Hypothalamic Sampling Hormones Requires Blood Flow

Sampling of hormones (including the sex hormones) by the hypothalamus requires consistent blood flow. In the body, blood carries hormones released by endocrine glands and carries them to body parts that need them.

In parasympathetic withdrawal, diagnosis is usually considered adrenal fatigue. The volume of blood shifts from the muscles and brain to the central abdominal compartment. The blood flow to the brain is not stopped when this occurs. The flow is reduced and Poiseuille’s Laws come into play.

The circulatory system provides many examples of Poiseuille’s law in action—with blood flow regulated by changes in vessel size and blood pressure. Blood vessels are not rigid but elastic. Adjustments to blood flow are primarily made by varying the size of the vessels, since the resistance is so sensitive to the radius. This is done by the Abdominal Brain through the release of NeuroEndocrine transmitters, i.e. Serotonin – sero = “blood”, tonin = “pertaining to”.

A 19% decrease in flow is caused by a 5% decrease in radius of the blood vessels. The body may compensate by increasing blood pressure by 19%, but this presents hazards to the heart and any vessel that has weakened walls.

This decrease in radius is surprisingly small for this situation. To restore the blood flow in spite of this buildup would require an increase in the pressure difference of a factor of two, with subsequent strain on the heart.


In severe and/or chronic illness, profound changes occur in the hypothalamic-pituitary-thyroid axis. Ischemia and inflammation disrupt the porous Blood-Brain-Barrier surrounding the hypothalamus. The observed decrease in serum concentration of both hormones and neuroendocrine transmitter (neurotransmitters in the blood) are not compatible with a negative feedback loop.

Ischemia is a restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism (to keep tissue alive, healthy and functioning properly). Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue or organs. It also means local anemia in a given part of a body sometimes resulting from congestion (such as vasoconstriction, red blood cell aggregation due to insulin resistance/diabetes). Ischemia comprises not only insufficiency of oxygen, but also reduced availability of nutrients and inadequate removal of metabolic wastes.

Hepatic Portal Hypertension

Parasympathetic Withdrawal (vasodilation) with blood pooling in the Abdominal Compartment makes the Movement Compartment and Brain/Spinal Cord Ischemic. At the periphery of the ischemic region, the so-called ischemic penumbra, neuronal damage throughout the body develops more slowly because blood flow arising from adjacent vascular territories (collateral flow) keeps blood perfusion above the threshold for immediate cell death. In the ischemic core, the major mechanism of cell death is energy failure caused by Oxygen/Glucose Deprivation (O2/GD). The hypothalamus and midbrain are most vulnerable to ischemia.

Neuron Vulnerability

Neurons in the most vulnerable areas cease to respond or show only faint responses and develop irreversible ischemic or post-ischemic damage. The hypothalamus responds to ischemic insults rigorously without having irreversible ischemic or post-ischemic damage.

The thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.

There is a well recognized but poorly understood caudal-to rostral increase in the brain`s vulnerability to neuronal injury caused by metabolic stress (insulin resistance).

Several brain regions, including the caudate, hippocampus, and hypothalamus, are vulnerable to hypoxic–ischemic brain injury. During O2/GD, hypothalamic neurons gradually depolarized during ischemic exposure. The O2/glucose deprivation (O2/GD) response induces failure of the Na+/K+ pump. The recovery is slow with chronic ischemic penumbrance

Without oxygen and glucose, neurons cannot generate the ATP needed to fuel the ionic pumps that maintain the ionic gradient across the neuronal membrane, mainly the Na+−K+ ATPase.

In the ischemic penumbra, the flow reduction is not sufficient to cause energy failure, and neurons remain viable for a prolonged period of time after the insult, but the neurons are stressed and critically vulnerable to pathogenic events that may tip their fragile metabolic balance. Excessive extracellular accumulation of glutamate is a major factor contributing to production of cytotoxic nitric oxide, free radicals and arachidonic acid metabolites. These events lead to necrosis or programmed cell death depending on the intensity of the insult and the metabolic state of the neurons. Injured and dying cells have a key role in post-ischemic inflammation because they release danger signals that activate the immune system.

