Why I don't believe in Adrenal Fatigue

There's a lot of talk about "Adrenal Fatigue". The claim is, that, due to the stresses of modern living, the adrenal gland can get tired or burned out, and lose the ability to produce enough cortisol. This can result in major fatigue and other symptoms.

Basically, I believe the patients, but I don't believe the doctor's explanation. Here's why.

Among other hormones, the adrenal gland produces cortisol, often termed "the stress hormone". (This is a big misleading -- it has a much broader role in regulating glucose metabolism and the immune system). Cortisol production is regulated by the hypothalamus in the brain, which releases a hormone called CRH, which tells the pituitary to release another hormone called ACTH, which tells the adrenal gland to make cortisol. Long and complicated! But this chain of command is called the HPA Axis -- HPA = Hypothalamus, Pituitary, Adrenal.

The adrenal gland actually atrophies if it does not receive stimulation. This is seen, for example, in patients who take steroids such as prednisone for asthma for an extended time. (Prednisone is a stronger synthetic modification of cortisol). The high levels of prednisone suppress ACTH production, and the adrenal gland will eventually atrophy, making it difficult or impossible to stop the prednisone.

At the other end of the range, some tumors produce high levels of ACTH. This is where, if stress caused the adrenal glands to overwork, we'd see burned out adrenal glands. These high levels of ACTH should produce adrenal fatigue on steroids, so to speak.

But no, instead we get Cushing's Disease, a serious condition defined by high cortisol levels.

So we should dismiss the "fatigue" explanation. I have seen no evidence to support it, nor even a suggested mechanism at a cellular level. Instead, the explanation seems to draw on the intiuitive notion that working hard makes you tired, and that things wear out. A better analogy is muscles -- if you don't use them, they wither away, but if you lift weights and use your muscles, they gain in strength!

But let's not dismiss the patient's complaints! There really are cases where the adrenal glands can't make enough cortisol under stress conditions, or make a bit too little under normal conditions. In addition, there can be problems at the hypothalamus or pituitary.

And let's not dismiss stress as a contributor. There are many things that cause alterations in the behavior of the HPA axis. Prolonged stress and depression are two.

But if we work from the wrong explanation, we can't interpret test results sanely. And it is important to not treat with steroids, without testing first and verifying that there is a problem. If you treat a cortisol deficiency that doesn't exist, you can create the very problem you're treating! (Remember the part about the adrenal gland atrophying if it doesn't receive ACTH stimulation).

I won't discuss adrenal testing in this post. It's a hot topic for me, as I've had it done wrong a couple times, and I want to do it justice. But I will say that single cortisol tests aren't that meaningful, and stimulation tests are needed to understand how the adrenal gland reacts to stimulation. A normal cortisol result can mask an adrenal gland that can't handle the high demands of a major stressor, such as illness or injury.

And what results to consider a problem that should be treated can be an interesting question. Risks vs benefits, with quality of life now often hanging in the balance against long-term risks.

Serious deficiencies in cortisol (Addison's Disease or Adrenal Insuficiency) are life-threatening, and should always be treated.

Unfortunately, some doctors put people on cortisol replacement without adequate testing, or they have patients "try" some hydrocortisone to see if that helps. This creates a lot of problems, not the least of which is that once you're on steroids, it alters the test results, so you can't get the information you need for a real diagnosis.