Hyperaldosteronism: Symptoms, Types, Causes and Treatment

Hyperaldosteronism is a hormonal disorder with wide-ranging effects on the body, primarily driven by the overproduction of aldosterone—a key hormone regulating salt and water balance. While it is most famously linked with high blood pressure, its clinical picture is diverse and can sometimes be subtle. Understanding the symptoms, types, underlying causes, and available treatments of hyperaldosteronism is crucial for both patients and healthcare professionals to ensure timely diagnosis and optimal management.

Symptoms of Hyperaldosteronism

Hyperaldosteronism often flies under the radar because many of its symptoms overlap with more common conditions like essential hypertension. However, recognizing the pattern of symptoms can significantly improve outcomes, since targeted treatment can be curative or greatly improve quality of life.

Symptom	Frequency	Clinical Notes	Source(s)
Hypertension	Very Common	Often resistant to standard therapy	1 2 4 13
Hypokalemia	Common	May be intermittent; causes muscle weakness	1 2 4 18
Muscle Weakness	Possible	Sometimes presents as paralysis	1 4 18
Fatigue	Possible	Can be non-specific	14
Polyuria/Polydipsia	Occasional	Due to potassium loss, impaired kidney function	4 14
Metabolic Alkalosis	Occasional	Detected on blood tests	1 4
Weight Loss	Rare	Occasionally reported	3
Hypocalcemia	Rare	May contribute to tetany or cramps	3 4

Table 1: Key Symptoms

Overview of Clinical Presentation

Hyperaldosteronism typically presents with high blood pressure that is often resistant to standard antihypertensive medications. This hypertension can be severe and is sometimes the only symptom, making it easy to overlook the underlying hormonal cause 2 4 13.

Electrolyte Abnormalities and Their Effects

The hallmark laboratory abnormality is hypokalemia (low potassium levels), which can result in:

• Muscle weakness
• Cramps
• In severe cases, paralysis or even tetany (muscle spasms) due to associated metabolic alkalosis and sometimes hypocalcemia 1 4 18.

Some patients experience polyuria (excessive urination) and polydipsia (excessive thirst), which occur because potassium depletion impairs the kidney's ability to concentrate urine 4 14.

Less Common Manifestations

• Fatigue and nonspecific symptoms like headaches may occur.
• Weight loss and hypocalcemia are rare but documented, especially in cases where the disease is prolonged or severe 3 14.
• Some people may be asymptomatic, and the condition is only discovered during evaluation for hypertension or low potassium 2 13.

Types of Hyperaldosteronism

Understanding the different types of hyperaldosteronism is key to selecting the right treatment. Types are generally classified based on the underlying mechanism of excess aldosterone production.

Type	Primary Feature	Distinctive Notes	Source(s)
Primary (Conn's syndrome)	Aldosterone-producing adenoma	Low renin, high aldosterone	1 2 4 13
Idiopathic Hyperaldosteronism (IHA)	Bilateral adrenal hyperplasia	Both glands enlarged; milder symptoms	2 6 13
Familial Hyperaldosteronism (FH)	Genetic/familial forms	Types I–IV; variable inheritance	5 8 9 11
Glucocorticoid-Remediable Aldosteronism (FH-I)	ACTH-driven aldosterone production	Suppressed by dexamethasone	2 13 15
Secondary Hyperaldosteronism	Non-adrenal causes	Due to extra-adrenal stimulation	7 13
Adrenal Carcinoma	Malignant tumor	Rare; severe symptoms	2 4 16

Table 2: Types of Hyperaldosteronism

Primary Hyperaldosteronism

This group is characterized by inappropriately elevated aldosterone production despite low renin levels. The two main subtypes are:

• Conn’s Syndrome (Aldosterone-Producing Adenoma):

  • Typically a benign tumor in one adrenal gland.
  • More common in females and in middle age.
  • Symptoms and biochemical abnormalities are usually more pronounced 1 2 13.

