Conn’s Syndrome

What is Conn’s Syndrome?

Conn’s Syndrome (Primary Hyperaldosteronism or Aldosterone-producing Adrenal Tumor) is a disorder of one or both adrenal glands which results in the increase in the production of aldosterone by these glands (1, 3).

Image 1 – Location of Adrenal Glands

Aldosterone is a hormone which functions primarily to manage blood pressure by regulating the amount of sodium and potassium in the blood (6). An increase in the level of aldosterone causes the body to retain more water and sodium, and in turn eliminate potassium, this results to an increase in the blood pressure. Hyperaldosteronism can either be primary or secondary.

Secondary refers to the problem originating to other parts of the body, these external factors causes the adrenal glands to manufacture too much aldosterone.

Signs and Symptoms

Primary and Secondary hyperaldosteronism have common manifestations which include the following:

Hypertension or High Blood Pressure may cause headaches, blurred vision, and dizziness (2)

Hypercalcemia or High level of calcium in the blood (1)

Hypokalemia or low level of potassium can cause symptoms such as fatigue, numbness, polyuria (increased urination), polydipsia (increased thirst), muscle cramps, and muscle weakness.

Image 2 – Symptoms, Signs of Conn’s Syndrome

Causes

Primary Hyperaldosteronism or Conn’s Syndrome can either be caused by a unilateral or bilateral affectation of the adrenal glands. A unilateral disease is a result of aldosterone-producing tumor or “aldosteronoma” which results in the production of too much aldosterone on the affected gland. On the other hand, in bilateral hyperplasia, both adrenal glands are hyperactive (3).

Image 3 – Pathogenesis of Conn’s Syndrome

Earlier studies suggested that “aldosteronomas” was the more common cause of Conn’s syndrome with a reported 70-80% of all cases. However recent epidemiologic research reveal that occurrence of hyperaldosteronism secondary to bilateral hyperplasia was higher than what was previously been believed.

There are other causes of Conn’s Syndrome, such as familial forms or genetic, ectopic secretion of aldosterone from the kidneys and ovaries, and pure aldosterone-producing adrenocortical carcinomas wherein they behave as aldosteronoma, although the last three that were mentioned were very rare.

Clear distinction on the causes, especially between the aldosterone-producing adenoma and bilateral hyperplasia causes is significant because the treatments for both causes are markedly different (5).

Diagnosis

Screening for Conn’s Syndrome is best done by measuring the aldosterone, renin, and potassium in the blood. If patient has primary hyperaldosteronism, test results will show high level of aldosterone, low or trace of renin, and low or normal potassium level.

Image 4 – Differential Diagnosis of Conns Syndrome

If the result is suggestive of the syndrome, more tests will be given to further confirm the diagnosis. These confirmatory tests will try to lower the hormone level by giving medication, or extra salt via diet or intravenous fluid. If it still results to a high level serum aldosterone and a low level of renin, then the diagnosis is confirmed.

Screening Tests include:

• Plasma aldosterone concentration to plasma renin activity ratio (PAC:PRA ratio)
• This test measures the level of aldosterone and renin in the blood. A high ratio is suggestive of Primary Hyperaldosteronism, however further tests are warranted to ensure the result

Confirmatory Tests include:

Captopril Suppresion Test

Captopril, a hypertensive drugs which is administered via oral route to a patient who is suspected of having hyperaldosteronism. Renin and aldosterone levels are then taken and measured. A confirmed diagnosis is indicated for patient who has a high level of aldosterone and low level of renin in the blood even after administration of the drug.

24-hour Urinary Excretion of Aldosterone Test:

In this test, the patient is instructed to eat a high-salt diet for five days after which the aldosterone in the urine is measured. Normally, the sodium level in the urine after excretion is >200mEq, while the level of aldosterone will just be <10mcg (4).

However, for patients with Conn’s syndrome, aldosterone level will not be alleviated by the salt load, thus resulting in high urinary aldosterone output (3).

Saline Suppresion test

In this test, a saline or salt solution is introduced to the patient via intravenous route. Blood test will be conducted to measure the amount of aldosterone and renin. Confirmed diagnosis will produce high aldosterone level and low level of renin (3).

Treatment

Treatment for this syndrome is very much dependent on what is causing the overproduction of the hormone. With unilateral diseases, presence of benign tumor (adenoma) is best treated by surgical removal or adrenalectomy.

Image 5 – Treatment of Bilateral Adrenal Hyerplasia Vs Aldosterone Producing Adenoma

A minimally invasive approach (laparoscopic) is done to remove the diseased adrenal gland. However there may be cases wherein the presenting tumor is large enough and difficult to remove. In these conditions, the favourable approach becomes the traditional open surgery (3). Meanwhile, medications such as spironolactone and eplenorone are the treatment of choice for Bilateral Adrenal Hyperplasia.

These drugs are aldosterone-antagonist which aim to manage the hypertension of patients having bilateral disease by regulating the amount of sodium, potassium, and water that is present in the blood. Change in diet is also warranted as patients with these conditions are prescribed to prevent intake of foods that have high-salt content.

If this syndrome is left untreated, the patient is at risk of complications that are associated with uncontrolled high blood pressure. If patients will not be properly diagnosed and will not receive appropriate treatment to address the patient’s conditions, this may eventually lead to myocardial infarction, renal failure, and cerebrovascular accident (3).

Image 6 – Management Options of Conn’s Syndrome

References:

1. Hyperaldosteronism- primary and secondary. MedlinePlus. Retrieved from https://medlineplus.gov/ency/article/000330.htm.
2. Primary hyperaldosteronism (Conn’s syndrome). Columbia University Medical Center. Retrieved from http://columbiasurgery.org/conditions-and-treatments/primary-hyperaldosteronism-conns-syndrome.
3. Primary hyperaldosteronism (Conn’s syndrome or aldosterone-producing adrenal tumor. The American Association of Endocrine Surgeons. Retrieved from http://endocrinediseases.org/adrenal/hyperaldosteronism.shtml.
4. Test 15150: Aldosterone with Sodium, 24 hour, Urine Clinical Information. Mayo Clinic. Retrieved from http://www.mayomedicallaboratories.com/interpretive-guide/?alpha=A&unit_code=15150.
5. Uwaifo, G. (2016) Primary Aldosteronism. Retrieved from http://emedicine.medscape.com/article/127080-overview.
6. What is Aldosterone? (2016) Hormone Health Network. Retrieved from http://www.hormone.org/hormones-and-health/what-do-hormones-do/what-does-aldosterone-do.