Management of Aldosteronism

Laparoscopic adrenalectomy is the current gold standard treatment for unilateral primary aldosteronism, provided that the disease presentation is suitable for surgical treatment.3,9 However, given that unilateral adenomas are responsible for only one-third of sporadic primary aldosterone cases, the limitations of surgical management as first-line treatment for the condition as a whole are evident.3

Patients with bilateral adrenal hyperplasia and those with complex manifestations that extend beyond the scope of surgical resolution are typically treated with long-term pharmaceutical regimens for hypertension control, electrolyte monitoring, and lifestyle modifications.3 Bilateral subtotal adrenalectomies are uncommon and pose a risk of postoperative adrenal insufficiency.3,5

If the RAA ratio suggests primary aldosteronism, imaging suggests a bilateral pathology, and adrenal venous sampling suggests a unilateral predominance of hypersecretion then unilateral adrenalectomy may still be a viable treatment option.2 In this scenario, the adrenal gland responsible for the majority of aldosterone hypersecretion is removed and the mild hyperactivity of the remaining gland is not severe enough to cause symptoms or systemic harm.


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An alternative procedure to adrenalectomy is adrenal ablation via radiofrequency or microwave thermal ablation (MTA). In adrenal ablation, the site of adrenal hyperactivity is located through imaging and the involved tissue is destroyed. Radiofrequency ablation uses electrodes that send currents through the involved tissue resulting in thermal destruction.4 Microwave thermal ablation causes heat through friction that results in tissue destruction.5

Results of a study by Donlon et al suggest that MTA is a more precise form of ablation therapy compared with radiofrequency ablation in patients with bilateral presentation.5 The researchers found that pieces of adrenocortical tissue as small as 0.8 cm3 were successfully ablated with MTA without causing damage to surrounding tissue. In patients with bilateral presentation, this form of therapy offers a precise way to destroy hyperactive tissue without causing lasting bilateral harm to the adrenal system, which could lead to Addison disease.

Hundemer et al performed a retrospective cohort study examining the effects of primary aldosterone management on the risk for developing chronic kidney disease.11 The researchers monitored estimated glomerular filtration rate (eGFR) progression throughout the course of management for 3 groups11:

  1. Patients with primary aldosteronism receiving medical management with mineralocorticoid receptor antagonists (MRAs);
  2. Patients who had undergone surgical adrenalectomy; and
  3. Patients with essential hypertension.

At 5 year follow-up, patients with primary aldosteronism were at a greater risk for developing chronic kidney disease (defined as a decrease in eGFR <60 mL/min per 1.73 m2 plus an overall decline in eGFR from study entry of >15 mL/min per 1.73 m2) compared with the essential hypertension group. However, these numbers were skewed by those patients receiving medical management.11 In fact, no statistically significant difference in chronic kidney risk was found between surgically-treated patients with primary aldosteronism vs patients with essential hypertension.11 The findings not only emphasize the importance of recognizing and diagnosing primary aldosteronism in patients with resistant hypertension, but also suggest that surgical management is more effective at reducing the risk of severe comorbidities than medical management.

A study by Christakis et al involving patients with Conn syndrome found that laparoscopic adrenalectomy was more effective at hypertension control and improving quality of life compared with medical treatment with long-term hypertensive medication.12 Postoperative blood work evaluation indicated an improvement in both serial blood pressure as well as serum potassium abnormalities. Quality of life surveys, scored from 0 to 10, showed a postoperative increase from a median of 6 to a median of 9 in this patient population, and up to 85% of the patients saw a reduction to or cessation of antihypertensive use after surgery.12

Medical Management of Aldosteronism

The most common medication class used for medical treatment is MRAs, and the most commonly used medications in this class are spironolactone and eplerenone.2 The mechanism of action for these medications is competitive binding of mineralocorticoid receptors in the renal distal tubules so that excess aldosterone does not lead to increased retention of sodium and fluid and excessive excretion of potassium.2 Spironolactone is considered the gold standard for treatment because it is the most proficient competitive antagonist to aldosterone in its drug class.2,9 Side effects of spironolactone include fatigue, gastrointestinal upset, and menstrual irregularities. Because of its decreased MRA potency in comparison with aldosterone, eplerenone is considered a second-line treatment and is usually used in patients who experience intolerable side effects to spironolactone therapy.2,9 Potassium-sparing diuretics such as amiloride are used in patients who do not tolerate or do not see improvement with the use of MRAs.2

Papanastasiou et al performed a case-control study on the effect of MRAs on hypertension control in patients with primary aldosterone.13 In 327 hypertensive patients, 28.7% were diagnosed with primary aldosteronism using dexamethasone suppression tests and achieved a statistically significant improvement in both systolic and diastolic blood pressure with the use of spironolactone or eplerenone.13 Patients taking MRAs should be followed routinely with episodic blood pressure checks and blood work review to assess for new or persistent electrolyte abnormalities.

