Cortisol on the brain

[hardasnails1973]

What are the specific areas of the brain that are damaged from excessive exposure to cortisol and what are the ramifications of this on a persons behavior. Would damaging these areas cause person to over react a normal stress response? Would excessive coritsol tend to make a person feel more insecure about them selves and create an environment of lack of self confidence. Could prolong effect on cortisol cause alterations in calcium metabolism to where this could start to effect the mouth, gums, teeth enamel as well as causing abnormal curvatures in the spine due to bone demineralization. Cortisol is a nasty thing, but I would love to understand more of its action and how it can affect a person’s behavior and mental state.

If a person that is experiencing high cortisol at night before bed time be better off with melatonin or PS (phosphodytial serosine)?

[Shaolin]

Cortisol can do amazing things to someones brain. I will tell you what i suffered from from unecessary exogenous cortisol supplementation if you are interested. Its pretty scary though.

[hardasnails1973]

@Shaolin 497 wrote:

Cortisol can do amazing things to someones brain. I will tell you what i suffered from from unecessary exogenous cortisol supplementation if you are interested. Its pretty scary though.

shaolin
I would like to know the interactions with neurotransmiters and also phyiscal effects you were experiencing due to excessive cortisol production. How much cortisol where you on to experience these side effects?

[DrMariano2]

@hardasnails1973 469 wrote:

What are the specific areas of the brain that are damaged from excessive exposure to cortisol and what are the ramifications of this on a persons behavior. Would damaging these areas cause person to over react a normal stress response? Would excessive coritsol tend to make a person feel more insecure about them selves and create an environment of lack of self confidence. Could prolong effect on cortisol cause alterations in calcium metabolism to where this could start to effect the mouth, gums, teeth enamel as well as causing abnormal curvatures in the spine due to bone demineralization. Cortisol is a nasty thing, but I would love to understand more of its action and how it can affect a person’s behavior and mental state.

If a person that is experiencing high cortisol at night before bed time be better off with melatonin or PS (phosphodytial serosine)?

The most studied area regarding “damage” from high cortisol levels is the hippocampus. The hippocampus is a central area for memory storage.

The problem I have is that the studies I see are primarily in vivo studies on brain cells in petri dishes exposed to supraphysiologic levels of cortisol. Of course, in this scenario, damage is going to occur.

In real life, in all the years I have practiced, I only see low or normal levels of cortisol in patients that seek help.

I truly question whether or not physiologic levels of cortisol cause any damage. If anything, from what I see, it is the loss of glucocorticoid receptors and the loss of cortisol production in mood and psychotic disorders that leads to dysfunction.

Glucocorticoid receptors (the receptors for cortisol) are distributed throughout the brain. There is loss of such receptors in mental illness (psychotic and mood (which includes anxiety disorders). Yet, the only volume loss is seen in the hippocampus. Why is this the only area of “damage”? I think there are other factors involved – such as pro-inflammatory cytokine mediated changes – that are more likely causes of volume or cell loss. Notably, there is no good evidence that there is actually cell loss in the hippocampus, only volume loss. For example, if there is loss of myelination, there would be volume loss and slower signal processing, but not necessarily cell loss.

Cortisol is very important for brain function. Under stress, for example, cortisol allows the amygdala to not be distracted by emotionally distracting content, in order to allow the brain to focus better in task performance. Cortisol allows the brain to not be disabled by emotionally traumatizing memories. Cortisol also helps reduce damage from pro-inflammatory changes, helping reduce excessive immune system activity.

The most important point I would emphasize is that I don’t see supraphysiologic levels of cortisol in ill people (outside of Cushing’s syndrome). Rather, in real life, it is low cortisol that is the problem.

When there is high cortisol, it is always a response to high norepinephrine signaling. It is the high norepinephrine signaling and its ramifications (e.g. insulin resistance, increased histamine, increase pro-inflammatory cytokine signaling), that causes the problems, including insomnia.

Glucocorticoid receptors in the brain with areas with higher receptor density indicated by +++:

Neocortex
Frontal Lobes
Prefrontal cortex
Temporal Lobes
Parietal Lobes
Occipital Lobes
Corpus Callosum

Limbic System
Amygdala +++
Stria Terminalis
Bed Nucleus of the Stria Terminalis +++
Nucleus Accumbens
Basal Nucleus of Meynert
Hippocampus +++
Basal Ganglia +++
Caudate
Putamen
Globus Pallidus

Diencephalon
Thalamus
Epithalamus
Pineal Gland
Subthalamus
Hypothalamus +++
Paraventricular Nucleus +++
Arcuate Nucleus +++
Pituitary

Brainstem
Midbrain
Tectum
Tegmentum
Substantia Nigra
Cerebellum +++
Pons
Locus Ceruleus +++
Medulla Oblongata

Spinal Cord

—-

By the way, I would love to see discussion that show the opposite of what I see. It is just that I don’t see high cortisol levels in real life (by this, I mean supraphysiologic levels).

