We Have Too Many Cortisol Receptors

[armymp]

Ok.. I went to my Psyciatrist (sp) the other day.. were I see a counselor at my school we are required to the the Doc ever so often. Anyway, it was amazing. I had never seen this doc before but he kept looking at me funny while we were talking, then he was like "Can I feel your legs and neck?" I was like "OK"? Then he sat back and was like "Have you ever been tested for something called Cushing's"? OMG.... I just looked at him and was like.. "If you only knew". I told him a little bit about my ordeal and you could tell he was kinda interested. He said that he saw some people with Cushing's while in med school and that they had made a wild discovery. He said that they found that some patients whose Cushing's tests all come back normal are false negative tests. He said that they have way too many cortisol receptors that take up the extra cortisol. He said that is why all of the tests come back normal, that there is actually way too much cortisol being produced but the extra receptors make the tests all come back normal.

 

Has anyone else heard this??? I think I may ask him where I can find the research about that.

[CarryMeSam]

wow, awesome info!!! definitely ask him and keep us posted!

[Koo]

I would definately like to see the research on this. Even if it is just one single paper. Why doesn't information like this get to the people who need it (like the docs that are running us into the ground with misdiagnoses). Maybe he will help you get to treatment for this!

 

Thanks! Hugs,

KRistin

[armymp]

I would definately like to see the research on this. Even if it is just one single paper. Why doesn't information like this get to the people who need it (like the docs that are running us into the ground with misdiagnoses). Maybe he will help you get to treatment for this!

 

Thanks! Hugs,

KRistin

 

 

I doubt that. He said he would love to but can't help me because he can't refer me. He's just a resident. Go figure. But maybe I can take this information and us it some how. Of course the school's website is down the past 3 days and I can't get his email address.

[fatnsassy]

Ooo,ooo,ooooo! Please do see if you can find a paper on that! It would make total sense to me as to why my testing was the way it was.

 

1. My percent free cortisol was really low. Like 1.9% or something similar. I'd have to look. Everyone should have more than that free, het my cortisol binding globulin was not high.

 

2. My IPSS results were weird. I definitely had sky high ACTH on my IPSS. It was 2,000 something, but my cortisol only went up to 22!??! Weird! You'd think with ACTH in the 2,000 range, I'd have cortisol into the hundreds! I've always thought this was weird, but never had an answer for it!

 

3. I had a VERY hard time catching highs! Yet, I had MANY symptoms of Cushing's. I ultimately proved it, and I'm doing well in recovery. I'm only on 10 mg. of hydrocortisone with no adrenals, and at times feel that is too much. Yet, I don't feel I have rest tissue.

 

Thanks so much for sharing this information with us, and I hope that doc can share an article about it! That would help SO MANY Cushing's patients. Many people have similar cases to mine, and this might be their issue as well!

 

Hugs,

Gracie

[Koo]

It might be good that he is a resident in a way. I'm sorry that you can't get a referral from him (can he talk to the doc that is over him and get his help?) However, this means that he should still be in contact with the professors and other residents. Maybe this study is still in progress or waiting for validation. Possibly we could put some of our docs in touch with the school. Are you going to continue to see him? If so I bet he will help you with referral.

 

Hugs,

Kristin

[armymp]

The bad thing is that they come and go so fast since they are residents. He will only be there for a year and we only get 2 to 4 appointments a year with them. I don't go back till Feb. but I am going to email him as soon as the website is back up. I hope he can help me get more info on this. I told my husband that I wonder what my PCP would say if I told him this.. prob that he this other doc has no clue what he is talking about. No... my PCP probably wouldn't even believe me. He doesn't believe a word that comes out of my mouth anyway, he would prob think I was making it up.

[zhen]

There's a drug in the pipeline that could help. Incyte is through phase II on a product labeled INCB13739 for type 2 diabetes. It works by inhibiting conversion of cortisone to cortisol by inhibiting 11-beta hydroxysteroid dehydrogenase.

 

Incyte

[MCF]

Some of us have too few receptors or receptors that aren't sensitive enough, so we produce excess cortisol. Receptor status is highly heritable, which certainly explains why we see so many families with affected members. Also, excess cortisol or use of steroids actually reduces the number of receptors a LOT, I learned when reading about topical steroid use, which means you have to overproduce because there aren't enough of them to deliver cortisol to target tissues.

