From time to time, I see patients with dysautonomia – where there is a greater than expected sympathetic nervous system response to a stress such as changing body positions, etc. causing a person to have palpitations – the sensation the heart is racing or excessively contracting.

When a person has a prolonged episode of illness, such as this, on of the problems to assess for is the presence of one or more positive feedback signaling loops which self-perpetuate the illness, and result in higher than expected signaling. From my point of view, the body and mind (which are the same thing from a neuroscience perspective) is a colony of cells arranged as a fluid network. Controlling signal transmission is usually done via negative feedback loops. The problem is that there are situations – such as diabetes – when the control of signaling involves positive feedback loops. Positive feedback loops lead to illness.

Another problem occurs when one doesn’t take into account all of the signaling interactions that are possible with a single intervention. Unexpected interactions may then occur, exacerbating or causing a problem. The mind and body’s signals tend to have numerous actions. It is the sum of these actions that determines the resulting behavior.

Hydrocortisone, when doing adrenal support, is suppose to make up for the missing hydrocortisone the adrenal glands should be making in response to a certain level of stress. However, there are potential problems when one adds hydrocortisone to one’s system.

For one, Hydrocortisone alone is an incomplete treatment. The adrenal glands can have upwards of 150 different signaling products made in response to stress/norepinephrine and ACTH signaling. Adding Hydrocortisone alone may replace what should have been made. But it also suppresses adrenocortical production of the other signals. This can result in a deficit of pregnenolone, progesterone, DHEA, possibly aldosterone, and lower testosterone and estrogen production, etc. etc. These have important functions. Reducing their production further can cause significant problems including anxiety, increase stress/norepinephrine, dizziness, loss of energy, etc. – the opposite of the intended effect. When one adrenal hormone is replaced, then all the others have to also be considered for replacement. This means, in a man, considering at the very least adding DHEA and pregnenolone to avoid signaling deficits or help address the subsequent signaling deficits that treatment with hydrocortisone can cause.

Hydrocortisone is also a signal to increase gastric acid production. In some people this results in acid reflux disease or gastritis. This in turn can lead to over-activation of the innate immune system cells and a large increase in inflammatory cytokine signaling. This can lead to a large increase in sympathetic nervous system signaling – priming the pump so to speak for dysautonomia. An overactivated innate immune system can prime the adaptive immune system leading to allergies, food allergies, etc.

In the beginning, before all these problems started, the most important question to ask is: Why was adrenal function impaired in the first place? Secondly, why is reverse T3 so high? Rather than immediately start an adrenal support treatment using hydrocortisone, which although it initially may help, in the end is an incomplete treatment, which can in the long run cause problems, one has to consider what is the cause of the problem in the first place. Is it a mental illness, nervous system problem? Is it an immune system problem? If there is an immune system problem, is there an infection? Is it an endocrine problem? Is it a nutrient or metabolic problem? These days, I prefer to try targeting the cause of adrenal dysregulation first before considering adding hydrocortisone. This line of treatment actually works better since treatment with hydrocortisone without considering the underlying causes is at most a bandage treatment which often never gets the person well.

Even before dysautonomia started, there may have been underlying, unaddressed problems, that were already priming the pump. There may already have been elevated norepinephrine signaling. Note that lab testing for catecholamines have to be re-calibrated to reflect behavior, not cancer, in order to determine if a level is high. That is usually what is not done thus high norepinephrine levels are often missed.

Because various signals can have good and bad effects, it is important to understand how they can cause bad effects and control for them in order to obtain the desired effect.

For example, even if a person is hypothyroid, if there is adrenal dysregulation or excessive inflammatory cytokine signaling, adding thyroid hormone can worsen both. The causes of these two conditions may have to be addressed first.

Adding testosterone to a system can exacerbate adrenal dysregulation by itself. Testosterone suppresses ACTH signaling and directly – independent of ACTH – suppresses adrenal cortex hormone production. The injection of testosterone can result in large peaks of testosterone, unlike the relatively flat levels achieved with transdermal testosterone. The peak blood levels may cause problems in some individuals – including even impaired libido. The excessive production of estradiol can increase norepinephrine signaling excessively either directly or in compensatory response to lower free thyroid levels caused by estrogen induction of thyroid binding globulin production. Estrogens can also increase inflammatory cytokine signaling, causing further downstream problems unless these are balanced by anti-inflammatory factors.

Whenever someone tells me they have a “good diet”, I often find a poor diet. Note that modern diets tend to be nutrient poor. A variety of nutrients tend to be missing, increasing the likelihood of a compensatory stress response – predisposing a person to hypersensitivity to conditions which increase stress.

