HPA-Axis Dysfunction - Help!

[Astolfo]

Do we have any success report with glucocorticoids?

At the time when I was using fluoxetine, I was also being use triamcinolone acetonide for a few days. It's a synthetic glucocorticoid. And its be possible to it had interacted with fluoxetine.

The cytochrome P450 3A4 (CYP3A4) system metabolizes nearly half of all hepatically cleared drugs, and can result in clinically relevant drug interactions including elevating serum levels of exogenous steroids . Fluoxetine is an example of a CYP3A4 inhibitor in common use, and has been associated with elevated serum concentrations of antipsychotics and warfarin, but has no prior documentation of effecting metabolism of glucocorticoids . While metabolism of glucocorticoids and their long-term side effects may be managed in patients with a clear history of glucocorticoid use, persistent elevation of injectable steroids as a result of the CYP3A4 system may be overlooked and result in complications .

I had took a hormone panel test a few months ago. My cortisol was 8.72 (Ref: 8.72-22.4). I couldn't believe this as I had a serious anxiety problem before the pssd. It must had been at least 20 if I hadn't ever been used an antidepressant.
I have nothing to do to prove what the exact thing is wrong in my body. But this is the only exception till this time I think.

Zero response to coffee (actually it makes me really sleepy), chronic fatique, some sort of hypoglycemia symptoms etc.

Glucocorticoid alters 5-ht1a receptors:

Transcriptional regulation of the 5-HT1A receptor: implications for mental illness

Differential transcriptional regulation of 5-HT1A autoreceptors versus heteroreceptors is partly dictated by developmental and regional distribution of Htr1a transcriptional factors and alterations in regulators such as glucocorticoids. Thus, Pet-1 is raphe-specific, while Freud-2 is not detected in raphe cells and thus specifically regulates 5-HT1A heteroreceptors. Similarly, high- and low-affinity glucocorticoid receptors (mineralocorticoid receptor, MR, and glucocorticoid receptor, GR, respectively) are enriched in hippocampus compared with raphe and are critical for stress- or glucocorticoid-induced downregulation of hippocampal 5-HT1A receptors [40,71,87–92]. Consistent with the importance of negative regulation of 5-HT1A heteroreceptors by glucocorticoids, an inverse correlation between glucocorticoid levels and hippocampal and amygdala but not raphe 5-HT1A receptor levels is seen in anxiety disorder patients [93]. With elevated glucocorticoid conditions, such as in chronic mild stress or sleep deprivation [94,95], GR appears to repress 5-HT1A autoreceptors [96]. Glucocorticoids can also uncouple 5-HT1A autoreceptors by reducing GIRK2 RNA levels [29]. Paradoxically, over-expression of MR or GR in the mouse forebrain increases 5-HT1A heteroreceptor expression (possibly via suppression of glucocorticoids), which was associated with an anti-anxiety/anti-depressed phenotype and increased SSRI responsiveness, respectively [97,98]. Thus, chronic life stress may dysregulate the 5-HT system by reducing 5-HT1A heteroreceptor expression and increase susceptibility to mental illness (figure 1).

Model for Htr1a dysregulation in human anxiety and depression. Shown is a model of differential Htr1a regulation in pre-synaptic raphe 5-HT neurons projecting to post-synaptic neurons in target tissues involved in mood and affect, such as prefrontal cortex, hippocampus, amygdala or hypothalamus. Pre-synaptic 5-HT1A autoreceptors (v) negatively regulate 5-HT firing neuronal activity and regulate the release of 5-HT (dots) and activation of post-synaptic 5-HT1A heteroreceptors. In normal subjects, the set point for raphe firing frequency is determined in part by the density of 5-HT1A autoreceptors that is restrained by repression at the rs6295 C(-1019) allele (bar); 5-HT1A heteroreceptors, especially in cortex appear to be increased by enhancer activity at the C(-1019) allele (arrow). In anxiety, the combination of genetic (rs6295 G(-1019) allele) and environmental (life stress) glucocorticoid-mediated repression of the 5-HT1A promoter leads to a stronger decrease in 5-HT1A heteroreceptors in glucocorticoid-sensitive tissues, such as hippocampus and prefrontal cortex, and to a lesser extent the raphe nucleus; anxiety subjects appear to compensate for the de-repression of 5-HT1A autoreceptors in the raphe. In depression, the combination of G(-1019) allele and stress promote reductions in post-synaptic 5-HT1A heteroreceptors; however, pre-synaptic 5-HT1A autoreceptors become upregulated due to the lack of Deaf1 repression at the G(-1019) allele, leading to reduced 5-HT release, and compensatory partial upregulation of 5-HT1A heteroreceptors. In this model, antidepressants act mainly at heteroreceptors or other post-synaptic processes for anti-anxiety actions, while they also act to desensitize pre-synaptic sites to mediate antidepressant actions.

