Understanding Apparent Mineralocorticoid Excess

Receiving a diagnosis of Apparent Mineralocorticoid Excess (AME) for you or your child can feel like being handed a map to a place no one has ever heard of. It is natural to feel a sense of isolation or confusion when even your local pediatrician might be reaching for a medical textbook to understand it. Because AME is incredibly rare, you are likely the first person in your community—and perhaps the first in your doctor’s career—to face this challenge ^[1][2].

How Rare is AME?

AME is truly “ultra-rare.” While many rare diseases affect one in a few thousand people, classic AME is estimated to affect only about 0.6 to 6.8 people for every 10 million ^[3]. While historical literature cites fewer than 100 documented cases, it is likely underdiagnosed.

Because it is so uncommon, it is completely normal for a primary care doctor to have never seen a case. Most doctors only encounter AME as a single paragraph in a medical school textbook. This is why your care will likely transition to a specialist, such as a nephrologist (kidney specialist) or an endocrinologist (hormone specialist), who has the specific tools to manage this condition.

What is Happening in the Body?

To understand AME, it helps to think of the kidney as having a “security guard” for its hormone receptors. Usually, a hormone called aldosterone is the only one supposed to turn on the kidney’s “salt-saving” switch. Another hormone, cortisol (your body’s stress hormone), is also capable of turning on this switch, but it is normally blocked from doing so ^[4][5].

The body uses an enzyme called 11β-HSD2 to act as this security guard. It catches cortisol and turns it into an inactive form called cortisone before it can touch the salt-saving switch ^[6][5]. In AME, this security guard is either missing or not working. As a result, the kidney’s receptors are stimulated by cortisol. The kidney “thinks” the body is starving for salt and begins to hold onto sodium and water while dumping potassium ^[7][8]. This leads to the classic signs of AME: severe high blood pressure and low potassium levels.

Genetic (Classic) vs. Acquired AME

There are two ways someone might develop AME: they were born with it (genetic), or they were exposed to something that stopped their “security guard” enzyme from working (acquired).

Classic AME (Genetic)

Classic AME is a genetic condition caused by mutations in the HSD11B2 gene ^[7].

• Inheritance: It follows an autosomal recessive pattern. This means for a person to have the condition, they must inherit one changed gene from each parent ^[9][10].
• Carrier Status: Parents are typically “carriers,” meaning they have one healthy gene and one changed gene. Carriers usually have no symptoms and no high blood pressure ^[7][10].
• Presentation: This form usually appears very early in childhood, often involving poor growth (failure to thrive) and excessive thirst or urination ^[11][12]. Milder forms can sometimes present in adulthood.

Acquired AME

In some cases, a person might have a working gene but something in their environment chemically “turns off” the 11β-HSD2 enzyme.

• Licorice: The most common cause of acquired AME is consuming large amounts of real licorice (specifically glycyrrhizic acid). This substance chemically disables the security guard enzyme, mimicking the genetic disease ^[13][14]. Note that many “licorice” flavored candies in the U.S. use anise oil and do not contain real glycyrrhizic acid.
• Medications: Certain medications, particularly the antifungal drug posaconazole, have been found to inhibit this same enzyme or related pathways, leading to temporary AME-like symptoms ^[15][16]. Important: Never stop a prescribed medication on your own; if you suspect it is causing high blood pressure, consult your prescriber promptly.

Why Diagnosis Takes Time

Because AME is so rare, doctors usually look for more common causes of high blood pressure first. A diagnosis of AME is often suspected only after blood tests show a “low-renin, low-aldosterone” pattern—meaning the body has shut down its normal salt-regulating hormones because it already feels overloaded ^[11][17].

To investigate further, specialists look at the urinary cortisol-to-cortisone metabolite ratio. In a healthy person, there is much more cortisone metabolite than cortisol metabolite in the urine. In AME, the ratio is abnormal because the conversion process is broken ^[18][12]. Genetic testing is then used to find the specific mutation in the HSD11B2 gene to confirm the classic form of the disease ^[9][19].

While the journey to a diagnosis can be overwhelming, identifying the specific type of AME—whether genetic or acquired—is the first step in creating a targeted plan to protect the kidneys and heart.