Why Does It Happen?
There are two main types:
Primary Hyperaldosteronism (Problem in the adrenal glands)
Secondary Hyperaldosteronism (Problem outside the adrenal glands)
Common Symptoms:
How Is It Diagnosed?
Blood Tests:
Special Tests:
Imaging Tests:
Genetic Testing: In suspected genetic causes.
Treatment Options:
Medications:
Surgery:
Lifestyle Changes:
Key Points to Remember:
This overview simplifies the complex process of hyperaldosteronism to help understand its causes, symptoms, and treatments.
Aldosterone is synthesized in the adrenal cortex from cholesterol. Aldosterone inhibits the excretion of sodium in the kidney and increases the excretion of potassium. It belongs to the mineralocorticoids. By inhibiting sodium excretion, it increases blood volume and, consequently, blood pressure.
Aldosterone is regulated by the Renin-Angiotensin-Aldosterone System (RAAS).
The renal corpuscles (glomeruli) are small vascular tufts in the kidney where water and electrolytes are excreted to form the primary urine. In the renal tubules, water and electrolytes are partially reabsorbed. Larger blood components are retained and not excreted. The small blood vessel leading to the renal corpuscle is called the afferent arteriole.
The juxtaglomerular apparatus of the kidney is a functional unit located in the glomerulus and is situated near the afferent arteriole. It measures blood pressure in the afferent arteriole and the concentration of sodium and potassium in the renal tubules.
The enzyme renin is stored in renin granules near the afferent arteriole. Renin is released when:
The renal corpuscles are underperfused.
Blood pressure drops.
The quantity of fluid filtered in the renal corpuscles decreases.
A reduced concentration of salt (sodium chloride) is measured in the urine.
Activation of the sympathetic nervous system also leads to the release of renin.
Renin activates the conversion of angiotensinogen into angiotensin I, which is further converted into angiotensin II. Angiotensin II stimulates the release of aldosterone and also acts directly on the angiotensin receptor. This leads to vasoconstriction, increased sodium reabsorption, and, consequently, an elevation in blood pressure.
In patients with arterial hypertension, primary hyperaldosteronism occurs in 0.3 to 1% of cases. In the case of an adrenal incidentaloma, the preference for a Conn’s adenoma is 2-4%. Conn’s adenoma primarily occurs in the 3rd to 5th decades of life.
Causes of primary hyperaldosteronism:
An aldosterone-producing adrenal adenoma (Conn’s adenoma) is the most common cause of primary hyperaldosteronism, accounting for 70-80% of cases.
In idiopathic hyperaldosteronism, plasma renin activity is suppressed. Aldosterone is produced in response to stimulation by angiotensin II, leading to homogeneous or micronodular adrenal hyperplasia.
Primary macronodular adrenal hyperplasia results in autonomous production of aldosterone by one or both adrenal glands.
Glucocorticoid-remediable hyperaldosteronism (familial hyperaldosteronism type I) is caused by a genetic defect. Under the influence of normal ACTH, there is excessive aldosterone production. Characteristically, there are significantly elevated levels of 18-OH-cortisol and 18-oxocortisol. Aldosterone levels drop in the orthostatic test. Diagnosis is made through genetic analysis or, alternatively, by treatment with dexamethasone 0.5-1 mg twice daily for several weeks (beware of iatrogenic Cushing syndrome).
Adrenal carcinoma (very rare, 1 in 1.7 million cases) is hormone-inactive in about 20% of cases. Hormone-active adrenal carcinomas produce cortisol and/or androgens. Hyperaldosteronism is a rarity.
Pseudohyperaldosteronism presents with clinical findings resembling hyperaldosteronism, but aldosterone itself is suppressed, and the mineralocorticoid effect is caused by other substances. Causes may include enzyme defects in cortisol metabolism with an increased production of mineralocorticoid-effective metabolites such as DOC or DOC-producing adrenal tumors. “Apparent mineralocorticoid excess syndrome” results from a defect in 11β-HSD, causing mineralocorticoid activity of cortisol, while Liddle’s syndrome leads to aldosterone-independent retention of sodium and water in the kidneys. Excessive mineralocorticoid dosing also results in pseudohyperaldosteronism.
