Aldosterone

Aldosterone is  a hormone secreted by the adrenal cortex. Aldosterone is a potent mineralocorticoid. Production of Aldosterone is regulated primarily by the renin-angiotensin system. This system works as follows: a decreased effective renal blood flow triggers pressure-sensitive renal glomerular elements to release renin. The renin then stimulates the liver to secrete angiotensin I, which is converted to angiotensin II in the lung and kidney. Angiotensin II is a potent stimulator of Aldosterone.


Secondarily, Aldosterone is stimulated by Adrenocorticotropic Hormone (ACTH), Low Blood Sodium Levels, and High Blood Potassium Levels. Aldosterone in turn stimulates the renal tubules to absorb sodium (water follows) and to secrete potassium in the urine. In this way, Aldosterone regulates blood sodium and potassium levels. Because water follows sodium transport, Aldosterone participates in regulating water absorption (and plasma volume).
Increased Aldosterone levels are associated with primary aldosteronism in which a tumor (usually an adenoma) of the adrenal cortex (Conn syndrome) or bilateral adrenal nodular hyperplasia causes increased production of Aldosterone. The typical pattern for primary aldosteronism is an increased Aldosterone level and a decreased renin level. The renin level is low because the increased Aldosterone level “turns off” the renin-angiotensin system. Patients with primary aldosteronism characteristically have hypertension, weakness, polyuria, and hypokalemia.
Increased Aldosterone levels also occur with secondary aldosteronism caused by nonadrenal conditions. These include the following:

  • Renal Vascular Stenosis or Renal Vascular Occlusion.
  • Hyponatremia (from Diuretic or Laxative abuse) or low salt intake.
  • Hypovolemia.
  • Pregnancy or use of Estrogens.
  • Malignant Hypertension.
  • Potassium Loading.
  • Poor Perfusion States (e.g., Congestive Heart Failure).
  • Decreased Intravascular Volume (e.g., Cirrhosis, Nephrotic Syndrome).

In secondary aldosteronism, Aldosterone levels and renin levels are high.
The Aldosterone assay can be performed on a 24-hour urine specimen or a plasma blood sample. The advantage of the 24-hour urine sample is that short-term fluctuations are eliminated. Plasma values are more convenient to sample, but they are affected by short-term fluctuations. Factors that can rapidly cause fluctuation in Aldosterone levels include the following:

  • Diurnal Variation: Peak Aldosterone levels occur in early morning. In late afternoon the levels are cut in half.
  • Body Position: In the upright position, plasma Aldosterone levels are greatly increased.
  • Diet: Levels of both urine and plasma Aldosterone are increased by low-sodium diets and are decreased by high-sodium diets. (Diets high and low in potassium have the opposite affect.)

Because of these interfering factors, the patient is usually asked to be in the upright position (at least sitting) for a minimum of 2 hours before blood is drawn. Occasionally blood will be drawn again before the patient gets out of bed. The patient will be also required to maintain a normal-sodium diet (approximately 3 g/day) for at least 2 weeks before blood or urine collection.

 

If the patient is taking drugs that alter sodium, potassium, and fluid balance (e.g., Diuretics, Antihypertensives, Steroids, Oral Contraceptives) they should ask their doctor if it is possible to stop taking these medications. The Aldosterone Test results will be more accurate if these drugs are suspended at least 2 weeks before either the blood or urine test. Renin Inhibitors (e.g., Propranolol) should not be taken a week before the test if confirmed by the physician. Patients should also avoid licorice for at least 2 weeks before the test because licorice has Aldosterone-like effect.

 

A 24-hour urine collection is therefore much more reliable because the effect of these interfering factors is dampened.
Primary aldosteronism can be diagnosed by demonstrating little or no increase in renin levels after Aldosterone stimulation (using salt restriction as the stimulant). This is because Aldosterone is already maximally secreted by the pathologic adrenal gland. Also, patients with primary aldosteronism fail to suppress Aldosterone after saline infusion (1.5 to 2 L of normal saline solution infused between 8AM and 10 AM). Aldosterone can be measured in blood obtained from adrenal venous sampling. In this situation, high levels from the right and left adrenal veins are diagnostic of bilateral adrenal hyperplasia. Unilateral high Aldosterone levels are found in patients with Aldosterone-producing tumors of the adrenal gland or renal artery stenosis. Renin levels are usually obtained at the same time. High unilateral renin levels with unilateral high Aldosterone levels indicate renal artery stenosis. Aldosterone-producing tumors of the adrenal gland are characterized by unilateral high adrenal vein Aldosterone and low renin levels.

