Pseudoaldosteronism is a medical condition that mimics the effects of excess aldosterone, a hormone that regulates the body’s sodium and potassium balance. Patients present with high blood pressure and low blood potassium, but the defining feature is that lab tests show normal or low aldosterone levels. This indicates that while the body behaves as if it has too much aldosterone, the hormone itself is not the cause, pointing to other underlying issues.
Underlying Causes of Pseudoaldosteronism
The causes of pseudoaldosteronism fall into acquired and genetic categories. Acquired forms are linked to external substances, most notably glycyrrhizic acid, found in black licorice, some herbal teas, and certain chewing tobaccos. This compound interferes with a protective mechanism in the kidneys.
Glycyrrhizic acid inhibits an enzyme called 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme normally converts active cortisol to inactive cortisone within the kidneys. When 11β-HSD2 is blocked, high levels of cortisol activate mineralocorticoid receptors meant for aldosterone, leading to symptoms of aldosterone excess.
Genetic causes produce a similar result through inherited defects. Liddle syndrome is an autosomal dominant disorder affecting the kidneys’ epithelial sodium channels (ENaC). A mutation impairs the breakdown of these channels, increasing their numbers and causing abnormally high reabsorption of sodium and water.
Another genetic cause is Apparent Mineralocorticoid Excess (AME), an autosomal recessive disorder. In AME, mutations in the HSD11B2 gene cause a deficiency of the 11β-HSD2 enzyme. This allows cortisol to inappropriately stimulate mineralocorticoid receptors, mirroring high aldosterone levels from birth.
Clinical Presentation and Symptoms
The most prominent signs of pseudoaldosteronism are treatment-resistant hypertension and low blood potassium (hypokalemia). The underlying mechanisms cause the kidneys to retain excess sodium and water. This fluid volume expansion leads to elevated blood pressure that is often difficult to control with standard medications.
As the kidneys retain sodium, they excrete too much potassium into the urine. This loss of potassium is responsible for many secondary symptoms, as potassium is needed for the proper electrical function of muscle and nerve cells. Common symptoms include:
- Muscle weakness or fatigue
- Painful muscle cramps or spasms
- Metabolic alkalosis, a condition where the blood becomes too alkaline
- Excessive urination (polyuria) and increased thirst (polydipsia)
The Diagnostic Process
Diagnosing pseudoaldosteronism begins when a patient presents with high blood pressure and hypokalemia. Initial lab work confirms these findings and prompts an investigation of the renin-angiotensin-aldosterone system, which regulates blood pressure and electrolyte balance.
The primary step in diagnosis is measuring plasma renin activity and aldosterone concentration. In pseudoaldosteronism, the defining result is the combination of low plasma renin and low aldosterone levels. This paradoxical finding indicates the body is suppressing both, despite symptoms of mineralocorticoid excess, distinguishing it from true hyperaldosteronism where levels would be high.
Once low-renin, low-aldosterone hypertension is established, the focus shifts to finding the cause. A detailed patient history will include questions about consuming black licorice or other products with glycyrrhizic acid. If an acquired cause is suspected, removing the substance and observing for improvement can be both diagnostic and therapeutic.
To confirm a genetic cause, specialized tests are used. A 24-hour urine collection can measure the ratio of urinary free cortisol to cortisone; an elevated ratio points toward AME. For suspected Liddle syndrome, genetic testing can identify mutations in the genes for the epithelial sodium channel.
Management and Treatment Strategies
Treatment for pseudoaldosteronism is tailored to its specific underlying cause. For acquired cases, such as those induced by licorice, the primary intervention is the complete removal of the offending substance from the diet.
When the cause is genetic, management relies on targeted medications. In Liddle syndrome, treatment involves potassium-sparing diuretics like amiloride or triamterene. These drugs directly block the overactive epithelial sodium channels (ENaC), which reduces sodium reabsorption, lowers blood pressure, and corrects low potassium levels.
For patients with Apparent Mineralocorticoid Excess (AME), the treatment involves low doses of a synthetic glucocorticoid like dexamethasone. This suppresses the body’s own cortisol production. By reducing circulating cortisol, less is available to mistakenly activate mineralocorticoid receptors in the kidney.
In addition to these specific treatments, a low-sodium diet is recommended for all individuals with pseudoaldosteronism. This dietary change helps manage hypertension by alleviating the body’s tendency to retain fluid and complements the effects of medication.