Conn Syndrome

What is Conn Syndrome?

The term Conn syndrome describes the autonomous secretion of aldosterone from the adrenal cortex, a condition also known as primary hyperaldosteronism. This excess hormone causes the kidneys to retain sodium and excrete potassium, leading to hypertension (high blood pressure) and the suppression of renin. It accounts for approximately 5% to 10% of all hypertension cases and represents an even larger share of individuals with resistant hypertension.

Clinicians sometimes refer to this entity as Conn disease to honor the historical description provided by Dr. Jerome Conn. Early detection is critical because even mild cases significantly increase cardiovascular risk. Fortunately, many of the damaging effects can be reversed with targeted medical or surgical therapy.

What causes Conn Syndrome?

Active Conn syndrome typically arises from either a unilateral (one-sided) aldosterone-producing adenoma or bilateral (on both sides) adrenal hyperplasia. In these cases, the zona glomerulosa—the outer layer of the adrenal cortex—becomes overactive. Excess aldosterone increases sodium reabsorption through epithelial sodium channels (ENaC), enhances potassium secretion in the distal nephron, and suppresses renin through volume expansion.

Some cases are associated with genetic forms of primary aldosteronism (familial hyperaldosteronism), although most occur sporadically. Chronic exposure to excess aldosterone also promotes vascular inflammation and myocardial fibrosis (scarring of the heart muscle). These tissue changes often occur before blood pressure becomes severely elevated, allowing for earlier suspicion based on laboratory findings.

What are the signs and symptoms of Conn Syndrome?

Symptoms usually begin with new-onset or resistant hypertension, which may cause persistent headaches. Over time, chronic sodium retention expands intravascular volume, contributing to persistent hypertension. Many individuals also experience muscle weakness and cramps due to the neuromuscular irritability caused by a potassium deficit.

The symptoms of Conn syndrome often emerge gradually. In some cases, intermittent paralysis or polyuria (excessive urination) reveals a chronic lack of potassium. Clinicians watch for symptoms of elevated aldosterone, such as suppressed renin activity despite significant fluctuations in blood pressure. In clinical practice, Conn syndrome symptoms become unmistakable when severe hypertension coincides with refractory hypokalemia (low potassium) and metabolic alkalosis.

How is Conn Syndrome diagnosed?

Initial evaluation involves measuring the plasma aldosterone-to-renin ratio (ARR). To ensure accuracy, this test is performed after temporarily holding medications that might interfere with the results. An elevated ARR with inappropriately high aldosterone and suppressed renin suggests primary aldosteronism and requires confirmatory testing.

If the biochemical tests confirm the diagnosis, a CT or MRI of the adrenal glands is used to localize potential nodules. However, because some nodules are non-functional, adrenal venous sampling is often required to distinguish true lateralized aldosterone secretion from bilateral disease. Renal artery imaging may also be performed if renovascular hypertension is considered a competing diagnosis.

How is Conn Syndrome treated?

Unilateral adenomas are typically treated with laparoscopic adrenalectomy (surgical removal of the adrenal gland). This procedure cures or significantly improves hypertension in many patients. In contrast, individuals with bilateral hyperplasia rely on mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, to block the effects of the excess aldosterone.

Dietary sodium restriction and potassium supplementation are essential to support biochemical balance while awaiting definitive therapy. Following treatment, clinicians closely monitor serum potassium, aldosterone, and renin levels to document resolution. If hypertension remains resistant despite normalized electrolytes, further imaging or genetic testing for familial hyperaldosteronism may be necessary.

What are the most important facts to know about Conn Syndrome?

• Conn syndrome, or Conn disease, is a form of primary hyperaldosteronism that causes 5–10% of all hypertension cases.
• The condition is driven by autonomous aldosterone secretion from an adrenal adenoma or hyperplasia, leading to sodium retention and renin suppression.
• Refractory hypertension is the hallmark of Conn syndrome and hyperaldosteronism.
• Key clinical clues include hypokalemia, muscle weakness, and suppressed renin levels.
• The aldosterone-to-renin ratio is the primary screening tool, followed by confirmatory suppression tests and adrenal venous sampling.
• Treatment involves laparoscopic surgery for unilateral cases or mineralocorticoid receptor antagonists for bilateral disease.