CORTISOL stops inflammation

Cortisol stops inflammation, but causes immune system suppression.
To understand Adrenal fatigue, Chronic Fatigue Syndrome and Myalgic Encephalitis (“CFS/ME”), “burnout”, “long Covid”, Fibromyalgia, “Low T3 syndrome”,Intracellular Hypothyroidism and the tiredness and weakness which accompanies all severe illnesses, one needs to understand and appreciate Cortisol.
To understand Cortisol, one needs to understand the adrenal glands.
Be warned!! – it will be a long journey to understanding.
But there’s no other way, so, let’s begin with the adrenals.

CAVEAT

The major portion of this page is reasonably easy to read and understand.
However the section on “adrenal insufficiency”, an explanation of situations in which the adrenal glands fail to produce enough cortisol, is complicated and rather difficult.
If you don’t have a fairly extensive medical vocabulary, it may be frustrating.

Therefore, while I would encourage you to study this page on cortisol if you can “stomach it”, you may find that all you really need is “the bottom line”.

So here’s the bottom line, in advance

Cortisol stops inflammation, but causes immune system suppression.
Cortisol is an essential part of our metabolism and in an emergency, it is lifesaving.
Synthetic Cortisol, which is much stronger than the natural hormone, is prescribed by doctors to control severe illness and save lives.
However the side effects of long-term treatment with synthetic cortisone can be severe and under some circumstances lethal, because it achieves its effects by shutting down important systems, causing diabetes and loss of maintenance and repair facilities in many organs.

THE ADRENAL GLANDS

Twin influencers, each in its privileged position in the middle of the body.

This pair of tiny (5×3×1 cm, 5 grams), complicated secretory glands sit, one on top each kidney, in front of the 10th-11th rib on either side, safe and protected from trauma.
Each is supplied with blood by three arteries and each excretes its products directly into the big kidney vein, only an inch or two from the vena cava (the biggest vein in the body) and about six inches from the heart.

INTERNAL STRUCTURE of the ADRENALS

Each Adrenal has two layers: an outer, yellow ‘cortex” and an inner, dark red “medulla”.
The CORTEX, only 1 mm thick, has three layers, or “zones” and each zone makes a “Corticoid Hormone”.
The (outer) Zona glomerulosa makes mineralocorticoids, to control Sodium and Potassium in the urine.
The (middle) Zona fasciculata makes Cortisol, the “stress hormone”.
The (inner) Zona reticularis makes DHEA, the raw material for many other hormones.
The MEDULLA makes “Catecholamines”, the “fight or flight”, adrenaline-type hormones epinephrine and norepinephrine, which control heart, skin, muscle, gut and emotional responses to acute emergencies.
Each gland is enclosed in an active capsule, which does its maintenance and repair.
An active capsule is unusual, because every other organ’s capsule does nothing but separate it from the surrounding tissues. (2).

THE HORMONES:

Cortisol (hydrocortisone) is produced by the zona fasciculata.
Cortisol stops inflammation, but it is called a “glucocorticoid”, because it raises the blood sugar.
It does this by triggering conversion of glycogen (our glucose store) into glucose and when necessary, by converting proteins, for example, muscle protein, into glucose, in a process called gluconeogenesis.

THE DIURNAL RHYTHM OF CORTISOL

Cortisol works primarily in the metabolism of fat, protein, and carbohydrates.
It is secreted in diurnal rhythm: a surge of cortisol is released in the morning, with a maximum at 8AM. Then it tapers through the day to an evening minimum.
But the adrenals can produce a surge of cortisol at any time: it is released in response to physical, environmental or emotional stress, so it is called the “STRESS HORMONE”.

All this is good, but Cortisol is, sort of, a “Dr Jekyll and Mr Hyde” hormone.
Its calming, soothing, painkilling, anti-inflammatory effects come at a cost.
Many of its effects are brought about by blocking “cytokines”, which are chemicals that our bodies make to activate our immune system.
The cytokines attract specialised white blood cells to injured or infected areas, to get rid of germs or toxins and repair any damage which has been done.
Some of them, for instance Interleukin 6 (IL-6), are indispensable for healing: without IL-6, the large bowel can’t repair mechanical or infectious damage to the lining mucosa.

So cortisol can be helpful, but prolonged treatment with cortisol can cause trouble.