 

 

 

Causes of Aldosterone False Indications

  • Strenuous Exercise and Stress can stimulate adrenocortical secretions and increase Aldosterone levels.
  • Excessive Licorice Ingestion can cause decreased aldosterone levels, because it produces an aldosterone-like effect.
  • Values are influenced by Posture, Diet, Pregnancy, and Diurnal Variations.
  • Patient position can significantly affect Aldosterone levels.
  • If the test is performed by radioimmunoassay, recently administered radioactive medications will affect test results.
  • Drugs that may cause increased Aldosterone levels include Diazoxide (Hyperstat), Hydralazine (Apresoline), Nitroprusside (Nipride), Diuretics, Laxatives, Potassium, and Spironolactone.
  • Drugs that may cause decreased Aldosterone levels include Angiotensin-converting Enzyme Inhibitors (e.g., Captopril), Fludrocortisone (Florinef), Licorice, and Propranolol (Inderal).

 

 

 

Causes of Aldosterone False Indications

In Blood

Supine: 3-10 ng/dL or 0.08-0.30 nmol/L (SI units)
Upright (sitting for at least 2 hours)

  • Female: 5-30 ng/dL or 0.14-0.80 nmol/L (SI units).
  • Male: 6-22 ng/dL or 0.17-0.61 nmol/L (SI units).
  • Newborn: 5-60 ng/dL.
  • 1 week-1 year: 1-160 ng/dL.
  • 1-3 years: 5-60 ng/dL.
  • 3-5 years: 5-80 ng/dL.
  • 5-7 years: 5-50 ng/dL.
  • 7-11 years: 5-70 ng/dL.
  • 11-15 years: 5-50 ng/dL

 

 

In Urine

2-26 mcg/24 hour collection or 6-72 nmol/24 hour (SI units).

 

 

 

Causes of High Aldosterone Levels

Primary Aldosteronism

In Primary Aldosteronism, Aldosterone is produced in abnormally high quantities by the pathologic adrenal gland. This is reflected in serum and urine levels. Conditions of Primary Aldosteronism include:

  • Aldosterone-producing Adrenal Adenoma (Conn disease).
  • Adrenal Cortical Nodular Hyperplasia.
  • Bartter syndrome (Renal Wasting of Potassium associated with poor sodium tubule absorption).

 

 

 

Secondary Aldosteronism

Aldosterone can be stimulated directly by the following causes:

  • Hyponatremia.
  • Hyperkalemia.
  • Diuretic Ingestion resulting in Hypovolemia and Hyponatremia.
  • Laxative Abuse.
  • Cushing’s Disease: the abnormally high ACTH levels secreted by a Pituitary adenoma act as a direct stimulant to aldosterone.

 

The renin-angiotensin system is stimulated in the following conditions. Renin levels are high, and Aldosterone secretion is stimulated:

  • Stress.
  • Malignant Hypertension.
  • Poor Perfusion States such as Congestive Heart Failure.
  • Decreased Intravascular Volume, including Cirrhosis, Nephrotic syndrome.
  • Renal Arterial Stenosis.
  • Pregnancy and Oral Contraceptives.
  • Hypovolemia or Hemorrhage.

 

 

 

Causes of Low Aldosterone Levels

  • Aldosterone Deficiency.
  • Renin Deficiency: This is very rare and results in Aldosterone Deficiency.
  • Steroid Therapy: ACTH is suppressed and therefore Aldosterone is suppressed.
  • Addison Disease: The adrenal cortex is not functional and therefore Aldosterone cannot be secreted.
  • Toxemia of Pregnancy.
  • Antihypertensive therapy: Some antihypertensive medications inhibit Aldosterone.

 

The following act as potent inhibitors to Aldosterone secretion:

  • Patients on a High-sodium Diet.
  • Hypernatremia.
  • Addison Disease.