Neurons that demonstrate particular vulnerability to ischemic challenges have been termed “selectively vulnerable neurons”. Of the entire forebrain, the neurons of the hippocampus are the most vulnerable.

Summary: Parasympathetic Dominance causes Ischemia to the Hippocampus, Hypothalamus, and Pituitary producing alterations in the HPA, HPT, HPD and HPG axis.

Chronic Inflammation Uncouples the Adrenals

Chronic inflammation causes the Adrenals (HPA axis) to be uncoupled from the Vasomotor Autonomic System (VAS). That’s correct. Despite the fact that the adrenals are disconnected from autonomic control; many Doctors suspect and treat adrenal fatigue in any patient who has low grade or a chronic inflammation. Why? They didn’t look any deeper, questioning why are the adrenals always showing up in their analysis.

They will tell you with inflammation, it is in your best interest to improve your adrenal function to reduce inflammation. They will say the same  with about any other condition. They always recommend doing adrenal support. The Hypothalamic-Pituitary-Adrenal (HPA) axis is a prominent focus of treatment in patients with chronic health conditions. Adrenal Fatigue Syndrome (AFS) is considered the root cause of the problem.

Adrenal / HPA axis Endocrine Pathway: Note the complete absence of any references to Cortisol as an Endocrine Hormone traveling through the blood after release by the adrenals.

This Endocrine hormone dilemma is caused by  the overactive immune response causing chronic inflammatory conditions and low cortisol levels  occurring relative to the level of inflammation the individual is experiencing.

Adrenal Hormones Pass Through Blood – Brain -Barrier

Adrenal hormones and neuroendocrine transmitters have important influences upon the hypothalamus, and to do so they must pass through the blood–brain barrier. The hypothalamus is bounded in part by specialized brain regions that lack an effective blood–brain barrier; the capillaries at these sites has perforations to allow free passage of hormones and even large proteins and other molecules. At these sites, the hypothalamus samples the hormone composition of the blood. Some of these sites are the sites of neurosecretion, where signals are sent from the nerve cells of the hypothalamus to the posterior pituitary. The hypothalamus secretes substances known as neurohormones that start and stop the secretion of anterior pituitary hormones.

The neurons are in intimate contact with both blood and Cerebrospinal Fluid (CSF). These structures are densely vascularized, and contain receptive neurons that control hormones, regulation of fluid and electrolyte balance.

Read More - Hypothalamic Sampling Hormones Requires Blood Flow



Cortisol is a steroid hormone released into the blood stream by the adrenal glands. The adrenal glands sit on top of your kidneys. Cortisol does not get released into nerves or travel through the nerves. Inflammation damages and disturbs blood flow through out the body and the delivery of Endocrine hormones.

The  HPA axis is an adaptive response for “short-lived” inflammatory responses leading to breakdown of energy stores and energy utilization by activated immune and other cells. This becomes a disease causing factor, if it continues too long, that can drive systemic chronic inflammatory diseases such as the hypothyroid or chronic fatigue syndrome symptoms.

Which Hormone Chart is Accurate?
Technically, Both are correct. The lower is more complete. The upper chart is missing most of the hormones. Are those missing hormones important for your health? Are the missing hormones, contributing to your health condition. You may never know, unless you find a Doctor like Dr. Peterson that uses complete hormone tests.


The response of the hypothalamic-pituitary-adrenal (HPA) axis to chronic inflammation is: 1) low serum levels of cortisol; 2) ambiguous lab results with respect to levels of adrenocorticotropic hormone (ACTH) and cortisol; 3) Uncoupling of HPA axis and Vasomotor Autonomic System (VAS); 4) Symptoms ranging from no symptoms to severe cases of hypoandrogenism (low DHEA which is converting into pro-inflammatory Etiocholanolone), fatigue, and/or mineralocorticoid excess; 5) altered circadian rhythm causing morning symptoms. Low cortisol is associated with problems going to sleep and waking up. Low levels of cortisol in relation to Vasomotor neurotransmitters may be proinflammatory because cooperative anti-inflammatory coupling of the two endogenous response axes is missing.