 

There's a drug in the pipeline that could help. Incyte is through phase II on a product labeled INCB13739 for type 2 diabetes. It works by inhibiting conversion of cortisone to cortisol by inhibiting 11-beta hydroxysteroid dehydrogenase.

 

Incyte

 

Won't that increase inflammation, though, by causing additional CRH and ACTH release? I'm much more interested in getting my hands on Astressin or Antalarmin, or even mifepristone.

[missaf]

Mifepristone even makes me nervous. If you paralyze too many cells and their cortisol uptake, you're still going to run into the feedback loop resistances and it sounds lie your body will become an adrenaline junkie just to get through stressful situations.

[MCF]

Mifepristone even makes me nervous. If you paralyze too many cells and their cortisol uptake, you're still going to run into the feedback loop resistances and it sounds lie your body will become an adrenaline junkie just to get through stressful situations.

 

I hope there's a dose level where the dangers are minimized and benefits accrue. By blocking receptors, mifepristone supposedly upregulates how sensitive they are, and how many of them you have. That could mean you don't need to stay on it all the time or long term. Time will tell. For some reason, I'm someone for whom mini doses of drugs have both benefits and side effects, even at near homeopathic doses.

[fatnsassy]

There's a drug in the pipeline that could help. Incyte is through phase II on a product labeled INCB13739 for type 2 diabetes. It works by inhibiting conversion of cortisone to cortisol by inhibiting 11-beta hydroxysteroid dehydrogenase.

 

Incyte

 

 

If it's a type 2 diabetes drug, what would it do to you if you don't have type 2 diabetes, or any type diabetes? Mess up your insulin and make you hypoglycemic?

[zhen]

I think the alternate use and cost of mifaprisone will keep it out of reach.

 

There's a phase IIb report on INCB13739 at:

 

Phase IIB results

 

I was impressed enough to buy 1000 shares of Incyte because I believe this will lead to weight loss for type II's. The use in Cushing's, if any would be small compared with use for type II diabetes. I also called and asked how to enroll in phase III, but the answer to that was "not yet".

 

I hadn't read about ACTH causing inflammation. I'll look into that. It did cause ACTH rise, but feedback was maintained. Twelve weeks is not long enough to sort out side effects from that. I think ACTH can stimulate aldosterone release. If that happens, MR receptors need to be blocked too because aldosterone acts on heart muscle and artery walls to cause hypertrophy.

 

In pituitary cushing's, would this have any effect on ACTH anyway? The ACTH comes from the adenoma without regard to cortisol.

 

If it's a type 2 diabetes drug, what would it do to you if you don't have type 2 diabetes, or any type diabetes? Mess up your insulin and make you hypoglycemic?

 

It modulates cortisol by preventing cortisone > cortisol conversion by 11bsd1. It doesn't directly effect insulin secretion. By modulating cortisol, it treats metabolic resistance. That's a key feature of Cushing's. That's why I'm optimistic it has a place here.

[MCF]

Mifepristone is an old drug, RU 486, the morning after pill. It should be possible to buy it very cheaply, if one doesn't get the new patented one they're studying, Corlux. If I were fortunate enough to try it, I'd want microdosing.

 

CRH, more than ACTH is implicated in any chronic inflammatory condition you can name, from asthma to psoriasis, where the skin on biopsy is loaded with CRH and to a lesser degree, ACTH.

[lbeu12]

I don't have much to add, but I am VERY interested in this topic. I'm trying to figure out why and how I have such high midnight cortisol serum (total cortisol) but usually normal free cortisol urines and salava tests. I know it could have to do with CBG, but I keep hearing that if CBG is high, and my body is binding the free cortisol, then I it isn't negatively affecting my body. I disagree since my body is obviously showing the signs and symptoms of highs and lows. I don't know for sure if I have high CBG since it has never been tested. But the cortisol receptors are something I know nothing about.

 

And I know my Dad is in the process of being diagnosed with Psoriatic Arthritis (inflammation all over his body and many of the same signs and symptoms that I have - which are Cushing's related too). I don't know if maybe he actually has Cushing's like I might, or if I just happen to have a pituitary tumor, enlarged adrenal gland with nodules, and psoriatic arthritis like he might. But I just want to get answers...

