Primary aldosteronism is a disorder caused by autonomous production of aldosterone by the adrenal cortex (due to hyperplasia, adenoma, or carcinoma). Symptoms and signs include episodic weakness, elevated blood pressure, and hypokalemia. Diagnosis includes measurement of plasma aldosterone levels and plasma renin activity. Treatment depends on cause. A tumor is removed if possible; in hyperplasia, spironolactone or related medications may normalize blood pressure and eliminate other clinical features.
(See also Overview of Adrenal Function.)
Aldosterone is the most potent mineralocorticoid produced by the adrenal cortex. It causes sodium retention and potassium loss. In the kidneys, aldosterone causes transfer of sodium from the lumen of the distal tubule into the tubular cells in exchange for potassium and hydrogen. The same effect occurs in salivary glands, sweat glands, cells of the intestinal mucosa, and in exchanges between intracellular fluid (ICF) and extracellular fluid (ECF).
Aldosterone secretion is regulated by the renin-angiotensin system and, to a lesser extent, by adrenocorticotropic hormone (ACTH). Renin, a proteolytic enzyme, is stored in the juxtaglomerular cells of the kidneys. Reduction in blood volume and flow in the afferent renal arterioles or hyponatremia induces secretion of renin. Renin transforms angiotensinogen from the liver to angiotensin I, which is transformed by angiotensin-converting enzyme (ACE) to angiotensin II, which in turn causes secretion of aldosterone. Sodium retention and water retention resulting from increased aldosterone secretion increase the blood volume and reduce renin secretion.
Primary aldosteronism is caused by an:
Adrenal adenoma, usually unilateral, of the glomerulosa or fasciculata cells of the adrenal cortex
Adrenal carcinoma or hyperplasia (rare)
Adenomas are extremely rare in children, but primary aldosteronism sometimes occurs in childhood adrenal carcinoma or adrenal hyperplasia.
In adrenal hyperplasia, which is more common among older males, both adrenals are overactive, and no adenoma is present. The clinical picture can also occur with certain forms of congenital adrenal hyperplasia (in which other mineralocorticoids are elevated) and the dominantly inherited dexamethasone-suppressible hyperaldosteronism.
Small aldosterone-secreting adenomas are increasingly recognized as a cause of primary hypertension (in up to 10% of patients with hypertension) even when serum potassium levels are normal (1).
General reference
1. Ekman N, Grossman AB, Dworakowska D. What We Know about and What Is New in Primary Aldosteronism. Int J Mol Sci. 2024;25(2):900. doi:10.3390/ijms25020900
Symptoms and Signs of Primary Aldosteronism
Diastolic hypertension and hypokalemic nephropathy with polyuria and polydipsia are common.
Hypernatremia, hypervolemia, and a hypokalemic alkalosis may occur, causing episodic weakness, paresthesias, transient paralysis, and tetany.
In many cases, the only manifestation is hypertension, which may vary from mild to severe but is often resistant to conventional therapy.
Edema is uncommon.
Diagnosis of Primary Aldosteronism
Electrolytes
Plasma aldosterone
Plasma renin activity (PRA)
Adrenal imaging
Bilateral adrenal vein catheterization (for cortisol and aldosterone levels)
Primary aldosteronism is suspected in patients with hypertension and hypokalemia but increasingly is being diagnosed in patients with normokalemia and resistant hypertension.
Initial laboratory testing consists of plasma aldosterone levels and plasma renin activity (PRA) (1). Ideally, the patient should not take any medications that affect the renin-angiotensin system (eg, thiazide diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers [ARBs], beta-blockers) for 4 to 6 weeks before tests are done. Plasma renin activity is usually measured in the morning with the patient recumbent. Patients with primary aldosteronism typically have plasma aldosterone > 15 ng/dL (> 0.42 nmol/L) and low levels of PRA, with a ratio of plasma aldosterone (in ng/dL) to plasma renin activity (in ng/mL/hour) > 20. However, the diagnostic ratio depends on the type of assay and assay units and should therefore be individualized. After initial measurements are made, a 4-hour saline infusion or 3 days of dietary salt loading is given, and aldosterone is measured again to see whether it can be suppressed. In primary hyperaldosteronism, serum aldosterone production is autonomous and will not fall below a diagnostic value.
Low levels of both plasma renin activity and aldosterone suggest nonaldosterone mineralocorticoid excess (eg, due to licorice ingestion, Cushing syndrome, or Liddle syndrome). High levels of both plasma renin activity and aldosterone suggest secondary hyperaldosteronism. The principal differences between primary and secondary aldosteronism are shown in the table . In children, Bartter syndrome is distinguished from primary hyperaldosteronism by the absence of hypertension and marked elevation of PRA; there is a similar, milder syndrome in adults with Gitelman syndrome.
