Primary aldosteronism

See ((Aldosterone))

Can cause hypokalemia and hypertension.

12-24% of patients may not show significant hypokalemia.

Plasma aldosterone:renin ratio greater than 100.

Primary aldosteronism (PA), also known as Conn’s syndrome, refers to the excess production of the hormone aldosterone from the adrenal glands.



It results  in low renin levels.



It may be caused by hyperplasia or tumors. 



It is associated with fatigue, potassium deficiency and hypertension  which may cause poor vision, confusion or headaches.


Symptoms of primary aldosteronism may include: muscular aches and weakness, muscle spasms, low back and flank pain from the kidneys, trembling, tingling sensations, numbness and excessive urination.

Complications of PA include cardiovascular disease such as stroke, myocardial infarction, kidney failure and abnormal heart rhythms.

Usual onset occurs  at 30 to 50 years of age.

Causes of primary PA:

Enlargement of both adrenal glands

Adrenal adenoma

Adrenal cancer

Familial hyperaldosteronism

About 33% of cases are due to an adrenal adenoma that produces aldosterone, and 66% of cases are due to an enlargement of both adrenal glands.


Blood test for aldosterone-to-renin ratio



Spironolactone, eplerenone, low salt diet

Frequency accounts for 

10% of patients with hypertension 

Screening is usually done by measuring the aldosterone-to-renin ratio in the blood, with further testing used to confirm positive results.

Low blood potassium is classically described, but is only present in about a quarter of people.

Some cases may be cured by removing the adenoma by surgery: a single adrenal gland may also be removed in cases where only one is enlarged.

With bilateral adrenal enlargement, treatment is typically with medications known as aldosterone antagonists such as spironolactone or eplerenone.

Other  antihypertensives and a low salt diet may also be needed.

Some patients  with familial hyperaldosteronism may be treated with the steroid dexamethasone.

Primary aldosteronism is present in about 10% of people with high blood pressure, and  is  more often in women than men.

Its onset occurs in those between 30 and 50 years of age.

With primary aldosteronism there are  few or no symptoms: 

occasional muscular weakness, muscle spasms, tingling sensations, or excessive urination.

Hypertension, muscle cramps due to hyperexcitability of hypocalcemia, muscle weakness due to hypoexcitability of skeletal muscles secondary to hypokalemia, and headaches may be seen.

Secondary hyperaldosteronism is often related to decreased cardiac output which is associated with elevated renin levels.

Primary and aldosteronism causes:

Bilateral idiopathic adrenal hyperplasia: 66% of cases

Adrenal adenoma (Conn’s disease): 33% of cases

Primary adrenal hyperplasia: 2% of cases

Aldosterone-producing adrenocortical carcinoma: <1% of cases

Familial Hyperaldosteronism (FH)

Glucocorticoid-remediable aldosteronism (FH type I): <1% of cases

FH type II (APA or IHA): <2% of cases

Ectopic aldosterone-producing adenoma or carcinoma: < 0.1% of cases

Patients with an adrenal aldosterone producing adenoma have somatic gain-of-function mutations in a single gene (KCNJ5) in 40% of cases.

KCNJ5 gene is mutated in inherited cases of early onset primary aldosteronism and bilateral adrenal hyperplasia, though  less frequently.

KCNJ5 mutations tend to occur in young women with the adenoma in the cortisol secreting zona fasciculata. 

Adenomas without this mutation tend to occur in older men with resistant hypertension.

Aldosterone has effects on most or all cells of the body.

Aldosterone’s most important actions are in the kidney, on cells of the late distal convoluted tubule and medullary collecting duct. 

Aldosterone increases activity of basolateral membrane sodium-potassium ATPase and apical epithelial sodium channels, as well as potassium channels.

Aldosterone actions on the kidney increases sodium reabsorption and potassium secretion. 

More sodium is reabsorbed than potassium secreted, making the lumen more electrically negative, causing chloride to follow sodium. 

Water retention then follows the sodium and chloride by osmosis, causing increased extracellular sodium and fluid volume with reduced extracellular potassium. 

Aldosterone causes  proton secretion that acidifies urine and alkalizes extracellular fluid.

Hyperaldosteronism causes hypernatremia, hypokalemia, and metabolic alkalosis.

Aldosterone stimulates sodium-potassium ATPase in muscle cells, increasing intracellular potassium and also increases sodium reabsorption all along the intestine and nephron, possibly due to widespread stimulation of sodium-potassium ATPase. 

Its sodium retention leads to plasma volume expansion and elevated blood pressure. 

Primary aldosteronism increases blood pressure and leads to increased glomerular filtration rate and causes a decrease in renin release from the granular cells of the juxtaglomerular apparatus in the kidney decreasing sodium reabsorption and returning sodium renal excretion to near normal levels allowing sodium to escape the effect of mineralocorticoids.

In primary hyperaldosteronism, the decreased renin, and subsequent decreased angiotensin II, will not result  in a decrease in aldosterone levels.

Measuring aldosterone alone is not considered adequate to diagnose primary hyperaldosteronism. 

Both renin and aldosterone are measured, and a resultant aldosterone-to-renin ratio (ARR) is used for case detection.

A high aldosterone-to-renin ratio suggests the presence of primary hyperaldosteronism. 

Diagnosis is made by performing a saline suppression test, ambulatory salt loading test, or fludrocortisone suppression test.

Measuring sodium and potassium concentrations simultaneously in serum and urine specimens is  suggested for screening purposes.

CT scanning can confirm the presence of an adrenal abnormality, possibly an adrenal cortical adenoma (aldosteronoma), adrenal carcinoma, bilateral adrenal hyperplasia, or other less common changes. 

Adrenal venous sampling can clarify the cause in the presence of adrenal abnormalities, especially with bilateral disease.

If adrenal venous sampling in unavailable 

PET/CT using the radiotracer 11C-Metomidate is an option.

Differential diagnosis: 

Liddle syndrome, ingestion of licorice and other foods containing glycyrrhizin. 

The treatment is dependent on the underlying cause. 

With a single benign adenoma, surgical adrenalectomy may be curative. 

With bilateral hyperplasia successful treatment is often achieved with spironolactone or eplerenone, drugs that block the effect of aldosterone. 

In the absence of treatment, patients  with hyperaldosteronism often have poorly controlled high blood pressure, which may be associated with increased rates of stroke, heart disease, and kidney failure. 



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