Adrenal insufficiency

As shown in the figure on the right, the adrenal gland produces cortisol in response to ACTH (Adrenocorticotropin hormone) produced by the pituitary.

Cortisol is the bodies very own corticosteroid, doing things like supporting blood pressure and suppressing inflammation. Prednisone and dexamethasone are other corticosteroids given pharmacologically. If you don't make your own cortisol, you die unless you get replacement therapy. Tuberculosis is the most common cause of adrenal insufficiency (i.e. cortisol deficiency) worldwide, but autoimmune attack on the adrenal gland is the most common cause in the US. In these cases adrenal insufficiency usually develops slowly, giving the body a chance to adapt. In overwhelming infection, for example, the adrenal can be deprived of blood supply, infarct and cortisol production can be lost suddenly, leading to death unless someone recognizes what is going on and gives replacment therapy.

More rarely, the pituitary or hypothalamus can fail, leading to no ACTH and no cortisol, even though the adrenal is working normally. These are termend secondary (pituitary) and tertiary (hypothalamus) adrenal insufficiency. To distinguish between primary and higher order adrenal insufficiency, endocrinologists do something called an ACTH stimulation test where they inject ACTH and look for a rise in cortisol (endocrinologists love doing tests to either stimulate or suppress secretion of hormones). There are both regular and low-dose ACTH stim tests, but until now, I didn't know why. According to an article in the JAMA (no free text):

The choice of the 250-µg dose is based solely on the fact that ACTH comes in 250-µg vials. However, with this dose, ACTH reaches plasma levels that are approximately 1000 times the values observed in maximally stressed healthy individuals, thereby potentially causing a falsely normal cortisol response by an adrenal gland that is in fact partially impaired

Glad to see they were thinking when they came up with the original test! Hence the development of "low-dose" ACTH stim testss which use just 1ug, a more physiologic dose.

As an allergist, my biggest concern is secondary adrenal insufficiency caused by prolonged use of steroid medications like prednisone. Sometimes even high doses of inhaled steroids can lead to adrenal suppression (patients are on so much steroid medicine the adrenal stops making your own).

Note the steroids discussed here are distinct from the steroids used by most pro athletes.

This "patient page," which accompanies the JAMA article gives more info on adrenal insufficiency