Hyperaldosteronism and Hypoaldosteronism

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Aldosterone is a mineralocorticoid hormone produced by the adrenal cortex that plays a central role in regulating blood pressure, sodium balance, and potassium levels. Disorders of aldosterone production fall into two major categories: hyperaldosteronism (excess aldosterone) and hypoaldosteronism (deficient aldosterone or resistance to its effects). Both conditions significantly affect cardiovascular and cardiovascular health.

Hyperaldosteronism (Aldosteronism)

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https://www.researchgate.net/publication/6140951/figure/fig1/AS%3A277878391492612%401443262779445/Schematic-of-aldosterone-physiology-In-renal-insufficiency-aldosterone-secretion-seems.png

Hyperaldosteronism is a condition in which the adrenal glands produce excessive aldosterone. This hormone increases sodium and water retention while promoting potassium excretion. As a result, patients typically develop:

  • Hypertension (often treatment-resistant)

  • Hypokalemia (low potassium)

  • Metabolic alkalosis

  • Sodium retention and volume expansion

Hyperaldosteronism is divided into primary and secondary forms.

Primary Aldosteronism (Conn's Syndrome)

Primary aldosteronism results from a defect within the adrenal glands themselves. It is often suspected in patients with resistant hypertension or unexplained low potassium levels.

Common causes include: 
Adrenal adenoma (Conn's syndrome): A benign tumor in one adrenal gland producing excess aldosterone.

  • Bilateral adrenal hyperplasia: Overactivity and enlargement of both glands.

  • Adrenal carcinoma: A rare malignant tumor.

  • Familial hyperaldosteronism: Inherited genetic mutations affecting aldosterone regulation.

Secondary Aldosteronism

Secondary aldosteronism occurs when external factors stimulate excess aldosterone production via activation of the renin-angiotensin-aldosterone system (RAAS).

Common causes include:

  • Renal artery stenosis: Reduced blood flow to the kidneys stimulates renin release.

  • Congestive heart failure: Decreased effective circulation activates RAAS.

  • Liver cirrhosis with ascites: Fluid shifts and low effective blood volume stimulate renin.

  • Renin-secreting tumors: Rare tumors that drive excessive renin production.

In secondary aldosteronism, aldosterone elevation is an appropriate but exaggerated physiological response to reduced effective blood flow.

Treatment of Hyperaldosteronism

Management depends on whether the condition is unilateral (one gland) or bilateral (both glands).

Unilateral Disease

  • Unilateral adrenalectomy: Surgical removal of the affected adrenal gland is the preferred treatment for aldosterone-producing adenomas.

  • Surgery can potentially cure hypertension and correct hypokalemia.

Bilateral Disease

  • Medical management is the standard approach.

Key medications include:

  • Spironolactone (Aldactone): First-line mineralocorticoid receptor antagonist (MRA); lowers blood pressure and corrects potassium imbalance.

  • Eplerenone (Inspra): A more selective MRA with fewer hormonal side effects such as gynecomastia.

  • Amiloride: An alternative potassium-sparing agent if MRAs are not tolerated.

Additional Management Strategies

  • Dietary sodium restriction

  • Regular monitoring of blood pressure

  • Monitoring potassium and kidney function (creatinine levels)

  • Dose adjustments based on laboratory findings

For secondary aldosteronism, treatment primarily focuses on correcting the underlying cause, such as improving heart failure management or restoring renal blood flow.

Hypoaldosteronism

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Hypoaldosteronism is characterized by insufficient aldosterone production or resistance to its effects. This results in:

  • Hyperkalemia (high potassium)

  • Hyponatremia (low sodium)

  • Hypotension

  • Metabolic acidosis

  • Reduced circulating blood volume (hypovolemia)

Primary Causes of Hypoaldosteronism

Hyporeninemic Hypoaldosteronism (Most Common Acquired Form)

  • Characterized by low renin production

  • Common in diabetic nephropathy and chronic kidney disease

  • Frequently seen in elderly patients

    -------------------------------------------------------------------------------- 

Medication-Induced 

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Certain medications interfere with aldosterone production or action:

  • ACE inhibitors

  • Angiotensin receptor blockers (ARBs)

  • Nonsteroidal anti-inflammatory drugs (NSAIDs)

  • Heparin

  • Calcineurin inhibitors

    -------------------------------------------------------------------------------- 

Primary Adrenal Insufficiency (Addison's Disease)

Damage to the adrenal cortex leads to reduced aldosterone synthesis. Causes include:

  • Autoimmune destruction

  • Tuberculosis

  • HIV infection

  • Adrenal hemorrhage

Congenital Adrenal Hyperplasia (CAH)

Inherited enzyme deficiencies, most commonly 21-hydroxylase deficiency, impair aldosterone production.

Pseudohypoaldosteronism

Aldosterone levels are normal or elevated, but target organs (primarily the kidneys) are resistant to its effects.

Congenital Isolated Hypoaldosteronism

Rare genetic mutations, most commonly aldosterone synthase (CYP11B2) deficiency, impair aldosterone production.

Risk Factors for Hypoaldosteronism

  • Diabetes mellitus with chronic kidney disease

  • Advanced age with polypharmacy

  • Autoimmune disorders

  • Chronic interstitial renal disease

Treatment of Hypoaldosteronism

Treatment depends on the underlying cause and severity.

  • Discontinue or adjust causative medications

  • Mineralocorticoid replacement (fludrocortisone) when appropriate

  • Manage hyperkalemia with dietary potassium restriction or potassium-binding agents

  • Treat underlying adrenal insufficiency with glucocorticoid replacement

  • Optimize management of chronic kidney disease

Regular monitoring of potassium levels and kidney function is essential to prevent life-threatening complications such as cardiac arrhythmias.

Summary

Hyperaldosteronism and hypoaldosteronism represent opposite ends of aldosterone imbalance but both significantly affect blood pressure and electrolyte homeostasis.

Hyperaldosteronism leads to hypertension and hypokalemia and may be surgically curable in unilateral cases or medically managed in bilateral disease.

Hypoaldosteronism leads to hyperkalemia and hypotension and commonly occurs in patients with chronic kidney disease, diabetes, adrenal insufficiency, or medication effects.

Early recognition, appropriate diagnostic evaluation, and targeted treatment are essential to prevent long-term cardiovascular and renal complications.

 

References:

HYPORENINAEMIC HYPOALDOSTERONISM (HH) AS THE CAUSE OF UNEXPLAINED HYPERKALAEMIA  https://asean-endocrinejournal.org/index.php/JAFES/article/view/5293

Hypoaldosteronism https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/hypoaldosteronism

Hyporeninemic Hypoaldosteronism https://emedicine.medscape.com/article/242494-overview

Hypoaldosteronism https://www.ncbi.nlm.nih.gov/sites/books/NBK555992/

Hyperaldosteronism | Clinical Medicine https://www.youtube.com/watch?v=_3El2bP9HJ8&t=45s

Hyperaldosteronism: https://www.ncbi.nlm.nih.gov/books/NBK499983/

Diagnosis and treatment of primary aldosteronism: https://www.sciencedirect.com/science/article/abs/pii/S2213858721002102

Hyperaldosteronism https://my.clevelandclinic.org/health/diseases/16448-hyperaldosteronism

© 2000-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9   

 

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