The symptoms of patients with hyperaldosteronism are nonspecific. Most commonly, polyuria, nocturia, muscle weakness, headaches, and polydipsia are observed. Less frequently, intermittent paralysis, intermittent tetany, fatigue, and muscle pain occur. Arterial hypertension, hypokalemia, and elevated serum aldosterone are always present. Proteinuria, hyposthenuria, EKG changes, and hyponatremia are also frequently found.
Investigation:
Hypertension (High Blood Pressure): Determination of Plasma Potassium. If it falls within the middle to upper normal range, primary hyperaldosteronism is unlikely. If potassium is low, determine plasma renin activity. If plasma renin activity falls within the middle to upper normal range, secondary hyperaldosteronism is likely.
If plasma renin activity is suppressed, determine aldosterone and 18-OH-corticosterone in serum, as well as aldosterone, tetrahydroaldosterone, aldosterone-18-glucuronide, and 18-OH corticosterone in urine.
If these values are low, pseudohyperaldosteronism is present. If these values are elevated, primary hyperaldosteronism is likely. Further evaluation may include the following tests: orthostatic test, Lasix test, salt-loading test, and captopril test.
If basal aldosterone is elevated, can not be suppressed by salt loading or captopril, or there is no increase after Lasix/orthostasis, it indicates an aldosterone-producing adenoma.
If basal aldosterone is elevated, can be suppressed by salt loading/captopril, or there is an increase after Lasix/orthostasis, it indicates idiopathic hyperaldosteronism or hyperplasia.
Functional tests for differentiating hyperaldosteronism:
Prerequisites: Discontinue diuretics, ACE inhibitors, and preferably all other antihypertensive medications, no low-salt diet, at least 4 hours of bed rest before the test.
Stimulation of renin activity due to volume loss and sodium excretion in urine after administration of Lasix.
Measure renin, aldosterone, and 18-OH-C levels in the morning after strict bed rest. Then administer 40 mg of Lasix. Repeat blood draw after 2 hours.
Orthostatic Test:
Stimulation of renin activity due to volume shift after orthostasis.
Measure renin, aldosterone, and 18-OH-corticosterone levels in the morning after strict bed rest. Then instruct the patient to walk around for the next 2 hours. Repeat blood draw after 2 hours.
Interpretation of both tests:
Normal: Stimulation of renin, aldosterone, and 18-OH-corticosterone.
Aldosterone-producing adenoma: Basally elevated levels of renin, aldosterone, and 18-OH-corticosterone, no stimulation or even paradoxical decrease during the test.
Idiopathic hyperaldosteronism: Basally elevated levels of renin, aldosterone, and 18-OH-corticosterone, significant stimulation during the test.
Salt Loading Test:
Suppression of the Renin-Aldosterone-Angiotensin System (RAAS) by salt loading.
Infuse 2 liters of isotonic saline solution over 4 hours (patient lying down). Measure renin, aldosterone, 18-OH-corticosterone, ACTH, cortisol, potassium, sodium before and after salt infusion.
Normal: Suppression of renin, aldosterone (reduction of aldosterone by at least 50%, cut-off less than 85 ng/L), and 18-OH-corticosterone.
Aldosterone-producing adenoma: No suppression, no reduction of aldosterone by less than 50% or less than 85 ng/L.
Idiopathic hyperaldosteronism: Incomplete suppression.
Causes: Renal artery stenosis, malignant nephrosclerosis, renin-producing renal tumor, ectopic renin production, pheochromocytoma (stimulation of renin production by catecholamines).
Renin-producing tumors are more common in women, with a ratio of 2:1 compared to men.
Renal sodium loss, Bartter syndrome (impaired renal sodium reabsorption), Pseudo-Bartter syndrome (due to diuretic abuse, laxative abuse, clandestine vomiting), liver cirrhosis, persistent congestion, heart failure, diabetes insipidus, sodium deficiency, volume depletion, pregnancy.