[1] Cortisol stops inflammation by blocking “inflammatory cytokines” *, but this results in immune system suppression, failure to attract white blood cells to fight infection and slow, inefficient wound healing.
[2] Cortisol supplies emergency Glucose from “Glycogen” stores, but high cortisol leads to muscle wasting, because if there isn’t enough glycogen, it converts muscle protein into amino acids, so that the liver can use them to make glucose.
[3] Cortisol decreases bone formation and healing, and can cause bone loss.
[4] The increased blood glucose that cortisol produces can cause temporary diabetes and diabetes can encourage a mild infection to flare and produce an abscess.
[5] Cortisol slows down all body processes by preventing conversion of Thyroxine (“Thyroid 4”, or “T4”) to “Triiodothyronine” (“Thyroid-3”, or “T3”): this action is intended to save energy, which the body can use for healing; but it slows everything down.
[6] Thus, cortisol even slows production of dehydroepiandrosterone (DHEA).
[7] If cortisol production is high for too long, a dangerous condition called “Intracellular Hypothyroidism” may begin, in which the cells don’t have enough T3 to function.
In intracellular hypothyroidism, the body is liable to “low thyroid symptoms”– viz:
– Low T3 in the cells drops energy consumption and encourages fat formation.
– Low T3 slows the brain down, causing anxiety, confusion, depression and “burnout“.
– Low T3 in the muscles causes weakness, muscle pain, fatigue and constipation.
– Low T3 in the heart causes cardiomyopathy and eventually, heart failure.

* For example, consider what can happen If a diverticulum of the bowel gets infected:
– Interleukin 6 (IL6), a cytokine, is made by the colon to heal the damaged diverticulum.
– But IL-6 in the blood can cause muscle inflammation, eg. Polymyalgia Rheumatica.
– Polymyalgia Rheumatica causes terrific pain.
– Cortisol blocks IL6, so it stops Polymyalgia Rheumatica pain In an hour or two, but the infected diverticulum’s damaged lining can’t heal without IL6.
– Prescribed (synthetic) cortisol also blocks other cytokines that would normally call white blood cells to the infected area to kill germs.
– Keeping germ killing white blood cells away makes the germs happy.
– Cortisol increases the available sugar: this makes the germs even happier.
– The germs multiply in the diverticulum, forming an abscess which can kill the patient.
– In the meantime, cortisol is blocking T3 in the cells and everything in the entire body is slowing down.

NOTES

  • The hypothalamus, pituitary, and Adrenals constitute the “Hypothalamo-Pituitary-Adrenal axis”, (HPA). The HPA controls Cortisol production.
  • Emotional, physiological and physical stress – any kind of stress – causes a release of Corticotrophin-Releasing Hormone (CRH) by the Hypothalamus.
  • CRH travels in the portal passages (tiny tubes carrying hormones from the Hypothalamus) to the anterior Pituitary gland (the “Adenohypophysis”).
    There, CRH stimulates production of ACTH (Adreno-CorticoTrophic Hormone).
  • ACTH travels in the blood to the adrenal cortex, to stimulate production of cortisol.

See the “NEUROSCIENTIFICALLY CHALLENGED” website, at https://www.neuroscientificallychallenged.com/blog/2014/5/31/what-is-the-hpa-axis

The HPA AXIS: the hypothalamus, anterior pituitary gland and the adrenal cortex.
https://www.neuroscientificallychallenged.com/blog/2014/5/31/what-is-the-hpa-axis
From there, Check their UTUBE video, for an explanation of the HPA, at https://youtu.be/QAeBKRaNri0
ADRENAL INSUFFICIENCY (NOT “Adrenal Fatigue”)

Adrenal insufficiency can be divided into primary, secondary and tertiary.

Primary adrenal insufficiency (Addison’s disease), from damage to or dysfunction of the adrenal glands.
Production of all Adrenal hormones falls.
Severe adrenal failure causes Addison’s disease, which can be lethal.

