Does adrenal insufficiency with unregulated inflammation cause flares?

Posted by DadCue @dadcue, Aug 25, 2023

Prednisone is a strong anti-inflammatory. However, prednisone also causes adrenal insufficiency.

Inflammation is a good thing as long as it is regulated. Inflammation is when an army of beneficial white blood cells flow in to fight infections and help the body heal itself. We need a certain amount of inflammation to be healthy.

With autoimmune disorders, instead of the inflammation returning to normal levels, the inflammation persists over time and becomes chronic inflammation. We end up needing some prednisone to manage the inflammation.

Cortisol manages an inflammatory response and regulates inflammation. Does adrenal insufficiency cause flares because cortisol levels are inadequate to regulate inflammation???

Exogenous cortisol (prednisone) suppresses the endogenous cortisol that our adrenals should produce. When the adrenals don't produce enough cortisol -- maybe flares are the result. We resort to taking more prednisone (exogenous cortisol) to offset the endogenous cortisol that the adrenals aren't producing. Unfortunately, when we take prednisone, we suppress the production of endogenous cortisol from our adrenals.

It seems like a catch-22 to me. Taking prednisone becomes a difficult situation because it is the answer to the problem but maybe it is also the cause of the problem with recurring flares.

Interested in more discussions like this? Go to the Polymyalgia Rheumatica (PMR) Support Group.

mijaka011 | @mijaka011 | Aug 29, 2023

In reply to @dadcue "Actemra" + (show)

Thank you.

DadCue | @dadcue | Aug 29, 2023

In reply to @christopherc "Thanks for sharing your story about this very important aspect of PMR and prednisone. Adrenal insufficiency..." + (show)

My first dose of Actemra was January 1st, 2019. I started with injections every 2 weeks. I was taking 10 mg of prednisone which was the lowest dose I was on during 12 years of prednisone treatment for PMR. My rheumatoogist didn't want me to take prednisone for the rest of my life.

Secondary adrenal insufficiency is a side effect of long term prednisone use. My primary symptom was overwhelming fatigue but adrenal insufficiency can also cause pain that mimics PMR.

From 10 mg of prednisone I was able to reduce my prednisone dose to 3 mg. I reduced by 1 mg per month for the first 3 months after Actemra was started. I felt well so after that I reduced prednisone by 1 mg per week until I reach 3 mg.

My rheumatologist wanted me to stay on 3 mg when my a.m. cortisol level was low. The lab test confirmed secondary adrenal insufficiency from long term prednisone use. I had to stay on 3 mg of prednisone until I could be seen by an endocrinologist. I was on 3 mg of prednisone for about 6 months until my cortisol level improved. That was when my endocrinologist said my cortisol level was adequate and it might be safe to discontinue prednisone.

I had PMR relapses when Actemra was stopped. I have taken Actemra almost 5 years now except for a couple of interruptions. My dose of Actemra has changed from injections every 2 weeks to injections weekly. This past year I have done monthly IV infusions of Actemra.

My side effects from Actemra are minimal if any. I had many side effect from long term prednisone use that are now improving. I have discontinued five medications that I was taking to treat prednisone side effects.

My rheumatologist thinks PMR might be in remission. Currently there is no plan to stop the monthly Actemra infusions because of the risk of other autoimmune conditions recurring. Actemra was used to treat PMR only but seems to help my other conditions too.

christopherc | @christopherc | Aug 30, 2023

In reply to @dadcue "My first dose of Actemra was January 1st, 2019. I started with injections every 2 weeks...." + (show)

Thanks so much for this thorough and thoughtful response. It’s very helpful to me and I’m sure to many other members of this group. I hope the Actemra continues to work for you and you are truly in remission and stay there.

DadCue | @dadcue | Aug 30, 2023

In reply to @christopherc "Thanks so much for this thorough and thoughtful response. It’s very helpful to me and I’m..." + (show)

The following link talks about a research study with Actemra (tocilizumab) for the treatment of PMR. So far, Actemra still isn't FDA approved for PMR. However, Actemra is FDA approved for the treatment of GCA.
https://www.medpagetoday.com/rheumatology/generalrheumatology/100815
This link might work better:
https://www.ajmc.com/view/tocilizumab-leads-to-improvement-in-patients-with-active-polymyalgia-rheumatica-despite-prednisone-therapy
I don't have GCA so my rheumatogist submitted an authorization request and got Actemra approved for me. The approval authorized my rheumatologist to treat PMR with Actemra under the same guidelines used for GCA.

There is now another biologic that is approved for PMR. This biologic is called Kevzara (sarilumab).

Kevzara and Actemra are 2 different biologics but are in the same classification. The mechanism of action is basically the same.
https://www.ajmc.com/view/sarilumab-indication-expanded-to-include-polymyalgia-rheumatica

christopherc | @christopherc | Aug 30, 2023

In reply to @dadcue "The following link talks about a research study with Actemra (tocilizumab) for the treatment of PMR...." + (show)

Thanks for this additional information. It is very helpful. You have made a very meaningful contribution to the support
group.

DadCue | @dadcue | Aug 30, 2023

In reply to @christopherc "Thanks for this additional information. It is very helpful. You have made a very meaningful contribution..." + (show)

I don't wish to suggest that Actemra is a perfect solution for PMR/GCA. My rheumatologist didn't make any guarantees that Actemra would work. He just wanted me to try Actemra because he didn't want me to take prednisone for the rest of my life. I'm happy that I tried Actemra.

I think corticosteroid dependence and adrenal insufficiency due to a long term prednisone use was a significant part of my problem. Those symptoms took a long time to improve after I was able to taper off prednisone.

I don't know if Actemra will ever be discontinued. However, biologics in general have a tendency to stop working for the reason that is explained in following link.
https://www.verywellhealth.com/antibodies-to-biologics-4846279#:~:text=Because%20biologics%20are%20created%20using,different%20for%20each%20individual%20drug.