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Primary Aldosteronism

Primary aldosteronism (PA), also known as primary hyperaldosteronism or Conn's syndrome, involves the overproduction of aldosterone by the adrenal glands, leading to low renin levels and high blood pressure. This condition is often caused by adrenal hyperplasia or tumours. Approximately 35% of cases are due to a single aldosterone-secreting adenoma, termed Conn's syndrome.

Aldosterone
Aldosterone

Signs and Symptoms

Patients with PA often exhibit few or no symptoms. Common manifestations include high blood pressure, muscular weakness, and muscle spasms. Other symptoms include poor vision, confusion, headaches, tingling sensations, dizziness/vertigo, nocturia, and excessive urination. Complications can be severe, involving cardiovascular diseases such as stroke and myocardial infarction, kidney failure, and abnormal heart rhythms.

Causes

Two slices of an adrenal gland with a cortical adenoma, from a person with Conn's syndrome
Two slices of an adrenal gland with a cortical adenoma, from a person with Conn's syndrome

PA can arise from several causes:

  • Bilateral idiopathic adrenal hyperplasia (66% of cases)
  • Adrenal adenoma (Conn's disease) (33% of cases)
  • Primary unilateral 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)

Genetically, 40% of patients with adrenal aldosterone-producing adenoma have somatic gain-of-function mutations in the KCNJ5 gene. Other genes implicated include ATP1A1, ATP2B3, CACNA1D, and CTNNB1.

Pathophysiology

Aldosterone significantly affects kidney function by increasing sodium reabsorption and potassium excretion, leading to sodium retention and plasma volume expansion, which elevates blood pressure. This process can result in hypernatraemia, hypokalaemia, and metabolic alkalosis. These changes stimulate the sodium-potassium ATPase in muscle cells and sodium reabsorption throughout the intestine and nephron, leading to clinical manifestations.

Diagnosis

Diagnosing PA involves measuring both renin and aldosterone levels to calculate the aldosterone-to-renin ratio (ARR). A high ARR suggests PA. Confirmatory tests include saline suppression, ambulatory salt loading, or fludrocortisone suppression tests. Imaging studies like CT scans can identify adrenal abnormalities, and adrenal venous sampling (AVS) may be necessary to localise aldosterone hypersecretion sources.

Treatment

Treatment depends on the underlying cause. For patients with a single benign tumour (adenoma), surgical removal (adrenalectomy) can be curative. This procedure is typically performed laparoscopically. For bilateral adrenal hyperplasia, aldosterone antagonists like spironolactone or eplerenone are used. Spironolactone has antiandrogen effects, leading to side effects such as gynecomastia and irregular menses, which occur less frequently with eplerenone. Esaxerenone and Finerenone are newer non-steroidal mineralocorticoid blockers showing promise in treatment.

Epidemiology

PA is more prevalent than previously thought, affecting up to 12.7% of patients in primary care and 29.8% in referral centres. It occurs more frequently in women than men and typically begins between 30 and 50 years of age. Conn's syndrome is named after Jerome W. Conn, who described the condition in 1955.

Society and Culture

The Primary Aldosteronism Foundation aims to improve diagnosis and treatment for PA by raising awareness, fostering research, and supporting patients and healthcare professionals globally.


Self-assessment MCQs (single best answer)

What is another name for Primary Aldosteronism (PA)?



Which hormone is overproduced in Primary Aldosteronism?



What percentage of PA cases are due to a single aldosterone-secreting adenoma?



Which gene is commonly associated with somatic gain-of-function mutations in adrenal aldosterone-producing adenoma?



What is a common symptom of Primary Aldosteronism?



Which confirmatory test is used for diagnosing PA?



What is the primary treatment for a single benign aldosterone-secreting adenoma?



Which mineralocorticoid receptor antagonist is known for having antiandrogen effects?



What is the typical onset age range for Primary Aldosteronism?



Which organisation aims to improve the diagnosis and treatment of PA?



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