Chronic inflammation and Adrenal Fatigue are quite closely associated: inflammation contributes to and triggers common, but very subtle, symptoms of Adrenal Fatigue such as brain fog, gastric bloating, pain of unknown origin, depression, anxiety, and reactive hypoglycemia. The real truth is that stress and Adrenal Fatigue is not a mysterious entity at all that always seems to be present.

Adrenal Fatigue consists of many nonspecific but debilitating symptoms. The onset of this condition is often slow and insidious. Sufferers are told that they are stressed and need to learn to relax more. Yes, we all know that “stress kills” to a large extent. But, the question is how?

Inflammation Uncouples the HPA axis

These difficulties in understanding “Adrenal Fatigue” and the HPA axis is caused by the fact that the Vasomotor Autonomic System (VAS) axis and the Hypothalamic-Pituitary-Adrenal (HPA) axis are “UNCOUPLED”  in patients with inflammatory conditions or Hepatic Portal Hypertension (another overlooked condition) .

Cooperation between the Vasomotor Autonomic System (VAS) and the Adrenals (HPA axis) is important in chronic inflammatory diseases to efficiently down regulate inflammation in the body. Research of classical stress systems, such as the hypothalamus–pituitary–adrenal (HPA) axis and the sympathetic and parasympathetic nervous systems (SNS and PNS), is disappointing as findings are often contradicting each other, and counterintuitive, as for example, the finding of low HPA axis activity in chronically stressed and traumatized individuals. This is the basis for the meme of “Adrenal Fatigue”.

If you have chronic inflammation; the chances of Adrenal Supplements working is not good.

DHEA is converting into pro-inflammatory Etiocholanolone

Adrenal testing is popular with many Doctors. Low DHEA is often reported in the results. Complete hormone testing is rarely if ever done. When Complete Hormone testing are used. It become apparent that the low DHEA is due to its conversion into the inflammatory hormone Etiocholanolone. The hot flashes women experience may be due to Etiocholanolone surges. It is NOT a DHEA deficiency.

The reason your DHEA is low is because DHEA is converting into Pro-Inflammatory Etiocholanolone

Etiocholanolone is produced from androstenedione. It causes fever, short term hot flashes, immune stimulation and increased white blood cells. Excessive DHEA supplementation may be the cause of high etiocholanolone levels.

The Vasomotor Autonomic System (VAS) axis and the hypothalamic-pituitary-adrenal (HPA) axis are stimulated in parallel in response to stress factors under healthy conditions. This physiological synergism of the axes stimulated by the hormone Etiocholanolone aims at optimizing immune responses. With inflammatory diseases, one would expect that TNF or IL-6 (TH17) stimulates the hypothalamus, which activates the Vasomotor Autonomic System (VAS) axis and the hypothalamic-pituitary-adrenal (HPA) axis in a parallel fashion.

If lab test report shows DHEA, androstenedione and testosterone levels are low with signs and symptoms of bacterial overgrowth, high pro-inflammatory cytokines IL-1, IL-6 levels, etiocholanolone may be causing symptoms of inflammation, fever, leukocytosis, increased serum C-reactive protein, low iron (hypoferremia), increased IL-1 lymphocyte activation and increased white blood cell activity.

In some cases Etiocholanolone has been known to decrease cortisol in short bursts because it has a higher affinity for the parts of the adrenals (Zona Glomerulosa & Zona Reticularis) which effect mineralocorticoids, salt and water content of your blood, and Androgens (testosterone).

Increased etiocholanolone causes a rapid fall in serum iron and a rise in serum ferritin. This would be diagnosed as an iron deficiency. Read More… Anemia of Chronic Inflammation

Hydrocortisone Treatment

A critical confounder of “Adrenal Fatigue” and the HPA axis is the influence of previous glucocorticoid therapy (Hydrocortisone), which has long-lasting, but often ignored, depressive effects on the HPA axis. Hydrocortisone drugs decrease adrenal function, increase kidneys excretion of androgens (testosterone, DHEA) and increased binding of androgens to globulin making them inactive.

