Q. I am confused as to why high-dose dexamethasone inhibits a pituitary source, but the lower dose does not. Is it just because the cells are hyperplastic and not functioning up to par? Also I am assuming that dexamethasone produces a metabolite different from those produced from endogenous cortisol in urine, right? Otherwise the test wouldn’t be interpretable.

A. Great questions. Regarding the high vs. low dose dexamethasone and pituitary adenomas: the cells in the adenoma are neoplastic. Benign, but still neoplastic. Neoplastic cells generally are usually pretty insensitive to outside stimuli (but they can, in some cases, be affected). I think of those pituitary adenoma cells as being typical neoplastic cells in that they are insensitive to low-dose dexamethasone.

However, if you give a lot of dexamethasone, well, they do respond a little (and decrease their ACTH production). A similar principle operates in Nelson syndrome: the ACTH-producing pituitary adenoma is somewhat kept in check by the negative feedback from all the cortisol floating around. But if you remove the adrenal glands, you remove the negative feedback, and the pituitary adenoma grows explosively.

Regarding measuring dexamethasone in the urine: dexamethasone is an extremely potent steroid – way more potent than cortisol. So to get the same effect as cortisol, you only need to supply a relatively tiny amount of dexamethasone. The amount used in the suppression test is so tiny that it doesn’t affect the measurement of cortisol in the urine.