Steroid dementia syndrome - Wikipedia:

Steroid dementia syndrome describes the signs and symptoms of hippocampal and prefrontal cortical dysfunction, such as deficits in memory, attention, and executive function, induced by glucocorticoids.[1] Dementia-like symptoms have been found in some individuals who have been exposed to glucocorticoid medication, often dispensed in the form of asthma, arthritis, and anti-inflammatory steroid medications. The condition reverses, but not always completely, within months after steroid treatment is stopped.[2]

Signs and symptoms
Cognitive symptoms from steroids appear within the first few weeks of treatment, appear to be dose dependent, and may or may not be accompanied by steroid psychosis or other Cushing's-type symptoms.[4]

The symptoms include deficits in

verbal and non-verbal memory
working memory
attention
sustained concentration
executive function
psychomotor speed
academic or occupational performance.
These symptoms have been shown to improve within months to a year after discontinuing glucocorticoid medication, but residual impairments following prolonged steroid use can remain.[3]

GR dysfunction --> hpa-axis dysregulation
"" ---> 5-ht1a receptor imbalance ---> cognitive impairment

Mifepristone (ru486) is able to fix hpa-axis dysregulation (both hyper and hypo cortisolism). I had read somethings about this on longecity.com before. I feel like I just coming from behind, though. I hope I'm not just repeating all the things already been said in this forum before.


And, this is the topic which I opened at an another forum.

How can I solve my adrenal insufficiency? Do you think it's because of the excessively upregulated glucocorticoid receptors?

 

[Astolfo]

Bump

 

[Astolfo]

Cognitive side effects are really bad. Really help!

I lost my brain. It’s ******* gone.

 

[Astolfo]

Bump

 

[Momado965]

Why isnt anyone replying to your thread?

 

[Memento]

Does fasting Make your symptoms worse? Have you tried ketogenic diet?

 

[Beefcake]

Do we have any success report with glucocorticoids?

At the time when I was using fluoxetine, I was also being use triamcinolone acetonide for a few days. It's a synthetic glucocorticoid. And its be possible to it had interacted with fluoxetine.



I had took a hormone panel test a few months ago. My cortisol was 8.72 (Ref: 8.72-22.4). I couldn't believe this as I had a serious anxiety problem before the pssd. It must had been at least 20 if I hadn't ever been used an antidepressant.
I have nothing to do to prove what the exact thing is wrong in my body. But this is the only exception till this time I think.

Zero response to coffee (actually it makes me really sleepy), chronic fatique, some sort of hypoglycemia symptoms etc.

Glucocorticoid alters 5-ht1a receptors:

Transcriptional regulation of the 5-HT1A receptor: implications for mental illness







Steroid dementia syndrome - Wikipedia:






GR dysfunction --> hpa-axis dysregulation
"" ---> 5-ht1a receptor imbalance ---> cognitive impairment

Mifepristone (ru486) is able to fix hpa-axis dysregulation (both hyper and hypo cortisolism). I had read somethings about this on longecity.com before. I feel like I just coming from behind, though. I hope I'm not just repeating all the things already been said in this forum before.


And, this is the topic which I opened at an another forum.

How can I solve my adrenal insufficiency? Do you think it's because of the excessively upregulated glucocorticoid receptors?

Have you investigated vitamin and mineral deficiencies through blood testing?
If so please share your results.

 

[Astolfo]

Does fasting Make your symptoms worse? Have you tried ketogenic diet?

Tried for 1,5 week. Didn’t do anything.

Have you investigated vitamin and mineral deficiencies through blood testing?
If so please share your results.

I didn’t check my vitamin or mineral levels. I had tried mag oxide, b complex, C though.

Why isnt anyone replying to your thread?

I don’t really know. I’m asking this question to myself since a long time.

 

[Beefcake]

Tried for 1,5 week. Didn’t do anything.



I didn’t check my vitamin or mineral levels. I had tried mag oxide, b complex, C though.




I don’t really know. I’m asking this question to myself since a long time.

You have to get a full blood work of vitamins and minerals. As many asy you can. A deficiency can easily give you an under active pituitary. Happened to me ones.

 

[Nnanuu]

Don't try to figure this out by yourself. It's a waste of time if you are already cognitively impaired.
If you have PSSD try to emulate things which have cured people.
If you have more problems then that use some established system at least.
Whatever you believe in:
- Ray peat approach
- Fasting/Breuss
- Mineral balancing
- Homeopathy
- Whatever

I don't know.
But reading studies and guessing around without tests - it's a waste of time and energy.

Good luck!

 

[Astolfo]

You have to get a full blood work of vitamins and minerals. As many asy you can. A deficiency can easily give you an under active pituitary. Happened to me ones.

I will try to get one test. I have some economical issues lately.