If you have previously used Hydrocortisone creams or Cortisone injections; the chances of Adrenal Supplements working is not good.

Uncoupling May Persist Even After Improvement

An uncoupling of the Vasomotor Autonomic System (VAS) and the HPA axis may persist even following clinically significant improvement. Suboptimal HAVS regulation of the HPA axis in patients, with chronic health conditions remains particularly prominent during periods of stress-induced activation of the two systems.

Uncoupling of these two axes is linked to prior corticosteroid therapy. Uncoupling is enhanced in prednisolone treated patients because prednisolone stimulates the SNS and inhibits the HPA axis even in healthy subjects.

How Should Doctors Treat Adrenal Fatigue?

How Should Doctors Treat Adrenal Fatigue?

If you want to change the fruits, you will first have to change the roots. If you want to change the visible, you must first change the invisible. – T. Harv Eker

It’s frustrating to have persistent symptoms your doctor can’t readily explain. Adrenal fatigue is a term applied to a collection of nonspecific symptoms, such as body aches, fatigue, and nervousness, sleep disturbances and digestive problems. The term often shows up in popular health books and on alternative medicine websites, but it isn’t an accepted medical diagnosis unless it is diagnosed as Addison’s disease.

Proponents of adrenal fatigue seldom recognize adrenal dysfunction is always secondary to other physiological mechanisms 

What are the adrenals? Think of them as the caring grandma. She will not sit down when the family is together until everyone is seated at the table and all are served. But before she sits down, she has to clear the dishes, make coffee and serve dessert. Then she has to wash the dishes, clean the kitchen and make snacks. She’s fatigued because she is always trying to take care of everybody. She is an enabler to a dysfunctional family. Do you think she would be so fatigued if family members would stop bickering long enough to pitch in and help?

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This is not a case where the Alternative medicine community knows something the Medical community does not. While it is true the Medical community does not recognize adrenal fatigue. The Functional Medical community has followed the adrenal fatigue paradigm. This off recognizes other factors are involved because neurotransmitters are tested at the same time as the adrenals. As a result of this, those with ‘failing adrenals’ on the never-ending adrenal program respond to the neurotransmitter support.

Adrenal testing is the “Low-Hanging Fruit” of the Alternative medicine community. 

Adrenal testing is the “Low-Hanging Fruit” of the Alternative medicine community. Adrenal tests do not require a lot of effort and will almost always show adrenal fatigue, like testing the air pressure in a flat tire.

The adrenal glands, located on top of the kidneys, produce a number of hormones and neurotransmitters, including cortisol, noradrenalin, adrenaline – the three main stimulatory neurotransmitters, dopamine – a neurotransmitter and stress hormone precursor, DHEA, aldosterone, estrogen, and testosterone in addition to the little know – eticholanolone – the inflammation hormone. Dopamine, norepinephrine and epinephrine are classified as Catecholamines, which are tyrosine-based stress neurotransmitters produced by the adrenal glands during times of psychological stress or low blood sugar levels’.

Melatonin will not work for interrupted sleep for those with low cortisol levels. Low cortisol levels will allow a person to go to sleep and wake up later during the night. Melatonin suppresses cortisol levels and makes adrenal hormone receptor sites more sensitive. Melatonin would work best for those who simply cannot go to sleep.

Cortisol is a corticosteroid hormone produced in the adrenal cortex (part of the adrenal gland). It is commonly known as the primary ‘stress hormone’. It is involved in the response to anxiety and stress, controlled by the Corticotrophin-releasing hormone produced in the pituitary. Elevated cortisol levels tend to increase blood pressure and blood sugar, and reduce the immune responses/capability. Compared with the neurotransmitter adrenaline, it is very slow acting, in neurological terms. Adrenaline can be released in a small fraction of a second, whereas cortisol requires a whole second to be secreted. Cortisol tends to be more implicated in the long term fight or flight response that afflicts those with long term stress, e.g. autoimmune conditions. Of course, overproduction of cortisol through extended periods of stress will result in adrenal burnout and the eventual underproduction of cortisol and other adrenal hormones.

