Primary hyperaldosteronism is a condition caused by the overproduction of aldosterone, a hormone from the adrenal glands. Aldosterone’s role is to regulate blood pressure by managing sodium and potassium. When produced in excess, it leads to sodium retention and potassium loss, causing elevated blood pressure. The term “primary” indicates the issue originates within the adrenal glands themselves. This distinction separates the condition from problems arising elsewhere that might affect adrenal function.
Adrenal Gland Growths
One of the most frequent causes of primary hyperaldosteronism is a benign (non-cancerous) growth on one of the adrenal glands. These growths, known as aldosterone-producing adenomas (APAs), function independently of the body’s normal regulatory systems. An adenoma on a single gland autonomously secretes large volumes of aldosterone. These tumors are also referred to as Conn’s adenomas and are a leading cause of this type of hypertension.
A much rarer cause is an adrenocortical carcinoma, which is a malignant (cancerous) tumor. Although it accounts for a very small fraction of cases, differentiating it from a benign growth is necessary to determine the appropriate treatment and management.
These growths disrupt the normal feedback loops that control aldosterone release. The body can no longer suppress hormone production in response to high blood pressure, as the tumor operates outside this system. This unchecked secretion sustains the elevated blood pressure and low potassium levels. Diagnosis frequently involves imaging tests, like a CT scan, to identify a tumor on the adrenal glands.
Bilateral Adrenal Overactivity
Another cause of primary hyperaldosteronism is the overactivity of both adrenal glands, a condition called bilateral adrenal hyperplasia (BAH). In BAH, the glands become enlarged or overactive, releasing too much aldosterone. This condition is also called idiopathic hyperaldosteronism, as the trigger is often unknown, and it accounts for up to 70% of diagnoses.
Unlike an adenoma on a single gland, BAH involves a generalized dysfunction affecting both glands. This distinction is meaningful because the management approach differs significantly. While a single tumor may be surgically removed, addressing overactivity in both glands often requires medication to block the hormone’s effects.
A less common variant is unilateral adrenal hyperplasia, where only one adrenal gland is enlarged and hyperactive. The diagnostic process, which may include adrenal vein sampling, helps to pinpoint whether one or both glands are the source of the overproduction, guiding subsequent decisions.
Genetic Predisposition
In some instances, primary hyperaldosteronism is inherited, a category known as Familial Hyperaldosteronism (FH). These rare forms are caused by specific gene mutations passed down through families. Identifying a hereditary basis is important for screening family members who may be at risk.
Different types of FH are linked to a specific genetic anomaly. Familial Hyperaldosteronism Type I, also called Glucocorticoid-Remediable Aldosteronism, results from the fusion of two genes, CYP11B1 and CYP11B2. This genetic arrangement causes aldosterone production to be regulated by a different hormone.
Other inherited forms present clinical pictures similar to more common causes but have a distinct genetic link. Familial Hyperaldosteronism Type II can manifest as an adrenal adenoma or bilateral hyperplasia but is defined by its occurrence in multiple family members. A more severe version, Type III, is caused by mutations in the KCNJ5 gene, while Type IV is associated with mutations in the CACNA1D gene.
Distinguishing from Secondary Hyperaldosteronism
It is necessary to differentiate primary hyperaldosteronism from secondary hyperaldosteronism. In the secondary form, the adrenal glands are not the source of the problem. Instead, they are functioning correctly but are overstimulated by signals from outside the glands, causing them to produce excess aldosterone in response to an external trigger.
This external signaling is often caused by a reduction in blood flow to the kidneys, a condition known as renal artery stenosis. When the kidneys sense decreased blood flow, they release an enzyme called renin, which initiates a hormonal cascade that tells the adrenal glands to produce more aldosterone. This is the body’s attempt to raise blood pressure and restore flow to the kidneys. Other conditions like heart failure or liver cirrhosis can also cause this secondary form.
The distinction is determined through blood tests that measure levels of both aldosterone and renin. In primary hyperaldosteronism, renin levels are low because high blood pressure signals the kidneys to stop producing it. In contrast, in the secondary form, renin levels are high, reflecting the underlying issue stimulating the system. This distinction is important because treatment for secondary hyperaldosteronism focuses on resolving the external issue, not the adrenal glands.