The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 80

93. How is adrenal insufficiency related to mast cell disease?

Adrenal insufficiency is when the adrenal glands do not make enough cortisol, a stress hormone your body needs to help your body respond to the things happening inside and around it. Not having enough cortisol is dangerous and can be fatal.

Adrenal insufficiency is not the same as adrenal fatigue. Patients with adrenal insufficiency demonstrate lower than normal levels of cortisol. Adrenal fatigue is a term that is used to describe a similar constellation of symptoms as seen in adrenal insufficiency but without the lower than normal serum cortisol level when tested. Adrenal fatigue is not well accepted in main stream medicine.

There are several steps involved in making cortisol. These steps use hormones to tell the body to make other hormones until cortisol is finally made. The molecules that are involved in getting the body to make cortisol are collectively called the HPA axis.

Mast cells interact with the HPA axis a lot and in several ways. I have written extensively about this before.

The activity of the HPA axis can either activate mast cells or stabilize them. It can tell the body to make epinephrine, which decreases mast cell activation. But it can also tell mast cells to make inflammation.

It also works in the other direction. Mast cell activation can activate the HPA axis or not, but it usually activates it. If mast cells generate enough inflammation, that can turn on the HPA axis, which in turn activates mast cells even more. This basically means that if you have frequent mast cell activation, your body can end up in a constant fight or flight response. The inflammation generated can be enormous.

When the body has been in a stress response for too long, the adrenal glands can stop making cortisol, causing adrenal insufficiency. This can cause mast cell activation.

Steroids like prednisone mimic the action of cortisol, the stress hormone. Steroids are sometimes used to treat mast cell disease. The purpose of the steroids is to make cells like mast cells stop causing inflammation. If you take systemic steroids like prednisone routinely, your body can become confused and stop making cortisol on its own. This means that when you stop taking the prescription, your body will not have enough cortisol, causing adrenal insufficiency. This activates mast cells in a huge way. Patients often have a hard time getting back to a good baseline without steroids if they have been on steroids for a while.

There is an autoimmune disease called Addison’s Disease that causes adrenal insufficiency. MCAS sometimes occurs secondary to Addison’s.


For further reading, please visit the following posts:

The effects of cortisol on mast cells: Cortisol and HPA axis (Part 1 of 3)
The effects of cortisol on mast cells: Cortisol and HPA axis (Part 2 of 3)
The effects of cortisol on mast cells: Cortisol and HPA axis (Part 3 of 3)
Corticotropin releasing hormone, cortisol and mast cells
Mood disorders and inflammation: High cortisol and low serotonin