Primary Aldosteronism: A Key Endocrine Driver of Resistant Hypertension

By SWA

A clinical scenario involving hydrocortisone (20 mg) therapy, a urine pH of 6.5, and elevated blood pressure at 170 mmHg may signal an underlying endocrine etiology—most notably primary aldosteronism (PA). This frequently underdiagnosed condition is a significant contributor to secondary hypertension and has critical implications for long-term cardiovascular and renal outcomes.

Physiology of Aldosterone

Aldosterone, a mineralocorticoid synthesized in the zona glomerulosa of the adrenal cortex, acts on the distal nephron to enhance sodium reabsorption and potassium excretion. Through its regulation of extracellular fluid volume, aldosterone directly modulates systemic blood pressure.

Pathophysiology of Primary Aldosteronism

Primary aldosteronism is characterized by autonomous aldosterone production—independent of renin-angiotensin signaling—typically caused by:

  • Aldosterone-producing adenoma (APA)

  • Bilateral adrenal hyperplasia (BAH)

  • Less commonly, adrenocortical carcinoma or familial hyperaldosteronism

This dysregulated aldosterone secretion leads to volume expansion, hypertension, hypokalemia, and in some cases, metabolic alkalosis.

Clinical Manifestations and Laboratory Findings

Common clinical features include:

  • Resistant hypertension (often diastolic dominant)

  • Spontaneous or diuretic-induced hypokalemia

  • Muscle cramps, fatigue, or arrhythmias in severe hypokalemia

  • Mild metabolic alkalosis, sometimes reflected in urine pH alterations

In this context, a urine pH of 6.5 may reflect renal compensation for chronic electrolyte imbalance.

Diagnostic Workup

Initial Screening:

  • Plasma aldosterone concentration (PAC)

  • Plasma renin activity (PRA) or direct renin concentration (DRC)

  • Aldosterone-to-renin ratio (ARR): An elevated ratio is a sensitive screening tool

Confirmatory Testing:

  • Oral sodium loading test

  • Saline infusion test

  • Fludrocortisone suppression test

  • Captopril challenge test

Imaging:

  • Adrenal CT scan is used to identify anatomical lesions

  • Adrenal venous sampling (AVS) remains the gold standard to differentiate unilateral from bilateral disease prior to surgical intervention

Management Strategies

Surgical Intervention:

  • Unilateral adrenalectomy is preferred in cases of APA, with potential for complete hypertension resolution in up to 50% of patients

Medical Management:

  • For bilateral hyperplasia or non-surgical candidates:

    • Mineralocorticoid receptor antagonists:

      • Spironolactone (first-line but anti-androgenic side effects common)

      • Eplerenone (more selective, fewer side effects)

    • Adjunct antihypertensives as needed

Clinical Significance

PA is not only a cause of secondary hypertension but also an independent risk factor for cardiovascular morbidity, including left ventricular hypertrophy, atrial fibrillation, and renal dysfunction—even beyond what is explained by blood pressure elevation alone. Early identification and targeted therapy significantly reduce these risks.

Key Takeaways for Clinicians:

  • Consider PA in patients with hypertension and hypokalemia, resistant hypertension, or incidental adrenal masses

  • Use ARR as a frontline screening tool

  • Treat definitively when possible; medical therapy is highly effective in bilateral disease

  • Monitor for electrolyte disturbances and renin suppression during therapy

References

Primary and secondary hyperaldosteronism https://medlineplus.gov/ency/article/000330.htm

  1. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline https://pubmed.ncbi.nlm.nih.gov/26934393/

  2. Appraisal of Modified Tests for Diagnosis and Treatment of Primary Aldosteronism: A Single Center Experience https://esmed.org/MRA/mra/article/view/6161

  3. Primary Aldosteronism: Cardiovascular Outcomes Pre- and Post-treatment
    https://pubmed.ncbi.nlm.nih.gov/31352525/

  4. Johns Hopkins Medicine.
    Primary Aldosteronism (Conn's Syndrome).
    Available at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/primary-aldosteronism

  5. Vaidya A, Mulatero P, Baudrand R, Adler GK.
    The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment.
    Endocr Rev. https://academic.oup.com/edrv/article/39/6/1057/5074252?login=false

     


© 2000-2025 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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