What are the causes of primary hyperaldosteronism?

  1. 65% of adult cases are due to aldosterone producing adrenal adenomas (APA). These are benign tumours, usually found in only one adrenal gland, and are between 0.5cm and 2.5cm in diameter. They are normally unresponsive to angiotensin II, but still retain some responses to ACTH (see physiology section). As in all tumours a genetic cause is suspected.
  2. 30% of adult cases are bilateral idiopathic hyperaldosteronism (IHA). This is the most common cause of primary hyperaldosteronism in children. The adrenal glands start to grow excessively to produce nodules, either large (macronodular) or small (micronodular) that secrete aldosterone. These seem to be responsive to angiotensin II but not ACTH. Cause is unknown.
  3. The remaining 5% of cases are due to:
    1. adrenocortical carcinomas (malignant tumours of the adrenal cortex) - 1%
    2. glucocorticoid-suppressible aldosteronism (GSA) - This is a genetic condition inherited in an autosomal dominant pattern, where there is excess production of aldosterone. This excess is due to the fusion of an enzyme promoter gene with the ACTH synthase gene. The excess ACTH produced drives the aldosterone production; therefore suppression of ACTH with dexamethasone suppresses the aldosterone and is the treatment of choice - <2%
    3. primary adrenal hyperplasia - similar to IHA in that the glands are increased in size and nodular, but are sensitive to ACTH and not angiotensin II (as in IHA). The ACTH is normal, and the cause is unknown.
    4. renin-responsive aldosterone producing adrenal adenoma - again this is essentially the same as the common APA but is more responsive to angiotensin II than ACTH.