• Idiopathic Hyperaldosteronism (IHA):

  • Caused by bilateral adrenal gland hyperplasia (enlarged glands).
  • Features are similar but often less severe than Conn’s syndrome.
  • Occurs equally in both sexes 2 6 13.

Familial Hyperaldosteronism

Inherited forms are grouped as Familial Hyperaldosteronism (FH), with several subtypes:

• FH-I (Glucocorticoid-Remediable Aldosteronism):
  • Caused by a chimeric gene leading to ACTH-driven aldosterone production.
  • Responds to glucocorticoid (e.g., dexamethasone) treatment 15.
• FH-II:
  • Not glucocorticoid-remediable; mapped to chromosome 7p22 5.
• FH-III:
  • Due to KCNJ5 mutations; can cause early and severe cases, often requiring surgery 8 9.
• FH-IV:
  • Recently described, with distinct genetic characteristics 9 11.

Secondary Hyperaldosteronism

In this type, the adrenal glands are stimulated to produce excess aldosterone due to a problem elsewhere in the body, such as heart failure or kidney disease. It’s less common and not the primary focus of most hyperaldosteronism research 7 13.

Rare Forms

• Adrenal Carcinoma:
  • Very rare but can present dramatically with severe hypertension and electrolyte disturbances 2 4 16.

Causes of Hyperaldosteronism

The underlying causes of hyperaldosteronism range from benign tumors to hereditary syndromes and even rare genetic mutations. Understanding these causes is crucial for both diagnosis and targeted therapy.

Cause	Mechanism	Typical Age/Onset	Source(s)
Aldosterone-producing adenoma	Autonomous aldosterone secretion	30–50s, more in females	1 2 4 13 18
Bilateral adrenal hyperplasia	Idiopathic overproduction	Middle-aged adults	2 6 13
Familial/genetic mutations	Inherited defects (FH types I–IV)	Often early onset	5 8 9 11
KCNJ5/ion channel mutations	Abnormal ion transport in adrenal cells	Variable	6 8 9 10 12
Adrenocortical carcinoma	Malignant overproduction	Any age, rare	2 4 16
ACTH overproduction (FH-I)	Genetic chimerism—ACTH-driven	Childhood/adolescence	15
Secondary causes	Renal disease, heart failure	Any	7 13

Table 3: Causes of Hyperaldosteronism

Tumors and Hyperplasia

• Aldosterone-Producing Adenoma (APA):

  • Most common cause of surgically treatable primary hyperaldosteronism.
  • Driven by somatic mutations in aldosterone-regulating genes, including KCNJ5 and ATP1A1, affecting ion channels and pumps, leading to autonomous aldosterone secretion 1 2 4 10 12 13 18.

• Bilateral Adrenal Hyperplasia (IHA):

  • Accounts for the majority of cases where no adenoma is found.
  • Believed to be due to diffuse or nodular hyperplasia of the zona glomerulosa, sometimes driven by clusters of aldosterone-producing cells harboring gene mutations (e.g., CACNA1D) 6.

Genetic and Familial Causes

• Familial Hyperaldosteronism (FH):

  • Multiple subtypes, each with distinct genetic mechanisms:
    • FH-I: ACTH-dependent due to a chimeric gene; glucocorticoid-responsive 15.
    • FH-II: Linked to chromosome 7p22; not glucocorticoid-responsive 5.
    • FH-III: KCNJ5 mutations; leads to early, severe disease 8 9.
    • FH-IV: Newly described, rare 9 11.

• Ion Channel and Pump Mutations:

  • Mutations in KCNJ5, ATP1A1 (Na/K pump), and other ion transporters disrupt normal adrenal cell function, leading to excess aldosterone production 6 8 9 10 12.

Rare and Secondary Causes

• Adrenal Carcinoma:

  • Malignant tumor that can cause very high aldosterone levels and is associated with severe symptoms 2 4 16.