Again, it goes back to the beginning. What were the causes of one’s initial condition? What underlying factors caused one to have unexpected (though really expected if the underlying conditions were considered) effects of treatment? In medicine, this is the same as asking what is the pathophysiology of one’s illness. Only when the complete or as complete a list of the pathophysiologist of one’s illness is determined can a smooth treatment be obtained. Usually there is more than one pathophysiology when mental function is involved (e.g. fatigue, panic attacks, insomnia, impaired concentration, etc. etc.). Sometimes we can’t initially determine all of the underlying problems. Then the treatment becomes incomplete. Hopefully we keep trying.

@Figuring 2928 wrote:

I’m also taking DHEA and pregnenolone. They seem to help my mood some but have not done much for my major issues.

I am not a doctor.

Do you happen to have pregnenolone and progesterone tested?
Post results.
If they are low, this may help you.

Describe what kind pregnenolone are you taking?

In my case, the only pregnenolone that made to the blood stream so when I tested I could see the difference, is:

Sublingual Pregnenolone from source Naturals, comes in small pills I find it hard to use.

Pregnenolone that actually works for me (and number of people that I have a contact with), is over the counter:

Nutricology Pregnenolone Micronized Lipid Matrix, 150mg (scored)

They also make 100mg and 50 mg
but I think that 150mg tabs are very convenient.

You may want to try this pregnenolone, (75-300)mg/day taken at wakeup time.

It actually works.
You should stop day before supplementation with
HC(cortisol)
DHEA
progesterone
florinef(aldosterone)

if you are taking thyroid hormones, you may want to stop them two days earlier or reduce by 1/2 (just to play safe).
Expect increased conversion T4—>T3 (within an hour) and reduction in RT3 slowly.

If it makes a difference, you may want to vary dose until you figure one that suits you best. (75-300)mg/day always taken at wakeup time.

When you reach stopping point, may want to test pregnenolone and progesterone.

Making further adjustments, aim at about top levels of pregnenolone and progesterone.
If you need, use over the counter Progesta-Care from Life-Flo, to tweak progesterone.

When you reach plateau, consider this testing (must be at Quest Diagnostics):

1

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CAH Panel 6B (Comprehensive Screen) (10299X)
2

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Estradiol [4021X](13- 54 pg/mL)
3

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Estrogens, Fractionated, LC/MS/MS (36742X)*
4

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Testosterone, Free, Bio/Total (LC/MS/MS) Code: 14966X
5

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Dihydrotestosterone*
6

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3a-Androstanediol Glucuronide
7

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Pregnenolone, LC/MS/MS (31493X) 28373P
8

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DHEAs
9

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Aldosterone
10

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7:30AM/12PM/3:30PM—Cortisol, Free and Total
11

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CBG (CortisolBindingGlobulin)
12

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Renin Activity, Plasma
13

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ACTH, Plasma
14

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Comprehensive Metabolic Panel w/EGFR
15

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CBC w/ diff/PLT
16

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T3, Total
17

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T4, Total (Thyroxine)
18

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T3, Free
19

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T4,Free
20

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T3, Reverse
21

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Ultrasensitive TSH
22

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Thyroid Peroxidase and Thyroglobulin Antibodies
23

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Thyroglobulin
24

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Thyroxine-binding globulin
25

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T3 Uptake
26

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SHBG
27

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DHT
28

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Prolactin
29

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IGF-1
30

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IGFBP3
31

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Ferritin
32

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Lipid profile

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#1 is interesting test.

http://www.questdiagnostics.com/hcp/testmenu/jsp/showTestMenu.jsp?fn=10299N.html&labCode=SJC
CAH Panel 6B (Comprehensive Screen) (10299X)
Congenital Adrenal Hyperplasia(CAH)
Test Components
30543X*- 11-Deoxycortisol, LC/MS/MS, Serum
67652P*- 17-Hydroxypregnenolone, LC/MS/MS
17180X*- 17-Hydroxyprogesterone, LC/MS/MS
17182X*- Androstenedione, LC/MS/MS
11281X*- Cortisol, Total, LC/MS/MS
16568P*- Deoxycorticosterone
21964P*- DHEA (Dehydroepiandrosterone), Unconjugated, LC/MS/MS
17183X*- Progesterone, LC/MS/MS
15983X*- Testosterone, Total, LC/MS/MS

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Supplement with Selenium, iodine/iodide.

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