[hardasnails1973]

I can concur 100% in the majority of people walking through the door it is normal or low levels. More so we see fluctuation of levels through out the day time as typical scenerio.

I had one person whose cortisol levels where elevated. His previous dr tried every thing to get them down would not budge. Further examination that the thyroid was low. Treatment of thyroid hormone actually reduced his cortisol levels back down to normal level.

Now the question reminds is that would correcting the thyroid condition possible undercover a hidden adrenal problem. After 8 weeks on the thyroid serum cortisol am levels dropped from 22 down to 13.5. He is also starting to notice fatigue and sluggishness as well so to rule this out a cortisol saliva test would be performed. From the data we will see if adrenal support is need.

I was familar with cortisol can cause brain damage but just did not know what area.

My fiancee has elevated cortisol levels in the saliva test and sleeping issue which are common symptoms of high cortisol levels. She has really high levels at night time and it is my understanding the Phosphodyital serosine is need to help modulate these levels. Her memory is horrible and was wondering if the PS could help to restore the potential damage that has been done. Be glad to post her saliva test.

I believe the elevated cortisol levels are the reason for her degeneration of her neck and spine resulting in typical “runners positon with neck forward” Her body is already in the position to flee in any dangerous situation. She also complains of pain over the kidney area exactly where the adrenals are located. Also the trigger point right on the scapular border is always constantly tender.

I do not know if its a correlation or not but when I suspect adrenal imbalances when I apply pressure to the middle of gastrocnemius the person jumps out of their skin. These people adrenal reports also come up in balanced as well.

[DrMariano2]

@hardasnails1973 522 wrote:

I can concur 100% in the majority of people walking through the door it is normal or low levels. More so we see fluctuation of levels through out the day time as typical scenerio.

I had one person whose cortisol levels where elevated. His previous dr tried every thing to get them down would not budge. Further examination that the thyroid was low. Treatment of thyroid hormone actually reduced his cortisol levels back down to normal level.

Now the question reminds is that would correcting the thyroid condition possible undercover a hidden adrenal problem. After 8 weeks on the thyroid serum cortisol am levels dropped from 22 down to 13.5. He is also starting to notice fatigue and sluggishness as well so to rule this out a cortisol saliva test would be performed. From the data we will see if adrenal support is need.

I was familar with cortisol can cause brain damage but just did not know what area.

My fiancee has elevated cortisol levels in the saliva test and sleeping issue which are common symptoms of high cortisol levels. She has really high levels at night time and it is my understanding the Phosphodyital serosine is need to help modulate these levels. Her memory is horrible and was wondering if the PS could help to restore the potential damage that has been done. Be glad to post her saliva test.

I believe the elevated cortisol levels are the reason for her degeneration of her neck and spine resulting in typical “runners positon with neck forward” Her body is already in the position to flee in any dangerous situation. She also complains of pain over the kidney area exactly where the adrenals are located. Also the trigger point right on the scapular border is always constantly tender.

I do not know if its a correlation or not but when I suspect adrenal imbalances when I apply pressure to the middle of gastrocnemius the person jumps out of their skin. These people adrenal reports also come up in balanced as well.

How elevated was the AM Cortisol of that person initially? 30? 40?

An AM Cortisol of 22 is pretty normal.

If the addition of thyroid hormone to treatment, even if thyroid hormone is deficient, drops AM Cortisol from 22 down to 13.4, then the thyroid hormone may be the cause of the adrenal problem. I would certainly look for other signs prior to thyroid treatment of HPA Axis dysregulation before considering adrenal support. Diagnosing an adrenal problem by thyroid hormone treatment is problematic because the treatment may be the cause of the problem.

What was the initial Total T4? If the initial Total T4 is > 8, I would not add thyroid hormone initially. If there are signs consistent hypothyroidism, then I would first suspect a metabolic-nutritional problem or other signaling problem to correct first, particularly with an AM Cortisol of 22. This would be the cause of a low Free T3, or T4 to T3 conversion problems. A Total T4 > 8 indicates adequate thyroid hormone is being produced by the thyroid. It is a non-thyroid illness that is causing the problem. I would assess for the non-thyroid illness first.

—-

When a person has insomnia and high cortisol levels at night, the problem is excessive production of norepinephrine. Cortisol production is a downstream response to elevated norepinephrine signaling. If Cortisol wasn’t high, then the person would have more overt anxiety or irritability or other mood symptoms, not just insomnia. Cortisol helps prevent norepinephrine from going up even higher.

