Aldosterone and Renin-Angiotensin System
Aldosterone and Renin-Angiotensin
- Aldosterone test can be done on plasma (heparin, EDTA, or citrate).
- The serum can also be used.
- Urine 24 hours is collected with boric acid, and during collection, it is refrigerated.
- The patient should be resting and lying position for the first sample.
- The second sample can be taken when the patient is up and at least 4 hours after the first sample.
- The patient should be upright for at least 2 hours to collect the upright sample with unrestricted salt intake.
- Separate the serum/plasma immediately from the cells.
- Aldosterone peak is in the morning.
- 24 hours of urine can also be used to measure aldosterone.
- A urine sample is preferred to avoid the variation in aldosterone levels.
- The urine sample needs to be acidified with strong mineral or boric acid.
- Keep the urine refrigerated or on the ice for 24 hours immediately.
- The patient should be without any medication for 3 weeks.
- The patient should be on a normal sodium diet for 2 to 4 weeks before the test.
- In the case of low K+, it should be treated before the test.
- Label the sample whether the patient was lying or standing.
- AM level is higher than the PM level.
Precautions for Aldosterone and Renin-Angiotensin
- The patient should be on a normal salt diet for at least 2 weeks before taking the sample.
- Diuretics, anti-hypertensive drugs, estrogen, and oral contraceptives should be terminated 2 to 4 hours before taking the sample.
- No radioactive material should be given.
- Transport the sample on ice and freeze it as soon as possible after collecting the sample.
- Stress and exercise can stimulate the increased production of aldosterone by stimulating the adrenal cortex.
- Thermal stress, starvation, and late pregnancy may increase the level.
- Values are affected by posture, diet, pregnancy, and diurnal variation.
- Values are increased by upright posture.
- Increased intake of licorice can decreases the level of aldosterone. Stop it for at least 2 weeks before the sample is taken.
- Drugs like diazoxide, hydralazine, diuretics, nitroprusside, potassium, and laxatives increase the aldosterone level.
- Drugs like propranolol (Inderal) and captopril decrease the aldosterone level.
- Stop the propranolol one week before the sample is taken.
- Heparin therapy may decrease the level.
- Aldosterone level decreases with age.
Indications for the renin-angiotensin and aldosterone
- Used to diagnose hyperaldosteronism.
- It differentiates between primary aldosteronism (Adrenal diseases) and secondary aldosteronism (Extra-adrenal diseases).
- A single random test for aldosterone is of no use unless plasma renin level is done simultaneously.
Pathophysiology for the renin-angiotensin and aldosterone
- Aldosterone is the adrenal gland hormone (produced in the zona glomerulosa of the adrenal cortex), and it helps to control electrolyte balance.
- Aldosterone is the major mineralocorticoid produced by the adrenal cortex at 200 µg/day.
- The main functions of aldosterone:
- It maintains the mineral regulation by its action on the distal convoluted tubule to increase sodium and chloride resorption.
- Aldosterone responds to the change in body volume. It accelerates the reabsorption of the Na+ in the distle tubules in exchange for K+ ions.
- When there is excess production of hormones, Na+ is retained, and K+ is excreted.
- If the hormone’s deficiency, then reverse action occurs, increased Na+ excretion and retention of the K+ ions.
- Aldosterone is secreted at the rate of 150 to 200 micrograms/day, regulating the salt contents and extracellular fluid level.
- In case of profuse sweating, which led to the loss of NaCl and needed to conserve the Na+, that is because of the aldosterone hormone.
- Its action is on the renal distal convoluted tubule.
- It regulates sodium, Chloride, and water resorption in exchange for Potassium excretion and Hydrogen in the kidney.
- Aldosterone helps and maintains blood pressure and blood volume.
The renin-angiotensin system function:
- It controls the secretion of aldosterone.
- Renin is a proteolytic enzyme synthesized and stored in the juxtaglomerular cells located in the terminal part of afferent arterioles.
- The renin-angiotensin system regulates aldosterone secretion.
- The second controller is ACTH which stimulates the production of Aldosterone. It depends upon:
- Low serum sodium level.
- High serum potassium level.
- There is the production of angiotensin, which stimulates the secretion and synthesis of Aldosterone from the adrenal gland.
- Potassium controls the secretion of aldosterone.
- High level of potassium:
- increases the secretion of Aldosterone.
- While low level decreases production.
- Low level of Sodium:
- It causes the release of Renin which again stimulates aldosterone secretion.
- Aldosterone level has a diurnal variation:
- With a peak early in the morning.
- Lower level late in the afternoon.
Clinical significance of Aldosterone:
- Usually, hyperaldosteronism is seen in the adenoma of the adrenal cortex (Conn’s syndrome) or bilateral adrenal nodular hyperplasia.
- An excessive aldosterone level leads to the retention of sodium and potassium excretion.
- There are hypertension and hypokalemia.
- There are weaknesses and polyuria.
