Why do people with cushing's get hypertension when aldosterone is normally controlled by renin, not ACTH?

Question

why?

Answer 1

Primary hyperaldosteronism is actually Conn's syndrome, not Cushing's.  Cushing's disease (or syndrome, depending on whether the dysfunction is pituitary or adrenal/ectopic) is hypercortisolism.

However, to answer your question about hypertension in Cushing's, the excess cortisol has a vasoconstrictive effect, plus, in high enough concentrations, it will actually act like aldosterone--both are steroid hormones.  ACTH will in fact increase the production of all the adrenally-produced hormones; both cortisol and aldosterone and even the androgens, so that probably has an effect as well.

Answer 2

The hypertension is caused by the excess cortisol, it is not due to aldosterone.

Aldosterone acts on its target tissues via the mineralocorticoid receptor. The problem is, this receptor is not specific for aldosterone. Cortisol can bind to it just as easily as aldosterone can. There is loads more cortisol in our bodies than aldosterone, so why doesn't the cortisol swamp the receptor and give us permanent hypertension?

The reason for this is that wherever you find the mineralocorticoid receptor, you also find an enzyme called 11-beta-hydroxysteroid dehydrogenase. This enzyme grabs the cortisol before it gets to the receptor, and converts it into cortisone, which doesn't bind to the receptor.

In Cushing's, there is too much cortisol and 11-beta-hydroxysteroid dehydrogenase is overwhelmed, so cortisol escapes and binds to the mineralocorticoid receptor and causes hypertension.