The syndrome of apparent mineralocorticoid excess (AME) is a rare genetic disorder characterized by a disturbance in how the body processes certain steroid hormones. This condition leads to symptoms that mimic an overproduction of mineralocorticoids, a group of hormones that regulate salt and water balance. However, in AME, the actual levels of these specific hormones, like aldosterone, are not elevated. Instead, the body’s normal hormonal balance is disrupted, causing issues primarily with blood pressure regulation and electrolyte levels.
Understanding Apparent Mineralocorticoid Excess
The “apparent” nature of this syndrome stems from a malfunction in a specific enzyme called 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme, found mainly in mineralocorticoid target tissues like the kidneys, normally converts active cortisol into inactive cortisone. This conversion is important because mineralocorticoid receptors, which regulate sodium and potassium, cannot distinguish between cortisol and aldosterone.
Since cortisol circulates in the body at levels 100 to 1000 times higher than aldosterone, the 11β-HSD2 enzyme acts as a protective mechanism. When the 11β-HSD2 enzyme is deficient or impaired, cortisol is not properly inactivated, allowing abundant cortisol to bind to mineralocorticoid receptors. This leads to excessive receptor activation and effects similar to having too much aldosterone, even with low or normal aldosterone levels.
Recognizing the Signs
AME often presents with distinct physiological changes. A common symptom is severe high blood pressure, which can manifest early in life. This hypertension often proves resistant to standard treatments.
Another feature is hypokalemia, or abnormally low potassium levels in the blood, which can lead to muscle weakness and fatigue. Excessive urination and increased thirst are also common. These symptoms arise because the overstimulated mineralocorticoid receptors in the kidneys cause the body to retain too much sodium and water, while simultaneously losing excessive amounts of potassium, disrupting the body’s electrolyte balance.
How it Develops
Apparent mineralocorticoid excess is an autosomal recessive genetic disorder. This means a child must inherit two copies of a mutated gene, one from each parent, to develop the condition. The specific gene involved is HSD11B2, which provides instructions for making the 11β-HSD2 enzyme.
Parents who carry one copy of the mutated HSD11B2 gene typically do not show any signs or symptoms of the disorder themselves. Over 50 mutations in the HSD11B2 gene have been identified worldwide, leading to varying degrees of enzyme dysfunction. The syndrome is considered rare, with fewer than 100 cases reported in medical literature.
Diagnosis and Treatment Approaches
Diagnosing apparent mineralocorticoid excess involves a combination of biochemical and genetic tests. Blood tests typically reveal low levels of renin and aldosterone, hormones typically elevated in true mineralocorticoid excess. Additionally, potassium levels are usually low.
A diagnostic indicator is an elevated ratio of cortisol metabolites to cortisone metabolites in urine, often 10 to 100 times higher than normal, reflecting impaired 11β-HSD2 activity. Genetic testing for mutations in the HSD11B2 gene confirms the diagnosis.
Treatment strategies aim to counteract the effects of excess cortisol on mineralocorticoid receptors and manage symptoms. Mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, are commonly prescribed to block the action of cortisol at these receptors. In some cases, low-dose corticosteroids like dexamethasone may be used to suppress ACTH production, reducing the body’s own cortisol production.
Managing blood pressure and correcting potassium imbalances are also aspects of treatment. This may involve a low-sodium diet and potassium supplementation. Early and accurate diagnosis, followed by appropriate treatment, helps prevent long-term complications such as kidney damage, heart problems, and neurological issues.