research projects of the Charles University Progres Q25 and Q28 and by the research grant of the Ministry of Health of the Czech Republic #NV19-01-00083.

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Authors and Affiliations

  1. Center of Hypertension, 3rd Department of Medicine—Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Tomáš Zelinka, Ondřej Petrák, Matěj Zítek, Robert Holaj & Jiří Widimský Jr.

  2. Department of Anesthesiology, 3rd Faculty of Medicine, Charles University and University Hospital Královské Vinohrady in Prague, Prague, Czech Republic

    Petr Waldauf

  3. Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Lubomíra Forejtová

  4. 1st Department of Surgery, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    David Michalský

  5. Department of Urology, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic

    Květoslav Novák

  6. Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Jaroslava Dušková

  7. Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Drahomíra Springer

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  1. Tomáš Zelinka
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Contributions

TZ: Study design, data acquisition, data analysis, writing manuscript. OP, MZ, RH, JW: Data acquisition, critical manuscript revision. PW: Statistics, critical manuscript revision. LF: Adrenal venous sampling, critical manuscript revision. DM, KN: Adrenal surgery, critical manuscript revision. JD: Histopathological analysis, critical manuscript revision. DS: Biochemical analysis, critical manuscript revision

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Correspondence to Tomáš Zelinka.

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The authors declare no competing interests.

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Previous presentation: Part of the study was presented as an oral presentation during the ON-AIR ESH-ISH Joint Meeting 2021.

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Zelinka, T., Petrák, O., Waldauf, P. et al. Postoperative adrenal insufficiency in Conn’s syndrome—does it occur frequently?. J Hum Hypertens 36, 510–516 (2022). https://doi.org/10.1038/s41371-021-00618-0

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  • DOI: https://doi.org/10.1038/s41371-021-00618-0

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