Normal Level of Aldosterone
|Supine position||3 to 16|
|Upright||7 to 30|
|Infants and children|
|Infant 3 days||7 to 184|
|1 to 12 months||5 to 90|
|1 to 2 years||7 to 54|
|2 to 10 years|
|Supine||2 to 22|
|Upright||4 to 48|
|Urine level 24 hours||<50 mcg/dL|
- Upright position sitting for 2 hours
- Male = 6 to 22 ng/dL
- Female = 5 to 30 ng/dL
- Newborn = 5 to 60 ng/dL
- Supine = 3 to 10 ng/dL
- Male = 6 to 22 ng/dL
- Female = 5y to 30 ng/dL
- Newborn = 5 to 60 ng/dL
- 1 week to 1 year = 1 to 60 ng/dL
- 3 to 5 years = 5 to 80 ng/dL
- 7 to 11 years = 5 to 70 ng/dL
- 11 to 15 years =5 to 50 ng/dL
- Urine = 2 to 26 µg /24 hours
- Normal in upright position
- Adult = 7 to 30 ng/dL (0.19 to 0.83 nmol/L)
- Adolescent = 4 to 48 ng/dL (0.11 to 1.33 nmol/L)
- Children = 5 to 80 ng/dL (0.14 to 2.22 nmol/L)
- Low- sodium diet = 3 to 5 times higher values
- These patients signs and symptoms are:
- Primary hyperaldosteronism, also called Comm’s syndrome, results from an overproduction of aldosterone, usually by an adrenal cortex adenoma, and other causes are carcinoma and nodular hyperplasia.
- Muscular pains and cramps.
- Low Potassium level.
Causes of primary hyperadrenalism:
- 70% of cases are due to aldosterone-producing tumor-like adrenal cortical adenoma in 54 to 90%.
- CT scan can diagnose 75% of the cases (60% to90%).
- They do adrenal vein catheterization in a few centers and get samples from both side veins. If there is a significant difference between both sides, suggest adenoma.
- 30% of cases are caused by idiopathic bilateral adrenal hyperplasia; the range is 10% to 45%.
- Adrenal carcinoma is seen in <5% of the cases.
- Ectopic production of the aldosterone by the adrenal gland embryologic rest within kidneys, or rarely ovaries.
- Ectopic production of the ACTH or aldosterone by nonadrenal tumors.
- Lab findings are:
- Decreased serum K+.
- Increased aldosterone production can not be suppressed by increasing the volume of Na+ intake.
- There is a diurnal variation of aldosterone, with lower values in the afternoon than in the morning.
- Also, there is an increased level in the upright position.
- There is suppressed plasma renin activity. this is a characteristic lab finding.
- Urinary secretion of aldosterone is increased. Urine estimation has the advantage of eliminating the fluctuation.
- Primary hyperaldosteronism depends on three criteria:
- Hypertension without edema.
- Low plasma renin level that fails to increase with volume depletion.
- Increased aldosterone that fails to decrease with saline or angiotensin inhibition.
- Aldosterone stimulation test.
- Restrict the salt, and the Renin level will show little or no rise.
- Aldosterone suppression test.
- Give normal saline 1.5 to 2 L between 8 AM to 10 AM. Aldosterone will not be suppressed.
- A single random test of aldosterone is of no diagnostic value unless plasma renin activity is done simultaneously.
- Usually associated with extra-adrenal stimulation or non-adrenal causes. e.g.
- Renal vascular stenosis or occlusion.
- Hyponatremia from diuretic or laxatives or low salt intake.
- Malignant hypertension.
- In case of pregnancy or use of estrogens.
- Edematous diseases like congestive heart failure, nephrotic syndrome, or cirrhosis.
- Potassium loading.
Aldosterone Raised Level is seen in:
- In adrenocortical adenoma or carcinoma.
- Bilateral hyperplasia of the adrenal gland.
- Liver diseases.
- Congestive heart failure (CHF).
- Nephrotic syndrome.
- Renovascular hypertension.
Different values of aldosterone and renin in various diseases:
|Causes of the aldosteronism||Aldosterone level||Renin level|
|Cushing’s syndrome||Decreased to normal||Decreased|
|Ingestion of the licorice||Decreased||Decreased|
|High salt diet||Decreased||Decreased|
|Low salt diet||Increased||Increased|
Aldosterone Decreased level is seen in:
- In primary hyperaldosteronism.
- Salt losing diseases.
- Toxemia of pregnancy.
Decreased Aldosterone without hypertension seen in:
- Addison’s Disease.
- Syndrome of hyperaldosteronism due to renin deficiency.
- Isolated cases of aldosterone deficiency.
Decreased Aldosterone with hypertension seen in:
- Excessive secretion of corticosterone.
- Excessive secretion of Deoxycorticosterone.
- Excessive secretion of 18-hydroxydesoxycorticosterone.
- Turner’s syndrome (in some cases).
- Diabetes mellitus.
- Acute alcoholic intoxication.
Clinical conditions of Aldosterone:
|Clinical condition||Aldosterone||Potassium||Blood pressure||Renin activity|
|Secondary hyperadrenalism||Increased||Low or low normal||Usually high||Increased|