Cortisol is the response signal to stress. It is not the problem. Stress is. Or rather, excessive norepinephrine – the primary signal for stress – is the problem.

Again, how elevated is the cortisol? When you say high, how high is high? 30? 50? 60? Is it a clearly supraphysiologic level? Or is it a normal elevated level in response to stress?

The usual cortisol level curve found on lab tests – where cortisol is high in the morning and low in the evening ASSUME a person is non-stressed and is at rest. These time curves are changed when a person is under stress. Just have a person exercise strenuously with heavy weights just before doing a cortisol test. See how high a normal cortisol can go from this stress. The AM Cortisol of a person who weight-lifted heavily the night before can easily be 30+. I regard this level as NORMAL.

—

KYPHOSIS:

Kyphosis is a forward slouching of the spine may have many causes. I would consider other causes first before cortisol.

Causes may include:

Growth Hormone Deficiency – such as from aging
Nutritional Kyphosis – such as from Vitamin D deficiency
Postural Kyphosis – from slouching.
Hereditary Kyphosis
Congenital Kyphosis

—

Pain in the kidney area is most often associated with the kidneys. The kidney has a capsule which if stretched (such as from infection and inflammation) causes pain.

The adrenal glands can enlarge or become hypertrophic in response to stress. This is generally not associated with pain.

[shan_e_wilson]

Great post hardasnails1973! Describes me to the t..haha.

It drives me nuts that I feel my heart pumping all the time. I really try not to think so much..but I know I constantly do it. It’s like I can’t rest my mind. To not just “think”, I will admit..is hard to do. I’m not sure if anyone else has this issue, but I know my mind goes a mile a minute.

The questions you asked here on this post and how Dr. Mariano responded is great information to understand! I find it interesting how high norepinephrine affects ones body.

3 mgs of the time release Melatonin use to work good for me for sleeping, but now it has lost it’s affect it once had on me. Doesn’t work as good now. I know I need more sleep, but it’s hard to just fall asleep.

[hardasnails1973]

It is also noted that the higher the stress level and cortisol more resistant or faster the metabolism of the medicine occurs. Some people can take an advil for PMS other people have to take a percocet which is usually sign that there hormonal system is completely out of balance. This ocurrance usually has to do with excessive estrodial to low progesterone that may affect the thyroid signaling due to elevated TBG. Even though ones thyroid labs are optimal if the signaling of the thyroid is disrupted then hypothyroid symptoms could be apparent. Many time I see this in practice to where women’s thyroid look functional but they still suffer symptoms of low thyroid. Upon further investigation it is found that they have low progesterone/e2 ratio which once corrected over time the thyroid symptoms tend to decrease. Symptoms will only decrease provided that there is also optimal functioning of the adrenals and proper ferritin levels. One also needs to look at testosterone in the women because this can cause PCOS which can also have similar symptoms as low thyroid such as hair loss. When PCOS is suspected when women are placed on DIM, progesterone, iodoral, with spearment tea (Dr Jonathon Wright) it is found to reduce androgen signifcantly. We are using this therapy on a female patient right now as she has very high Testosterone and low SHBG levels.

[DrMariano2]

@shan_e_wilson 644 wrote:

Great post hardasnails1973! Describes me to the t..haha.

It drives me nuts that I feel my heart pumping all the time. I really try not to think so much..but I know I constantly do it. It’s like I can’t rest my mind. To not just “think”, I will admit..is hard to do. I’m not sure if anyone else has this issue, but I know my mind goes a mile a minute.

The questions you asked here on this post and how Dr. Mariano responded is great information to understand! I find it interesting how high norepinephrine affects ones body.

3 mgs of the time release Melatonin use to work good for me for sleeping, but now it has lost it’s affect it once had on me. Doesn’t work as good now. I know I need more sleep, but it’s hard to just fall asleep.

The subjective sensation of racing thoughts or the overt presence of rapid or pressured speech is associated with excessive norepinephrine signaling.

This happens, for example, in the manic episodes of bipolar disorder or when a person overdrives their brain by using too high of a dose of a stimulant. Bipolar disorder is an example of condition driven by high norepinephrine signaling, hypothalamic-pituitary-adrenal dysregulation, and hypothyroidism (clinical or subclinical or cellular).

Insomnia occurs when excessive norepinephrine. Melatonin is working but is overruled by norepinephrine – the primary signal for distress, stress, emergencies, survival mode, etc. Once the adrenals also develop suboptimal cortisol signaling, Melatonin, which reduces adrenal function as one of its actions, makes the situation worse at doses over 1 mg a night. The lower cortisol production from Melatonin worsens HPA axis dysregulation, resulting in higher norepinephrine signaling (Cortisol helps prevent excessive norepinephrine signaling).

