• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Dr Mariano, HPA axis dysregulation


iherb 10% discount code OPA989,
australia (brisbane)
This is a copy of a thread from another site where Dr Mariano asnwers a patients question on adrenal fatigue and talks about his general field of practice where he tries to blend psychology, psychiatry, neurology, endocrinology, immunology, metabolism, and nutrition together.

Dear Doctor,

Do you think that people who have hypothyroidism since many year's recover from adrenal fatigue ?

I think it's impossible.

When I begin HC, I feel little better and sometimes when I forget my HC caps for one day I don't feel bad t all. Sometimes, when I wake up the morning I feel OK depiste I forget my HC caps.

At this times, 7 year's on HC, I don't feel well when I wake up. I need to wait 45 mn after my cortisol dose to feel good. I I forget my HC dose I feel bad.

My adrenal fatigue is more severe than before.

What wrong with this treatment, because Jefferies saidthat low dose HC doesn't lower your internal production but help to heal adrenal. I disagree with Dr Wilson about adrenal fatigue.

I known many people like me that don't recover from this " adrenal fatigue", may be it's a real adrenal insufficiency.


iherb 10% discount code OPA989,
australia (brisbane)
The answer to your question is YES.

I use the term "hypothalamic-pituitary-adrenal axis dysregulation" these days instead of the term "adrenal fatigue" to better describe what is occurring.

The bulk of my practice generally involves seeing the most severely ill people with complicated illnesses, under extreme daily and often past traumatizing stress. Living, itself is difficult because many of my patients are either homeless, malnourished, living in poverty, under dangerous circumstances, with lack of family support, suffer abuse, are victims of crime, or have some combination or all of the above. And most if not all of them would die by the time they are between 50-60 years old with the usual psychiatric and physical health interventions. Hypothyroidism and HPA Axis Dysregulation occur in the vast majority of my patients. It is what I deal with day in and day out. Once a person develops a mental illness, I know that it takes multisystem failures to cause it.

The fact that one can even post to this forum means one is not as ill as most of the people I treat.

Once I began practicing a highly integrated form of medicine - combining psychology, psychiatry, neurology, endocrinology, immunology, metabolism, and nutrition - with my patients, I became very happy with the results I see. My patients, in general, have improved better than I could accomplish with conventional treatments. And, yes, I would say, the majority recover from HPA Axis dysregulation, and the others are in a recovering state, where the full pathophysiology is not yet addressed.

Note that HPA Axis Dysregulation is a prerequisite for destabilizing mood. Bipolar disorder, Depression, and anxiety disorders infrequently if not rarely occur without HPA Axis Dysregulation which causes impaired cortisol production.

Treatment with Hydrocortisone alone is a very incomplete treatment of HPA Axis Dysregulation.

When one has HPA Axis Dysregulation, the underlying pathophysiology involves problems with the nervous system, endocrine system, immune system, metabolism and nutrition. It is a systemic problem. It has to be approached systematically at several levels. There are numerous vicious signaling circuits that are started, which makes the condition self-perpetuating.

The nervous system is often shifted to a stressed state - high norepinephrine, low dopamine, low serotonin, low GABA, high histamine, high pro-inflammatory cytokine signaling. Automatic defensive programs are activated in the nervous system, resulting in changes in sleep pattern, loss of energy, loss of motivation, changes in appetite, etc. The shift to a stressed state may be an uncovering of a naturally high stress nervous system or be a compensatory state for problems in the rest of the system. Most doctors don't know how to treat the nervous system because they aren't psychiatrists. One of my observations is that one often cannot optimize endocrine function with bioidentical hormone treatment without also addressing the nervous system when needed with nervous system treatments. One colleague, an internist, has learned to use some psychiatric medications (generally antidepressants, occasionally dopaminergic medications, occasionally sedatives) in addition to hormone and nutritional treatment. She achieves much better results than she would have if she only did hormone replacement and nutritional interventions. I told her she was doing psychiatry. She sends me the patients who need a more intense psychiatric treatment. As a psychiatrist, I have a much larger toolkit than she has.

The endocrine system may be off. Hypothyroidism over the long term forces the nervous system to compensate by shifting to a high stress state. This then forces the HPA Axis to become activated - until interactions with the immune system and the nervous system downregulate adrenal cortex cortisol and other cortex hormone production. The Renin-Angiotensin-Aldosterone system may be excessively active. Changes with aging may result in deficiencies such as hypogonadism, which impair control signaling over stress. Insulin resistance, which occurs immediately with increase norepinephrine signaling, leads to excessive insulin signaling, which depresses testosterone signaling, which leads to an increase in insulin resistance. Insulin resistance impairs nervous system function. It also may lead to, along with hypothyroidism, weight gain. Obesity leads to an increase in Leptin signaling - which is pro-inflammatory, as well as the release of pro-inflammatory cytokines from fat cells.