Distinguishing Primary and Secondary Aldosteronism
Clinical Finding | Primary Aldosteronism | Secondary Aldosteronism | ||
|---|---|---|---|---|
Adenoma | Hyperplasia | Renovascular or Accelerated Hypertension | Edematous Disorders† | |
Blood pressure | ↑↑ | ↑ | ↑↑↑↑ | N or ↑ |
Edema | Rare | Rare | Rare | Present |
Serum sodium | N or ↑ | N or ↑ | N or ↓ | N or ↓ |
Serum potassium | N or ↓ | N or ↓ | ↓ | N or ↓ |
Plasma renin activity* | ↓↓ | ↓↓ | ↑↑ | ↑ |
Aldosterone | ↑ | ↑ | ↑↑ | ↑ |
* When corrected for age; | ||||
† Secondary to decreased renal blood flow as in heart failure, cirrhosis, nephrotic syndrome. | ||||
↑↑↑↑= very greatly increased; ↑↑= greatly increased; ↑= increased; ↓↓= greatly decreased; ↓= decreased; N = normal. | ||||
Patients with findings suggesting primary hyperaldosteronism should undergo CT or MRI to determine whether the cause is a tumor or hyperplasia. However, imaging tests are relatively insensitive, and most patients require bilateral catheterization of the adrenal veins to measure cortisol and aldosterone levels to confirm whether the aldosterone excess is unilateral (tumor) or bilateral (hyperplasia). It is possible that PET-radionuclide imaging with radiolabeled metomidate or other radionuclides may be more helpful, and increasingly is replacing adrenal vein sampling.
Diagnosis reference
1. Adler GK, Stowasser M, Correa RR, et al. Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2025;110(9):2453-2495. doi:10.1210/clinem/dgaf284
Treatment of Primary Aldosteronism
Surgical removal of tumors
Spironolactone or eplerenone for hyperplasiaSpironolactone or eplerenone for hyperplasia
Tumors should be removed laparoscopically. After removal of an adenoma, serum potassium normalizes and blood pressure decreases in all patients; complete normalization of the blood pressure without the need for antihypertensive treatment occurs in 50 to 70% of patients (1).
Among patients with adrenal hyperplasia, 70% remain hypertensive after bilateral adrenalectomy; thus, surgery is not recommended. Hyperaldosteronism in these patients can usually be controlled by a selective aldosterone blocker such as spironolactone, starting with 50 mg orally once a day and increasing over 1 to 3 months to a maintenance dose, usually around 50 to 100 mg once a day; or by amiloride 5 to 10 mg orally once a day; or another potassium-sparing diuretic. The more specific medication eplerenone 50 mg orally once a day to 200 mg orally twice a day may be used because, unlike Among patients with adrenal hyperplasia, 70% remain hypertensive after bilateral adrenalectomy; thus, surgery is not recommended. Hyperaldosteronism in these patients can usually be controlled by a selective aldosterone blocker such as spironolactone, starting with 50 mg orally once a day and increasing over 1 to 3 months to a maintenance dose, usually around 50 to 100 mg once a day; or by amiloride 5 to 10 mg orally once a day; or another potassium-sparing diuretic. The more specific medication eplerenone 50 mg orally once a day to 200 mg orally twice a day may be used because, unlikespironolactone, it does not block the androgen receptor (which can cause gynecomastia and sexual dysfunction); it is the drug of choice for long-term treatment in males unless low-dose spironolactone is effective.
Approximately half of patients with hyperplasia need additional antihypertensive treatment.
Treatment reference
1. Ekman N, Grossman AB, Dworakowska D. What We Know about and What Is New in Primary Aldosteronism. Int J Mol Sci. 2024;25(2):900. doi:10.3390/ijms25020900
Key Points
Diagnosis should be suspected in hypertensive patients with hypokalemia in the absence of Cushing syndrome.
Initial testing includes measurement of plasma aldosterone levels and plasma renin activity before and after saline infusion or salt loading.
Adrenal imaging tests are done, but often bilateral adrenal vein catheterization is needed to distinguish tumor from hyperplasia.
Tumors are removed, and patients with adrenal hyperplasia are treated with aldosterone blockers such as spironolactone or eplerenone.Tumors are removed, and patients with adrenal hyperplasia are treated with aldosterone blockers such as spironolactone or eplerenone.