 

Thanks for the post!

[missaf]

Cushing's is still Cushing's, even if you can't get high urinary free cortisols and salivaries. How are your 17 hydroxysteroids? A flip in your diurnal cycle is a huge key.

[lbeu12]

Cushing's is still Cushing's, even if you can't get high urinary free cortisols and salivaries. How are your 17 hydroxysteroids? A flip in your diurnal cycle is a huge key.

 

Missaf,

Thanks for your input...and the vote of confidence. I agree with you, but I don't have all the literature that I need. I definitely have a flip in my diurnal rhythm - seen at Cushie Camp. My doctor won't have me do midnight serums except with the PICC line, so I'm just turning in normal salivaries and urines. It is frustrating and making me second guess myself. But I know that many of you have only had high serums and moved on to surgery. I might have to switch and see Dr. F just because my body won't cooperate with the testing protocol of my current doctor...even though I do have tons of respect for him. I haven't had any 10 hr urines or 17 hydroxysteroids tested. But maybe that is the key for me...with Dr. F someday.

 

Any other suggestions or tips for me? Sorry for "stealing" this thread for a bit...but I can't wait to hear more info about all of these topics!

[Jo MacRaild]

Following on from the 17 hdxy's...heres an article Den sent me...that states different types of adrenal nodules /tumors do different things & produce non typical responses to testing & affect ufc spillage..

 

http://jcem.endojournals.org/cgi/content/full/94/8/2930

 

 

I'd be very interested in the receptor info. The zero ufc's we keep getting dont fit the clinical symptoms & way over the top steroid metabolites. Metyrapone is a cortisol blocker that works at 11betahydroxy..they tried it here..ended up in ICU..

[MelissaTX]

Facinating stuff folks. Thanks. I'm interested in any medical literature as well. If you post it here, I'll get email updates. If you post it in a new thread, I may not see it.

[sal]

I think it bolsters the childhood trauma theory. Our receptors are screwed up because they were taught from a young age to expect unusually high levels of stress. That fits with my childhood and teen years.

[missaf]

Aha! I remember that study! It talked about faulty development of the HPA and how the axis would be expecting more cortisol thanks to childhood trauma. This explains so much. That fits my childhood and teen years, too. But I also have the complications resulting from my dad's Agent Orange exposure and the signs and symptoms I was born with that Endos like Dr. F found interesting.

 

I think it bolsters the childhood trauma theory. Our receptors are screwed up because they were taught from a young age to expect unusually high levels of stress. That fits with my childhood and teen years.

[CarryMeSam]

it's a really good theory! I had a lot of childhood trauma of many types growing up so that doesn't surprise me.

[adriennebeth1]

I am 7 weeks post op.....I found out that I was full blown cushings and if my endo relied on urine test I would be dead or close. I had over a year of testing urine and had 1 high of 108......which is nothing. I hate when these doctors see normal urines and dismiss us......I had talked to my endo about an article about the receptors, she had read it too. I am trying to find it so I can post it.

 

Hugs, Adrienne

[MelissaTX]

Aha! I remember that study! It talked about faulty development of the HPA and how the axis would be expecting more cortisol thanks to childhood trauma. This explains so much. That fits my childhood and teen years, too. But I also have the complications resulting from my dad's Agent Orange exposure and the signs and symptoms I was born with that Endos like Dr. F found interesting.

 

Can you share what you know about the effects of agent orange affected veterans' descendants? Any medical articles? My father was in the marines and stationed in Vietnam twice during the war. He has reoccurring prostate cancer which is also linked to agent orange exposure.

[MelissaTX]

Can you share what you know about the effects of agent orange affected veterans' descendants? Any medical articles? My father was in the marines and stationed in Vietnam twice during the war. He has reoccurring prostate cancer which is also linked to agent orange exposure.

 

I guess I mean, do you know of any sources showing links between agent orange/dioxin and pituitary and adrenal cases? I found this: http://www.vva.org/veteran/1207/agent_orange_feature.htmland it mentions adrenal gland cancer. I had to stop and post. I'm reading and researching more.