• Secondary Hyperaldosteronism:

  • Caused by increased renin due to renal artery stenosis, heart failure, or cirrhosis—not primary adrenal disease 7 13.

Treatment of Hyperaldosteronism

Treating hyperaldosteronism is highly effective and can be life-changing, but the approach depends on the underlying type and cause. Advances in diagnosis and therapy have greatly improved patient outcomes.

Treatment	Indication	Outcome/Goal	Source(s)
Surgical removal (adrenalectomy)	Unilateral adenoma/APAs	Often curative for hypertension/hypokalemia	2 13 16 17 18 19
Mineralocorticoid receptor antagonists (spironolactone, eplerenone, amiloride)	Bilateral hyperplasia, inoperable cases	Blood pressure and potassium control	2 13 16 17 19
Glucocorticoid therapy (dexamethasone)	FH-I (glucocorticoid-remediable)	Suppresses aldosterone production	13 15 16
Low-sodium diet	Supportive, especially bilateral IHA	Enhances medication efficacy	17
Conventional antihypertensives	Adjunct if primary therapy insufficient	Blood pressure control	16 18 19

Table 4: Treatment Options

Surgical Treatment

• Unilateral Disease (Adenoma/APAs):
  • Laparoscopic adrenalectomy is the gold standard and can cure or greatly improve hypertension and correct hypokalemia in most patients 2 13 16 17 18 19.
  • Preoperative management with spironolactone is often used to control blood pressure and potassium before surgery 16.
  • Surgery has low operative risk and a high rate of success, though some patients may have persistent mild hypertension postoperatively 18.

Medical Management

• Bilateral Hyperplasia (IHA) and Inoperable Cases:

  • Mineralocorticoid receptor antagonists (spironolactone, eplerenone, or amiloride) are the mainstay of therapy, effectively controlling blood pressure and preventing hypokalemia 2 13 16 17 19.
  • Amiloride is an alternative if spironolactone is not tolerated 2 16.
  • Lifelong therapy is usually necessary 17.

• Glucocorticoid-Remediable Aldosteronism (FH-I):

  • Low-dose glucocorticoids (such as dexamethasone) suppress ACTH, thereby reducing aldosterone levels and controlling blood pressure 13 15 16.
  • Complete suppression is not required and may lead to Cushingoid side effects if over-treated 15.

Adjunctive and Supportive Measures

• Low-sodium diet is recommended to reduce blood pressure and medication requirements, especially in bilateral disease 17.
• Conventional antihypertensives may be used if blood pressure is not controlled with primary therapy 16 18 19.

Special Considerations

• Adrenal Carcinoma: Requires prompt surgical excision due to aggressive behavior 2 4 16.
• Genetic Counseling/Testing: For familial types, genetic testing may guide management and family screening 11 19.

Conclusion

Hyperaldosteronism is a complex endocrine disorder with a broad spectrum of symptoms, types, and causes. Early recognition and tailored treatment are essential for preventing complications such as cardiovascular and kidney disease. Here’s a summary of the main points:

• Key symptoms include hypertension, hypokalemia, muscle weakness, and occasionally more severe metabolic disturbances.
• Types include primary (most notably Conn’s syndrome and idiopathic hyperaldosteronism), multiple familial forms, and secondary causes.
• Causes range from benign adrenal tumors and bilateral hyperplasia to genetic mutations and rare malignancies.
• Treatment is highly effective when tailored to the specific type—unilateral tumors are often cured surgically, while bilateral disease and genetic forms are managed with lifelong medication.

Key Takeaways:

• Hyperaldosteronism is more common than previously thought, accounting for up to 10% of hypertension cases 13.
• Early diagnosis and specialized treatment can prevent serious complications.
• Both surgical and medical therapies are highly effective when matched to the underlying cause.
• Genetic and familial forms require special consideration, including possible family screening.

Understanding hyperaldosteronism empowers patients and clinicians to seek and provide optimal care, transforming outcomes for those affected by this often-overlooked condition.