Conn’s Syndrome, also known as Primary Hyperaldosteronism, is an endocrine disorder defined by the excessive production of the hormone aldosterone by the adrenal glands. This hormonal overactivity leads to high blood pressure, which is often resistant to standard medications. Conn’s Syndrome is generally classified as a structural or functional disorder of the adrenal glands, not an autoimmune disease.
What Exactly Is Conn’s Syndrome?
Conn’s Syndrome is a form of secondary hypertension, meaning the high blood pressure has an identifiable underlying cause. The adrenal glands, which sit atop the kidneys, produce aldosterone, a steroid hormone that manages the balance of sodium and potassium in the blood. Aldosterone achieves this by causing the kidneys to retain sodium and water while excreting potassium.
Excessive aldosterone production forces the body to hold onto too much salt and fluid, significantly increasing blood volume and pressure. The over-excretion of potassium can also lead to low potassium levels, known as hypokalemia. The excess aldosterone places patients at a heightened risk for serious cardiovascular events like stroke, heart attack, and kidney failure.
The standard form of Conn’s Syndrome is not an autoimmune condition, but rather a disorder of hormonal overproduction. This distinction is based on the mechanism of the disease, which involves tissue overgrowth or tumor formation instead of immune system attack.
The Established Causes of Conn’s Syndrome
The reasons for aldosterone overproduction are categorized into two main, non-autoimmune types.
Aldosterone-Producing Adenoma (APA)
The first is an Aldosterone-Producing Adenoma (APA), often called a Conn’s Tumor, which accounts for about 30% to 40% of cases. This is a small, benign (non-cancerous) tumor that forms in the outer layer of one adrenal gland. This tumor independently produces large amounts of aldosterone, regardless of the body’s needs.
Bilateral Idiopathic Adrenal Hyperplasia (BIAH)
The second primary cause is Bilateral Idiopathic Adrenal Hyperplasia (BIAH), also referred to as idiopathic hyperaldosteronism, which is responsible for the majority of cases, ranging from 60% to 70%. In BIAH, both adrenal glands become overactive due to the overgrowth of tissue. The specific trigger for this bilateral overgrowth is not fully understood, but it is considered a functional disorder of the glands.
In both APA and BIAH, the issue is an autonomous or over-responsive production of the hormone. This is a functional problem of the tissue, where cells are producing too much of a substance. The immune system is not involved in attacking or damaging the adrenal tissue to cause this excess production.
Autoimmunity in Endocrine Disease: Making the Distinction
An autoimmune disease occurs when the body’s immune system mistakenly produces antibodies that attack healthy tissues, causing inflammation and damage. In the endocrine system, this mechanism is seen in conditions like Type 1 Diabetes, where the immune system destroys insulin-producing cells in the pancreas. Autoimmune adrenal disease also exists, but it typically presents as Addison’s Disease.
Addison’s Disease involves autoantibodies attacking the adrenal cortex, which results in the underproduction of hormones, including aldosterone and cortisol. This leads to adrenal insufficiency, which is the opposite effect of Conn’s Syndrome. The difference lies in the outcome: autoimmunity usually causes destruction and hormone deficiency, while Conn’s Syndrome is characterized by overproduction due to growth or overactivity.
Research has explored a possible connection, noting that patients with Conn’s Syndrome may have an increased risk for developing other, distinct autoimmune diseases. However, this association does not classify Conn’s Syndrome itself as an autoimmune condition.
How Conn’s Syndrome Is Diagnosed and Managed
Diagnosis begins with screening blood tests, specifically measuring the ratio of plasma aldosterone to plasma renin activity (ARR). Renin normally stimulates aldosterone release, but in Conn’s Syndrome, high aldosterone suppresses renin, leading to a high ARR. Confirmatory tests, such as salt loading tests, verify that aldosterone production is independent of the body’s control.
Once confirmed, imaging like a computed tomography (CT) scan is used to look for an adenoma on one adrenal gland. The definitive step to determine if the disease is unilateral (one gland) or bilateral (both glands) is Adrenal Vein Sampling (AVS). AVS measures the aldosterone concentration directly from the veins draining each adrenal gland.
The management strategy depends on the cause identified.
Surgical Management
For patients with a single Aldosterone-Producing Adenoma (APA), the preferred treatment is a laparoscopic adrenalectomy (surgical removal of the affected gland). This procedure can resolve low potassium levels and significantly improve hypertension in many patients.
Medical Management
For individuals with Bilateral Idiopathic Adrenal Hyperplasia (BIAH) or those unable to undergo surgery, treatment involves medication. Mineralocorticoid Receptor Antagonists (MRAs), such as spironolactone or eplerenone, are prescribed to block the effect of excess aldosterone on the body. This medical management is a lifelong commitment aimed at controlling blood pressure and normalizing potassium levels.