What Is Conn's Syndrome?

Conn’s syndrome, also known as primary hyperaldosteronism, is a hormonal disorder. It occurs when one or both adrenal glands generate more of the hormone aldosterone than normal. 

The purpose of aldosterone is to balance the levels of salt and potassium in your body to control blood pressure. High aldosterone makes the kidneys filter out potassium while absorbing sodium back into the blood, which leads to high blood pressure (hypertension).¹

This condition is named after Dr. Conn, who first described it in 1955. Conn’s syndrome may be considered a serious disease because of its severe long-term effects. If a patient doesn’t take their medicines, hypertension causes a higher risk of heart failure, heart attacks, strokes, and kidney failure. 

Furthermore, the accompanying low potassium levels (hypokalaemia), can lead to irregular heart rhythms. Hypokalaemia symptoms that are not deadly, but still unpleasant, include fatigue, numbness, muscle weakness, or cramps.² 

Causes of Conn’s syndrome

Conn’s syndrome may be caused by the following factors:

Bilateral adrenal hyperplasia 

Bilateral adrenal hyperplasia, a condition where both adrenal glands become abnormally large, causes around 66% of Conn’s syndrome cases.⁴ 

It typically presents as hypertension that is resistant to the most common blood pressure medications, which include: ACE inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, beta- and alpha-blockers.

Aldosterone-producing adenoma (Conn's disease) 

This is responsible for around 33% of cases.⁴ Do not be deceived by the similar names, as there is a difference between Conn's syndrome and Conn's disease.

Conn's syndrome (primary hyperaldosteronism), as discussed above, is a condition in which the adrenal glands produce too much aldosterone, leading to increased sodium retention and potassium loss in the body. This can cause high blood pressure, muscle weakness, and fatigue, among other symptoms.

On the other hand, Conn's disease refers to a specific form of primary hyperaldosteronism caused by a small, benign (non-cancerous) tumour in the adrenal gland called an aldosterone-producing adenoma (APA). Compared to patients with bilateral adrenal hyperplasia, patients with APAs tend to be younger with more severe hypertension and hypokalaemia.⁵

This means Conn's syndrome can refer to any cause of primary hyperaldosteronism, while Conn's disease specifically refers to the form caused by an APA.

Primary (unilateral) adrenal hyperplasia

 
This reportedly affects as few as 2% of Conn’s syndrome patients.⁵ Primary adrenal hyperplasia is also known as unilateral (one-sided) hyperplasia because it affects just one adrenal gland. It can be treated by surgically removing the affected gland.

Aldosterone-producing adrenocortical carcinoma
This is one of the least likely reasons, occuring in under 1% of cases.⁵ Aldosterone-producing adrenocortical carcinoma (APACC) is a rare type of cancer that develops in the adrenal glands and produces excessive amounts of aldosterone. 

Treatment for APACC usually involves surgery to remove the tumour, followed by close monitoring for recurrence. APACC is a rare condition, hence there is limited information available about its causes and treatment options.

Familial hyperaldosteronism:

There are four known types of familial hyperaldosteronism (FH), which is genetically inherited and causes 1%-5% of Conn’s syndrome cases.⁶ 

All four types of FH arise from different genetic changes. In type I, the affected gene codes for an enzyme involved in aldosterone production. The genetic mutations in types II, III, and IV all lead to a buildup of calcium in adrenal gland cells. Calcium is the signal for these cells to start making aldosterone.⁶ 

Ectopic aldosterone-producing adenoma (APA) or carcinoma

An ectopic APA is a rare type of tumour that produces excessive amounts of aldosterone. It’s established as a reason for Conn's syndrome in less than 0.1% of cases.⁵ Unlike typical APAs, which are found in the adrenal gland, ectopic APAs can be found in other parts of the body, such as the chest or abdomen. Ectopic APAs can cause similar symptoms to other forms of primary aldosteronism, such as high blood pressure, muscle weakness, and fatigue. However, because they are located outside the adrenal gland, they may be more difficult to detect and diagnose.

Signs and symptoms of Conn’s syndrome

Conn's syndrome leads to a range of signs and symptoms, including²:

• High blood pressure: This is the most common symptom of Conn's syndrome. Blood pressure can be difficult to control with medication and may be resistant to treatment.

• Low potassium levels: Aldosterone can cause the body to excrete potassium, which can lead to low levels in the blood. The patient may experience muscle weakness, cramping, fatigue.

• Increased urination: Aldosterone can cause the body to retain salt and water, which can lead to an increase in urine production and frequency.
  
• Headaches: High blood pressure can cause headaches, especially in the morning. 

• Heart palpitations: Sometimes low potassium levels cause abnormal heart rhythms and palpitations.

• Numbness or tingling: Low potassium levels can also cause numbness or tingling in the hands, feet, or face.

• Vision changes: It happens rarely, but patients may notice changes in their vision, such as blurred or double vision.

