Apparent mineralocorticoid excess syndrome

Overview

Apparent Mineralocorticoid Excess Syndrome (AME) is a rare autosomal recessive genetic disorder characterized by hypertension, hypokalemia, metabolic alkalosis, and low levels of plasma renin and aldosterone. Despite these findings, the kidneys respond as if there is an excess of mineralocorticoids (like aldosterone), even though actual levels are low—hence the term “apparent” mineralocorticoid excess.

The condition results from impaired inactivation of cortisol in the kidney, leading to excessive stimulation of mineralocorticoid receptors, which disrupts salt and water balance and causes early-onset high blood pressure and related complications.

Causes

AME is caused by mutations in the HSD11B2 gene, which encodes the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme converts active cortisol into inactive cortisone in the renal tubules. When this enzyme is deficient or nonfunctional, cortisol accumulates and abnormally activates mineralocorticoid receptors.

There is also an acquired form of AME due to substances that inhibit 11β-HSD2, such as excessive intake of licorice (which contains glycyrrhetinic acid).

Symptoms

Symptoms usually begin in infancy or early childhood and may vary in severity. Common features include:

• Severe hypertension (often resistant to treatment)

• Hypokalemia: Low potassium levels, causing fatigue, muscle weakness, or cramps

• Metabolic alkalosis: High blood pH due to excessive bicarbonate

• Growth retardation: Short stature and poor weight gain

• Polyuria and polydipsia: Excessive urination and thirst

• Low plasma renin and aldosterone levels despite symptoms suggesting mineralocorticoid excess

Diagnosis

Diagnosis of AME is based on a combination of clinical, biochemical, and genetic findings:

• Blood tests: Show hypokalemia, metabolic alkalosis, low renin, and low aldosterone

• Urine steroid analysis: Elevated ratio of cortisol to cortisone metabolites (e.g., tetrahydrocortisol/tetrahydrocortisone)

• Genetic testing: Confirms mutations in the HSD11B2 gene

• Family history: Often positive for consanguinity or similar presentations in siblings

Acquired causes, such as chronic licorice ingestion, should also be ruled out.

Treatment

Treatment aims to control blood pressure, correct electrolyte imbalances, and reduce mineralocorticoid receptor activation:

Pharmacologic Therapy:

• Mineralocorticoid receptor antagonists: Such as spironolactone or eplerenone

• Potassium-sparing diuretics: Such as amiloride

• Salt-restricted diet: To manage blood pressure and reduce sodium retention

• Glucocorticoid therapy: In some cases (e.g., dexamethasone) to suppress endogenous cortisol production via negative feedback

Supportive Care:

• Regular monitoring of blood pressure, potassium levels, and renal function

• Growth and developmental assessments in children

• Genetic counseling for affected families

Prognosis

With early diagnosis and appropriate treatment, the prognosis for AME can be significantly improved. Untreated, the syndrome can lead to:

• Severe and early-onset hypertension-related complications (e.g., stroke, heart failure)

• Renal damage and chronic kidney disease

• Failure to thrive and growth retardation in children

Lifelong treatment and follow-up are usually required. When managed properly, many patients can achieve good blood pressure control and normal growth and development.