Don't try to figure this out by yourself. It's a waste of time if you are already cognitively impaired.
If you have PSSD try to emulate things which have cured people.
If you have more problems then that use some established system at least.
Whatever you believe in:
- Ray peat approach
- Fasting/Breuss
- Mineral balancing
- Homeopathy
- Whatever

I don't know.
But reading studies and guessing around without tests - it's a waste of time and energy.

Good luck!

Yeah, thanks. It’s so much true that I can’t do anything by myself while I’m this much cognitively impaired.

- Ketogenic diet (1,5 week)
- Reducing Fat, especially PUFA
- B complex, K2, C, NAC 600 mg, Cyproheptadine 0.5 mg/1 mg/2 mg/4 mg

4 mg cypro made me terrible btw. Severe heart palpitations, visual disturbances, hypoglycemia etc. I guess it decreased my already nonexistent cortisol.

- Orange juice, coffee

Orange juice gives me heart palpitations and agitation.

Coffee does nothing. It makes me even more sleepy.


I don’t know how to fix my adrenal issues. I don’t even know if this could be possible that low cortisol gave me dementia, motor dysfunctions, myoclonic jerks.

I need to know what to do know.

 

[Nnanuu]

You could also put your trust into a (non-medical) practitioner. Talk to some and see what they think. Choose the one who optimally has already cured a case like you.
Get help.

Good luck!

 

[magnesiumania]

Sounds horrible. Im afraid i can't help or give any advice except that i suggest you take it as learning no matter how hard it feels. Im severly cognitivly impaired myself and i miss being able to use my brain so much.....I think biology has more potential for failiure in our modern times, with non-native EMF and all sorts of disturbances. Anyway, good luck!

You may wanna look into the Root Cause Protocol disigned by Morley Robbins. I think copper is important for brain homeostasis as our astrocytes (that basically regulate how our neurons commonucate) are driven by COPPER (which is what Morley's protocol is all about)

 

[LUH 3417]

Sounds horrible. Im afraid i can't help or give any advice except that i suggest you take it as learning no matter how hard it feels. Im severly cognitivly impaired myself and i miss being able to use my brain so much.....I think biology has more potential for failiure in our modern times, with non-native EMF and all sorts of disturbances. Anyway, good luck!

You may wanna look into the Root Cause Protocol disigned by Morley Robbins. I think copper is important for brain homeostasis as our astrocytes (that basically regulate how our neurons commonucate) are driven by COPPER (which is what Morley's protocol is all about)

Looks interesting. Have you tried it?

 

[LUH 3417]

Sounds horrible. Im afraid i can't help or give any advice except that i suggest you take it as learning no matter how hard it feels. Im severly cognitivly impaired myself and i miss being able to use my brain so much.....I think biology has more potential for failiure in our modern times, with non-native EMF and all sorts of disturbances. Anyway, good luck!

You may wanna look into the Root Cause Protocol disigned by Morley Robbins. I think copper is important for brain homeostasis as our astrocytes (that basically regulate how our neurons commonucate) are driven by COPPER (which is what Morley's protocol is all about)

They seem like supplement kits with stuff like cod liver oil. Plus a lot of the products have a bunch of fillers. I’m weary.

 

[magnesiumania]

Im basically doing the RCP with a little Peaty twist or smth....

Nothing wrong with CLO really (or at least not the brands recommended) Do you worry about the small percentage of PUFA? Cod liver oil has a bunchload of RETINOL which basically make ceruloplasmin to support copper/iron metabolism.

You can avoid supplements with fillers.... liquid magnesium etc...

 

[LUH 3417]

Im basically doing the RCP with a little Peaty twist or smth....

Nothing wrong with CLO really (or at least not the brands recommended) Do you worry about the small percentage of PUFA? Cod liver oil has a bunchload of RETINOL which basically make ceruloplasmin to support copper/iron metabolism.

You can avoid supplements with fillers.... liquid magnesium etc...

Honestly I’m just getting really tired of trying different supplement protocols and the idea of relying on supplements. It’s a financial strain as well as a mental burden. I feel like I’m not giving my body a chance. Do you notice many positive changes?

 

[magnesiumania]

Hmm its been a journey with a lot of content. But generally ive had a healing experience. Now that said i happen to have my brain destroyed by glutamate. About a year ago i experienced being poisoned. Ever since then ive been very sensitive to glutamate but i didnt realize before i actually supplemented glutamine, only to exerpience horrendous excitotoxicity that is STILL going on (3 months since i did glutamine supplementation). I mean magnesium used to give me a great boost but now it simply dont work anymore and im convinced hugh neuronal structures have just died/deleted themselves/apoptotic death.

So at the moment i dont feel the protocol does too much...although it may be the best thing for me, im just kinda beyond repair (trying to avoid "learned helplessness" so lets say thats not entirly true...