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.
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.
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.
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.
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
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.