What is the management of primary hyperaldosteronism (Conn's syndrome)?

From the Guidelines

The management of hyperaldosteronism should prioritize a targeted approach based on whether the condition is primary or secondary, with unilateral primary hyperaldosteronism being best treated with laparoscopic adrenalectomy, and bilateral disease or patients who cannot undergo surgery being treated with mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, as recommended by the most recent guidelines 1.

Key Considerations

• Primary hyperaldosteronism is the most common form of secondary hypertension, and its management depends on its subtype, particularly on adrenal lesions being unilateral or bilateral 1.
• For unilateral primary aldosteronism, surgical removal of the offending adrenal gland is typically considered, unless the patient is older or has co-morbidities of concern 1.
• Medical treatment is currently based on MRAs, with spironolactone being the most widely available, and eplerenone being an alternative with fewer antiandrogenic side effects 1.

Treatment Approach

• Unilateral disease is best treated with laparoscopic adrenalectomy, which can cure or significantly improve hypertension in most patients 1.
• For bilateral disease or patients who cannot undergo surgery, mineralocorticoid receptor antagonists are the cornerstone of medical therapy, with spironolactone typically started at 25-50 mg daily and titrated up to 100-400 mg daily based on blood pressure response and potassium levels 1.
• Eplerenone (50-100 mg daily) is an alternative with fewer antiandrogenic side effects, and newer agents, such as finerenone and exarenone, and the aldosterone synthase inhibitor baxdrostat, are also being tested for treating primary aldosteronism 1.

Monitoring and Follow-up

• All patients should be monitored for electrolyte abnormalities, particularly hyperkalemia, when on mineralocorticoid receptor antagonists 1.
• Dietary sodium restriction to less than 2.4 g daily can enhance the effectiveness of both surgical and medical treatments, and blood pressure should be monitored regularly, with additional antihypertensive medications being needed to achieve target blood pressure goals 1.

From the FDA Drug Label

2.5 Treatment of Primary Hyperaldosteronism Administer spironolactone tablets in doses of 100 mg to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone tablets can be used as long-term maintenance therapy at the lowest effective dosage determined for the individual patient. 1.4 Primary Hyperaldosteronism Spironolactone tablets are indicated in the following settings: Short-term preoperative treatment of patients with primary hyperaldosteronism. Long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery Long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).

The management of primary hyperaldosteronism involves the use of spironolactone in doses of 100 mg to 400 mg daily. This can be used for:

• Short-term preoperative treatment of patients with primary hyperaldosteronism.
• Long-term maintenance therapy for patients who are not candidates for surgery, including those with:
  • Discrete aldosterone-producing adrenal adenomas
  • Bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism) 2 2.

From the Research

Diagnosis and Treatment of Hyperaldosteronism

• Primary hyperaldosteronism is a prevalent condition, affecting approximately 5-13% of hypertensive patients 3, 4.
• The diagnosis of primary aldosteronism involves imaging and adrenal venous sampling to lateralize hyperaldosteronism, with unilateral disease treated by adrenalectomy and bilateral disease treated by mineralocorticoid receptor antagonists and conventional antihypertensives 3.
• The aldosterone-to-renin ratio is the most sensitive screening test for primary aldosteronism, and confirmatory tests such as the furosemide test may be used 5.

Medical Management

• Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, are used to treat primary aldosteronism, with a starting dose of 12.5-25mg/day spironolactone and titration up to 100mg/day 6.
• Additional treatment with potassium-sparing diuretics or calcium channel antagonists may be necessary if blood pressure is not normalized by first-line treatment 6.
• New therapeutic approaches include the use of low-dose spironolactone in first-line therapy for hypertension and the development of aldosterone synthase inhibitors and other alternative treatments 3, 4.

Surgical Management

• Unilateral laparoscopic adrenalectomy is the preferential treatment for patients with aldosterone-producing adenomas, and bilateral hyperplasia should be treated with mineralocorticoid antagonists 5.
• New surgical approaches, such as robot-assisted laparoscopic adrenalectomy and percutaneous computed tomography radiofrequency ablation, have been developed 4.

Multidisciplinary Approach

• Recognizing and treating primary aldosteronism requires a multidisciplinary approach with primary care physicians, cardiologists, endocrinologists, and radiologists working collaboratively 7.
• Lifestyle modifications, including dietary salt restriction and appropriate calorie intake, play a crucial role in suppressing overactivation of the mineralocorticoid receptor and controlling blood pressure 4.