There are many other factors contributing to the stressing of the adrenals glands and impaired neurotransmitter production in general, such as impaired Dopamine/GABA and Serotonin pathways and energy production, excessive Glutamate and Aspartate intake (results in excitotoxicity and disrupts brain chemistry), excessive free radicals, psychological and physical stress, high carbohydrate diet (especially sugar), nutritional deficiencies, inadequate digestive and amino acid conversion processes, prolonged periods of hunger between meals (3 large, square meals a day approach), recreational/legal drug use (caffeine, alcohol, certain anti-depressants, marijuana, speed, meth, cocaine etc.), and birth control pills etc.

For example, it is very difficult to improve adrenal function if a person is anemic. They will not be able to deliver oxygen to mitochondria for ATP energy production and will be dependent upon glycolosis for energy production. Glycolosis is inefficient and places great demands upon the blood sugar/adrenal stabilizing system. The symptoms of any of the thirteen types of anemia are identical to those of adrenal fatigue.

The use of simplified protocols and models to support adrenal disorders are self-limiting. Adrenal dysfunction is always secondary to other physiological mechanisms that need to be identified. The following physiological mechanisms are the root causes preventing the adrenals rehabilitation:

  • Anemia
  • Dysglycemia
  • Low cholesterol
  • Infection
  • Increased intestinal permeability
  • Surgical menopause
  • Dehydration
  • Inflammation
  • Immune Dysregulation
  • Excess Pro-inflammatory cytokines
  • Deficient Inhibitory neurotransmitters
  • Depression medication
  • Emotional stress
  • Autoimmune
  • Heavy metal due to DMT1 upregulation from inflammation/immune dysregulation
  • Environmental antigen burden

– Case Studies & Principles, page 90-91, D. Kharrazian, Author of Why Do I Have Thyroid Symptoms? When My Lab Tests Are Normal.

Are the adrenals involved? Absolutely, but the best way to support them is by correcting the physiological mechanisms causing them to fatigue. The major factor behind adrenal fatigue is usually a Neuro-Endo-Immune system imbalance.

The Neuro-Endo-Immune (NEI) Supersystem incorporates three vital disciplines: Neurology, Endocrinology, and Immunology. Evaluation of the NEI Supersystem – through the measurement of neurotransmitters, hormones, and cytokines – nervous, endocrine, and immune function, are represented respectively. Assessment of these essential biochemical mediators provides important insight into the root causes contributing to adrenal fatigue. The Neuroscience NeuroEndocrine Comprehensive should be utilized to simultaneously measure adrenal hormones, cortisol, DHEA, neurotransmitters and hormones. The NeuroEndocrine Comprehensive profile includes additional neurotransmitter metabolites, DOPAC and 5-HIAA, to assist in assessing serotonin and dopamine activity. It also includes the addition of the amino acid taurine, which is useful in confirming the extent of the stress response.

One way to develop a plan to correct adrenal fatigue is to measure neurotransmitter precursors using the Metametrix Triad Profile. The TRIAD Profile targets each persons specific needs by integrating three powerful profiles – Organix, Amino Acids, and Allergix IgG Food Antibodies – into a single innovative test offering customized intervention options.

The interrelationship of the biochemical processes between the adrenals, different neurotransmitters and hormones involve extremely complex systems of the body: endocrine system, exocrine system, hormonal regulation, immune system, neurological system and brain chemistry. It is extremely complex and finely balanced. Too much or too little of any system can be very detrimental to the body.

Neurotransmitter and hormones must be evaluated. Patients with similar symptoms can have remarkably different metabolic and nutritional needs. Patients with comparable laboratory results often exhibit widely divergent symptoms.  Adrenal fatigue can be measured and corrected by specific testing.

Are you interested in having your adrenals checked? I invite you to call today to set up your adrenal test.

Concerned about your Gastrointestinal Immune Health or Autoimmune Disease? 

Concerned about your Health?

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