Aldosterone

What is aldosterone?

Aldosterone is a steroid hormone (a mineralocorticoid) produced in the outermost layer of the adrenal cortex (zona glomerulosa). The hormone is a key player in the body's fine-tuning of blood pressure, fluid balance, salt (sodium) balance, and potassium regulation. Aldosterone is part of the body's blood pressure and fluid regulation system, often called the RAAS (renin–angiotensin–aldosterone system). When the body senses that blood volume or blood pressure is too low, or when potassium in the blood rises, aldosterone production may increase.

How is aldosterone controlled?

Aldosterone is released primarily in response to:

• Angiotensin II (via RAAS, often in cases of low circulating blood volume/lower blood pressure)
• Elevated potassium in the blood
• Sympathetic nervous system (stress/”alarm” signaling that can affect the RAAS)

What does aldosterone do in the body?

Aldosterone acts primarily in the distal tubules and collecting ducts of the kidneys where it:

• increases the reabsorption of sodium (salt) back into the blood
• increases the excretion of potassium in the urine
• leads to water following sodium (osmosis) → increased blood volume → higher blood pressure

Aldosterone can also affect salt and fluid balance via the intestine, but the most clinically important effect is via the kidneys.

Why is P-Aldosterone measured?

P-Aldosterone is analyzed primarily to investigate whether the body's blood pressure and salt balance regulation is working properly. The most common question is whether high blood pressure can be due to a hormonal cause, especially primary hyperaldosteronism (Conn's syndrome), where the adrenal glands produce too much aldosterone.

The analysis may also be relevant in unclear disorders in potassium (low or sometimes high potassium), in rapidly onset or worsening hypertension (especially in younger people), and in cases of suspicion of secondary hypertension, for example in kidney-related influences that activate the RAAS system. First and foremost, aldosterone is almost always measured together with renin, since it is the relationship between them that is often most diagnostically valuable. When both renin and aldosterone are analyzed, the laboratory can calculate the aldosterone/renin ratio (often called the ARR ratio), which is used as a screening tool to determine whether further investigation is needed.

Common indications for sampling

• Investigation of high blood pressure where primary hyperaldosteronism (Conn's) is suspected.
• Rapid onset or worsening hypertension, especially in younger people.
• Suspected of other secondary hypertension (e.g. renovascular hypertension).
• Unclear potassium disorders – both hypokalemia and sometimes hyperkalemia depending on the question.

Please Note! In some follow-up situations, renin alone may be relevant, but in the diagnosis of aldosterone-related conditions, the combination of renin + aldosterone is often central.

What can cause high aldosterone (or high ARR ratio)?

1) Primary hyperaldosteronism (common and important cause). In primary hyperaldosteronism, the adrenal gland produces “too much aldosterone” more or less independently of the body’s normal control. Common causes are:

• Adrenal cortical adenoma (aldosterone-producing adenoma)
• Adrenal cortical hyperplasia (enlarged/overactive tissue)
• More rarely, other adrenal changes

Typically, high aldosterone is seen in combination with low renin → elevated ARR ratio.

2) Secondary aldosterone elevation (RAAS is activated). If the RAAS is “turned on” for other reasons, both renin and aldosterone may be elevated, for example in:

• Renovascular effects (e.g. renal artery stenosis)
• Certain kidney diseases
• Heart failure
• Liver disease with circulatory effects

Symptoms and signs that may be consistent with excess aldosterone

Many people have few clear symptoms, but common findings/signs may include:

• High blood pressure (sometimes difficult to treat)
• Low potassium (hypokalemia) – can cause fatigue, muscle weakness, cramps
• Headache
• Increased thirst and/or increased urine output (sometimes)
• Palpitation or rhythmic sensation (can occur with potassium disorders)

What can low aldosterone (or low aldosterone production) mean?

Low aldosterone levels can be seen when the adrenal gland does not produce enough (or when signaling in the RAAS is disrupted). A classic pattern is low aldosterone in combination with high renin in adrenal insufficiency.

Examples of conditions where low aldosterone can occur

• Adrenal insufficiency (primary) – can cause low aldosterone and high renin
• Certain forms of kidney damage can alter renin/aldosterone regulation
• Drug effects can sometimes lower aldosterone and/or indirectly affect the interpretation

Symptoms that can be seen with low aldosterone/electrolyte disturbance

• Low blood pressure, dizziness (especially when standing up)
• Fatigue and weakness
• Salt craving (may occur)
• Signs of high potassium (hyperkalemia) in certain situations

Aldosterone/Renin Ratio (ARR) – why is it important?

The ARR ratio is used as a screening tool for suspected primary hyperaldosteronism. A typical picture of primary hyperaldosteronism is:

• High aldosterone
• Low renin
• → high ARR ratio

Many laboratories use limits where a clearly elevated ratio indicates further investigation. Interpretation always needs to be done in relation to the conditions of the sample collection, body position, salt intake, potassium level and ongoing medication.

Sampling and important preparations for Aldosterone

Aldosterone and renin are affected by several factors. In order for the test to be as reliable as possible, the sampling is often standardized.

• Morning testing is often recommended.
• Body position before sampling is important: reference intervals can differ between lying down and standing/upright.
• The sample is often taken after standing/walking for about 30 minutes (and then sitting down for sampling) or lying down for about 30 minutes if lying down sampling is used.
• Aldosterone is usually not measured “alone” but together with renin to enable calculation of ARR.

Medications and other sources of error

Several medications can affect renin, aldosterone and thus the ARR ratio. Examples of medications that often need to be considered:

• Beta blockers
• Oestrogen
• Spironolactone/Eplerenone (mineral corticoid receptor blocker)
• Amiloride

Also licorice and high salt intake can affect the system (and can, for example, contribute to low renin), which can make interpretation more difficult.

Important: Never change blood pressure medication on your own before testing. If primary hyperaldosteronism is suspected, more extensive patient preparation and sometimes medication adjustment may be needed in consultation with the treating physician/endocrinologist.

Aldosterone Reference Range

The reference range for aldosterone and renin varies between laboratories and is affected by body position and sometimes method. Therefore, you should always compare your result with the reference range stated on your test result.

When primary hyperaldosteronism is suspected, the following is often considered:

• The level of the ARR ratio
• The level of the aldosterone (not just the ratio)
• Potassium value at the same sampling
• Clinical picture: blood pressure, medications, symptoms and comorbidities