Management and treatment for Conn’s syndrome

The treatment of Conn's syndrome depends on the underlying cause and severity of the condition. The main goals of treatment are to control blood pressure and correct any sodium & potassium imbalances, particularly low potassium levels. Here are some of the most popular treatment options for Conn's syndrome:

Medications

Medications can be used to control blood pressure and reduce the amount of aldosterone in the body. Angiotensin-converting enzyme (ACE) inhibitors (e.g. enalapril, lisinopril, captopril), angiotensin II receptor blockers (e.g. losartan, valsartan, irbesartan), and various diuretics are commonly prescribed for Conn's syndrome. 

When bilateral adrenal hyperplasia is the underlying cause, treatment is likely to include spironolactone or eplerenone to block the action of aldosterone.⁴ These medications are also given to other Conn’s syndrome patients when surgery isn’t an option.³

FH type I can be treated with glucocorticoids, which decrease aldosterone levels.⁴

Surgery

Surgery is the first-line treatment for patients with an APA or a small unilateral adrenal hyperplasia. Adrenalectomy, the surgical removal of the affected adrenal gland, can significantly reduce blood pressure and improve potassium levels in many cases.³

Lifestyle changes

Making certain lifestyle changes can also help manage Conn's syndrome. These include maintaining a healthy weight, reducing sodium intake, avoiding tobacco and excessive alcohol consumption, and getting regular exercise.

It’s important to realise that if left untreated, Conn's syndrome can lead to complications such as heart disease, stroke, and kidney damage. Treating these complications may involve additional medications or procedures.

Diagnosis of Conn’s syndrome

The process of diagnosing Conn’s syndrome includes these steps: 

1. Blood tests to measure aldosterone and renin (an enzyme that controls aldosterone production). If aldosterone levels are 20 times higher than renin activity, the adrenal gland is likely responsible³  

2. Sodium loading (eating excess salt) followed by blood or urine tests to measure aldosterone. High aldosterone confirms the diagnosis, because this method would suppress it in patients without Conn’s syndrome^3,8 

3. Computed tomography (CT) scans or magnetic resonance imaging (MRI) scans, also can help to identify any abnormalities in the adrenal glands.³ 

4. Adrenal vein sampling to measure aldosterone and cortisol (the ‘stress hormone’) in adrenal veins. If aldosterone levels are at least five times higher than cortisol on one side, this points to an APA in one adrenal gland. Similar levels on both sides indicates bilateral adrenal hyperplasia^3,8

Risk factors

A few factors can increase your risk of developing Conn’s syndrome^2,4,9: 

• Being between 30 and 50 years old 
• Having high blood pressure 
• A family history of Conn’s syndrome 
• Being assigned female at birth

Complications

Unfortunately, complications of Conn’s syndrome are common. High blood pressure can increase the risk of cardiovascular disease if uncontrolled. Over time, high blood pressure and electrolyte imbalances can also damage the kidneys. Excess aldosterone can lead to a loss of calcium from bones, which can increase the risk of osteoporosis.¹⁰

FAQs

Can Conn’s syndrome be prevented?

There are no known ways to prevent Conn's syndrome, but maintaining a healthy lifestyle, such as eating a balanced diet, exercising regularly, and avoiding tobacco and excessive alcohol consumption can help to reduce the risk of developing high blood pressure and other complications.

How common is Conn’s syndrome?

The exact prevalence of Conn's syndrome is unknown, but it is estimated to affect between 1-10% of people with high blood pressure. The estimated prevalence of Conn’s syndrome varies from below 1% to 30% in different studies.⁷ It depends on patient selection and diagnostic methods that researchers use, as well as the location.

When should I see a doctor?

If you have high blood pressure that is difficult to control or experience symptoms such as muscle weakness, frequent urination, or excessive thirst, it is important to see a doctor for evaluation. Your doctor can perform the necessary tests to determine whether Conn's syndrome or another underlying condition is the cause of your symptoms. They will most likely screen you if you meet any of the Endocrine Society’s criteria:

• Stage 2 or stage 3 hypertension
• Hypertension that resistant to 3 blood pressure drugs, including a diuretic
• Hypertension that is only controlled by 4+ blood pressure drugs
• Hypertension with spontaneous or diuretic-induced hypokalaemia
• Hypertension with an adrenal incidentaloma (an adrenal tumour found during a scan for something else)
• Hypertension with a family history of early-onset hypertension or cerebrovascular disease (affecting blood flow to the brain)
• Patients with first-degree relatives diagnosed with Conn’s disease/primary aldosteronism

Summary

Conn's syndrome, also known as primary aldosteronism, occurs when one or both adrenal glands generate more of the hormone aldosterone than normal. This can lead to increased sodium retention and potassium loss in the body, causing high blood pressure, muscle weakness, and fatigue, among other symptoms. 

There are various causes of Conn's syndrome, including bilateral idiopathic adrenal hyperplasia, adrenal adenoma (Conn's disease), primary (unilateral) adrenal hyperplasia, an aldosterone-producing adenoma (APA), familial hyperaldosteronism, and an ectopic APA or carcinoma. 

Depending on the cause, symptoms of Conn's syndrome can vary. The most common symptom is high blood pressure, which may be resistant to treatment. Other symptoms may include low potassium levels, increased urination, headaches, heart palpitations, numbness or tingling, and vision changes. 

It's essential to diagnose and treat Conn's syndrome as early as possible to prevent hypertension from causing heart failure development, heart attacks, strokes, and kidney failure.