The immune system, generally, becomes overactivated. There is bidirectional communication between the immune system and nervous system and endocrine system. The increase in pro-inflammatory signaling and norepinephrine from the brain leads to more pro-inflammatory signaling from the immune system. Inflammatory reactions such as due to infection, lead to increased pro-inflammatory signaling. This can trigger more stress signaling, and trigger defensive nervous system programs - similar to instincts, but occurring at the autonomic, unconscious level.

Poor nutrition - which is the bulk of modern diets even those that seem nutritious - impairs metabolic function, which in turn impairs the reception of signals from the immune system, nervous system, and endocrine system. For example, iron deficiency or suboptimization, significantly impairs recovery of the HPA Axis. So long as ferritin levels are low, the adrenal can't function well, no matter what the treatment. Low iron also forces a compensatory shift to a stressed nervous system. Suboptimal nutrition - including the lack of saturated fats and cholesterol in the diet, the lack of complex foods and highly dense nutritious meals - impairs metabolic function. Multiple areas in the world are minerally deficient - leading to minerally deficient vegetables. They look the same but don't have the nutritional value of foods years ago. Fat soluble vitamin deficiencies are very frequent. Vitamin D deficiency is frequent - without Vitamin D, serotonin and dopamine signaling is impaired, insulin resistance worsens, etc. B-vitamin deficiencies prevent thyroid hormone from working.

These are just some of the physical aspects of HPA Axis dysregulation. There are complex interplays between the systems. The psychological and social aspects are another huge area to examine and treat.

When one sees the complex underpinnings of HPA Axis dysregulation - or "adrenal fatigue", then one can see how Hydrocortisone treatment is only one limited aspect of treatment.

These days, in many patients, I often don't even use hydrocortisone for treatment for severely ill patients. If anything, for many people it is too weak a treatment when there are much more pressing issues to address in the system. It can be very important, however, if trauma is present. Hydrocortisone and other glucocorticoids can be very effective in helping the brain avoid focusing on traumatic memories, and instead focus on the task at hand. In treating trauma, it is highly important to enable the person to compartmentalize and seal off traumatic memories in order to focus on the here-and-now. Traumatic memories only serve to overwhelmingly increase stress signaling, which sets up a domino effect on the entire system. Usually, patients with posttraumatic stress disorder have the lowest cortisol levels I see. Generally, when I see a cortisol below 5 (where ideally it should be around 17-20 in conventional units), I suspect posttraumatic stress disorder. PTSD can cause adrenal insufficiency.

Also, given the need to consider replacing also DHEA, Pregnenolone, Progesterone, Testosterone, Estrogen, Aldosterone when one does adrenal functional support treatment with hydrocortisone, one can also see that Hydrocortisone alone often can't be done as monotherapy.

In closing, the whole system has to be considered when assessing "adrenal fatigue" in order to determine as much as possible, the systemic causes and the treatments for those causes. Only until this is done does recovery have a chance to occur.

One of the most important areas to start treatment is nutrition. It has to be optimized as much as one can afford in order to optimize cellular metabolism so hormones and other signals can work in the first place. This is why I recommend high density nutritious traditional diets - such as described in the book, Nourishing Traditions - a good starting point. If one can't change the diet, supplements are needed. Supplements may be needed if the food itself is missing nutrients. If one can optimize nutrition first, it makes the rest of treatment much easier to accomplish.


iherb 10% discount code OPA989,
australia (brisbane)
Originally Posted by Jean
Depiste a good diet I have no optimal Zinc, Iron, copper, vit E gamma (all are low)

I know that my residual fatigue go away when I take ritalin. I AGREE WITH YOU the importance fo the brain function and NERVOUS SYSTEM.

But the problem, after three day at 10 mg/day of ritalin, my brain NA is depleted and I'm worse than before (depress, more tired...)

Ritalin, despite being a relatively mild stimulant, is actually excessive for many people with HPA Axis Dysregulation and suboptimal cortisol signaling.

Increasing Norepinephrine is generally not the best idea for most people with HPA Axis Dysregulation with suboptimal cortisol signaling. The reason is that it worsens this condition. This is why a person only lasts a short time. Brain norepinephrine is not depleted. The rise in norepinephrine from treatment with Ritalin worsens immune system overactivity, leading to worsened HPA Axis Dysregulation.

Unless Cortisol production is at least 12 or more, I generally would avoid a stimulant unless it is a last resort.

If Zinc, Iron, Copper, vitamin E are all low, the diet is NOT good enough.

Meats are a good source of these. I would wonder if animal protein intake isn't high enough.

Note that nutrient dense diets can vary. The traditional Eskimo and Masai diet is essentially totally meat and fat. It is a healthy diet.

If the foods themselves are deficient in nutrients, then supplements have to have to be used.

If the above nutrients are deficient, then the primary problem is a metabolic problem. The cells themselves do not function well. Thus cortisol production is low because the adrenal cortex itself can't make it. Nearly every enzyme involved in cortisol production has iron as part of its structure.