The sensation of the heart pumping is also associated with excessive norepinephrine signaling, particularly when HPA axis dysregulation occurs and cortisol production is unable to match norepinephrine signaling.

Knocking down norepinephrine is difficult, particularly when it is a compensatory action for impaired energy production in the rest of the system (e.g. hypothyroidism, nutritional deficiencies, HPA Axis dysregulation, etc.). The mind is in survival mode under these circumstances. Reducing norepinephrine is like telling the mind it’s going to die. Thus, it may react against sedatives, for example, causing insomnia instead. Many times, particularly in psychiatry in the treatment of mental illness, multiple medications with different mechanisms of action have to be used to pull it down – its like trying to control a wild bull that’s taking one for a ride.

[shan_e_wilson]

Wow..that is interesting what you say Dr. Mariano. My body is not the same as other people’s I find most of the time. When I have a surgery or when I have bad pain from menstrual cycles, the only thing that works for me is Percocet or Dilaudid, which I know aren’t’ great for you. I have always since I can remember had to take stronger medication or higher doses, because what normally works for most..does not even phase me the bit least.

I always learn so much from hardasnails1973, and since I came onto the discussion boards here, I have learned and am continuing learning from you Dr. Mariano and from other people who post. I appreciate your information you shared with me. It really does make since when you think about it.

[DrMariano2]

@shan_e_wilson 661 wrote:

Wow..that is interesting what you say Dr. Mariano. My body is not the same as other people’s I find most of the time. When I have a surgery or when I have bad pain from menstrual cycles, the only thing that works for me is Percocet or Dilaudid, which I know aren’t’ great for you. I have always since I can remember had to take stronger medication or higher doses, because what normally works for most..does not even phase me the bit least.

When norepinephrine is set on high, the brain allows all the sensory input to be more sensitive. This is a defensive position. The brain is shifted to a more aware state.

This, however, can also have the negative effect of making a person overly sensitive to noise, light, pain, etc.

Opiate pain medications stimulate opiate receptors. In doing so, they also end up increasing dopamine signaling. Dopamine is one of the control signals for stress / norepinephrine signaling. This is one way opiates can reduce blood pressure, for example, since norepinephrine is a signal for increasing blood pressure.

I would wonder if there is an impaired connection between the opiate and dopamine signaling, when it comes to the need for higher opiate pain medication dosing in some people.

A negative in some people of using an opiate pain medication is that opiates also increase brain mast cell histamine signaling and depress adrenal cortisol signaling and increase pro-inflammatory cytokine signaling from brain microglia, and end up increasing norepinephrine. Thus, in some people, opiates can create a central pain syndrome or destabilize mood – for example, causing mania or paranoid delusions. Of course, this doesn’t happen in the vast majority of people. But it occurs in some. Thus physicians need to be aware of this effect in some patients.

[Shaolin]

Thanks Dr. M for reestablishing in my mind the damage noradrenaline did to me.

It all started from finasteride. when i was just 24 yrs old

This drug lowered my HPG and testosterone output with the following years (despite discontinuine use). I tried to overcompensate by doing exercise and lifting weights. Ended up after a few months overtrained and had to stay in bed for like a year and a half to get better. Noradrenaline levels where super sky rocketing for all this time. The worst time of my life.

Symptoms-

exhaustion and complete weakness
irritability
Insomnia (major one)
couldnt listen to any noises
couldnt stand bright light
feelings of heavy legs and leg inflammation (especially quadriceps weighed like a ton each)
a bunch of other weird ones like discoordination in walking (as much as i could walk), breathing difficulties, headaches, nausea, feeling of tightness at the back of my neck and lower occipital region
massive backache
fast pulse when standing (that went on for 8 months)
prolonged time for pulse rate to return to basal level after swimming (the only exercise i could do, coz walking was a major problem back then so i drove every 3-4 days to the sea and tried to swim but it was all in vain i was so dead and this didnt help)

and a bunch of other symptoms

i learned about the dreadful noradrenaline potentials from you, all that time i just thought i was overtrained and couldnt explain what was wrong, didnt know of adrenal fatigue or HPA axis dysregulation.

That time was hell

Now i am a bit better but not more than 30% than before, i still have the other mystery to solve, why are my testicles shrinking for the last two years continuously (and hurting). I had this situation when i first took finasteride but something retriggered the whole mechanism now, its either a low 5-ar II genetic encoding function or something in my Andr. receptors or some other loop that controlls 5-ar II production and dht, really dont know, great mystery, great mess….

Great forum by the way, thanks for educating patients …

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