While MRAs are widely regarded as an effective option for hypertension control, the efficacy of these agents in reducing cardiovascular risk is not well established. Results of a retrospective cohort study found an increased risk for cardiac pathology in patients with primary aldosteronism treated with MRAs compared with the risk in patients treated with adrenalectomy.14 The findings provide further support for surgical treatment of primary aldosteronism when possible.

Conclusion

Patients should be educated on symptoms and severe complications that may arise due to poorly controlled aldosteronism. Based on individual presentation, patients should be educated on both surgical and medical treatment options. If they are to be started on MRAs for long-term hypertensive control, the importance of compliance and regular follow-up must be emphasized. For patients recovering from surgery, the reoccurrence or persistence of symptoms could be suggestive of an unresolved state of hormonal imbalance that may need further treatment. The patient’s ability to understand how to monitor their symptoms and comply with treatment plans is essential to establishing quality care.

Lorcan McKillop, PA-C, MPAS, is an endocrinology physician assistant currently working at Endocrine Associates of West Village in New York City, New York. He received his masters of Physician Assistant Studies from Duquesne University in 2020.

Kristin D’Acunto, PA-C, MPAS, is the assistant chair of the Department of Physician Assistant Studies at Duquesne University in Pittsburgh, Pennsylvania. She received her masters of Physician Assistant from Duquesne University in 1997 and is currently pursuing an EdD in Educational Technology.

References

1. Brown JM, Siddiqui M, Calhoun DA, Carey RM, Hopkins PN, Williams GH, 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

2. Papadopoulou-Marketou, N, Vaidya A, Dluhy R, Chrousos GP. Hyperaldosteronism. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. MDText.com, Inc.; 2000-2016.

3. Duan K, Mete O. Clinicopathologic correlates of primary aldosteronism. Arch Pathol Lab Med. 2015;139(7):948-954. doi:10.5858/arpa.2014-0156-RS

4. Sacks BA, Sacks AC, Faintuch S. Radiofrequency ablation treatment for aldosterone-producing adenomas. Curr Opin Endocrinol Diabetes Obes. 2017;24(3):169-173. doi:10.1097/MED.0000000000000329

5. Donlon PT, Fallahi H, Beard WL, et al. Using microwave thermal ablation to develop a subtotal, cortical-sparing approach to the management of primary aldosteronism. Int J Hyperthermia. 2019;36(1):905-914. doi:10.1080/02656736.2019.1650205

6. Byrd JB, Turcu AF, Auchus RJ. Primary aldosteronism: practical approach to diagnosis and management. Circulation. 2018;138(8):823-835. doi:10.1161/CIRCULATIONAHA.118.033597

7. Morimoto R, Omata K, Ito S, Satoh F. Progress in the management of primary aldosteronism. Am J Hypertens. 2018;31(5):522-531. doi:10.1093/ajh/hpy018

8. Baguet JP, Steichen O, Mounier-Véhier C, Gosse P. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 1: Epidemiology of PA, who should be screened for sporadic PA? Ann Endocrinol (Paris). 2016;77(3):187-91. doi:10.1016/j.ando.2016.01.006

9. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF 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

10. Seiler L, Rump LC, Schulte-Mönting J, Slawik M, Borm K, Pavenstädt H, Beuschlein F, Reincke M. Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication. Eur J Endocrinol. 2004;150(3):329-337. doi:10.1530/eje.0.1500329

11. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Renal outcomes in medically and surgically treated primary aldosteronismHypertension. 2018;72(3):658-666. doi:10.1161/HYPERTENSIONAHA.118.11568

12. Christakis I, Livesey JA, Sadler GP, Mihai R. Laparoscopic adrenalectomy for Conn’s syndrome is beneficial to patients and is cost effective in England. J Invest Surg. 2018;31(4):300-306. doi:10.1080/08941939.2017.1323055.

13. Papanastasiou L, Markou A, Pappa T, et al. Primary aldosteronism in hypertensive patients: clinical implications and target therapy. Eur J Clin Invest. 2014;44(8):697-706. doi:10.1111/eci.12286

14. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study. Lancet Diabetes Endocrinol. 2018;6(1):51-59. doi:10.1016/S2213-8587(17)30367-4

This article originally appeared on Clinical Advisor