Pathophysiology
The genes encoding aldosterone synthase and 11-hydroxylase are 95% identical and are close together on chromosome 8. In individuals with GRA, there is unequal crossing over so that the 5' regulatory region of the 11-hydroxylase gene is fused to the coding region of the aldosterone synthase.
The product of this hybrid gene is aldosterone synthase that is ACTH-sensitive in the zona fasciculata of the adrenal gland.
Although in normal subjects, ACTH accelerates the first step of aldosterone synthesis, ACTH normally has no effect on the activity of aldosterone synthase. However, in subjects with glucocorticoid-remediable aldosteronism, ACTH increases the activity of existing aldosterone synthase, resulting in an abnormally high rate of aldosterone synthesis and hyperaldosteronism.
Read more about this topic: Glucocorticoid Remediable Aldosteronism