Addison’s disease can be caused by:
Surgical removal of both adrenal glands, or blockage of the arteries by blood clots.
Autoimmune Diseases (when the body’s own immune system attacks itself).
Granulomatous Diseases (e.g. tuberculosis and histoplasmosis infections).
Metastatic cancer, spread from Cancer in another organ, to the adrenal glands.
Pharmacological steroid therapy.
Haemorrhage (bleeding) in the adrenal gland, sometimes from blood thinners.
Septicaemia (infection in the blood) with low blood pressure to the adrenals.
Pneumocystis infection (as a complication of AIDS).
Rare hereditary diseases.
Note that these conditions, except surgery and embolism, develop slowly.

The most common signs and symptoms of Addison’s disease are:
Weakness
Fatigue
Nausea
Abdominal pain
Weight loss
Dehydration
Low blood pressure
Lethargy
Hyperpigmentation (darkening of the skin)

Secondary adrenal insufficiency results from low production of ACTH, by the pituitary gland. If your pituitary doesn’t send ACTH, your adrenal glands don’t make cortisol.
This is much commoner than the primary form.
The clinical features usually have a slow onset with many non-specific symptoms.

Tertiary adrenal insufficiency results from inadequate CRH (Corticotropin Releasing Hormone) being secreted from the Hypothalamus, with resultant decrease in ACTH release from the pituitary.
Causes include brain tumors and strokes, but the usual cause is sudden stoppage of long-term steroid use.

TREATING PRIMARY ADRENAL INSUFFICIENCY
The aim of therapy is to replace the glucocorticoids and in some cases, mineralocorticoids, for as long as necessary.
Synthetic “corticoids” are prescribed, rather than cortisol itself, because they last longer and are easier to control.
Extra glucocorticoid is given for any major stress (e.g. surgery, accident or infection).
The patient can lead a normal, active life, but must avoid infections and must take precautions against emergencies by taking prescriptions faithfully, wearing a medical alert bracelet and staying in contact with support systems.

SECONDARY AND TERTIARY INSUFFICIENCY
These occur with hypothalamic or pituitary damage from trauma, surgery, radiation, infection or tumours, or by suppression of the adrenals with long-term prescription of cortisone. (6)
The clinical features of secondary adrenal insufficiency are similar to those of primary insufficiency, except that hyperpigmentation is not present (because ACTH is not elevated) and dehydration does not occur.
ADRENAL CRISIS

Adrenal Crisis, in which the adrenals are unable to supply sufficient cortisone, is a life-threatening emergency and requires immediate treatment, with intravenous saline to correct low blood pressure and Hydrocortisone to replace cortisol.
In addition corrective treatment is given, for the cause of the Adrenal failure and any other problems.
Adrenal Crisis usually presents as sudden low blood pressure shock in three major groups of patients:
1. Previously undiagnosed patients subjected to major stress,
2. Previously diagnosed patients who fail to increase glucocorticoid replacement during a major illness.
3. Sepsis.

CAVEAT:
The prevalence of Autoimmune adrenalitis is only one in 20,000 persons and the symptoms preceding the crisis (like hyperpigmentation, fatigue, anorexia, orthostasis, nausea, muscle pain, joint pain and salt craving), may be mild.
Although surveillance and “a high index of suspicion” would lead to early diagnosis, these symptoms are often missed, but if the following protocol were applied to all patients presenting with fatigue, adrenal crisis would be truly rare:

EARLY DIAGNOSIS OF ADRENAL INSUFFICIENCY (4)

Anyone presenting with fatigue should have an early morning Cortisol test at 8AM.
If the Cortisol is lower than normal and especially if Sodium is low and Potassium high, an “ACTH stimulation” test can be done, to show if the Adrenals can produce Cortisol.
This test shows whether the Adrenal function is normal or low and differentiates between primary and secondary failure, to allow early diagnosis and proactive, preventative therapy.

THE BOTTOM LINE

Cortisol stops inflammation, but causes immune system suppression.
Cortisol is an essential part of our metabolism and in an emergency, it is lifesaving.
Synthetic Cortisol, which is much stronger than the natural hormone, is prescribed by doctors to control severe illness and save lives.
However the side effects of long-term treatment with synthetic cortisone can be severe, because it achieves its effects by shutting down important systems, causing diabetes and loss of maintenance and repair facilities in many organs.

REFERENCES

(1) THE ENDOCRINE SURGEON, http://www.endocrinesurgeon.co.uk/index.php/adrenals-the-cortex-cortisol

(2) THE ADRENAL CAPSULE IS A SIGNALING CENTER CONTROLLING CELL RENEWAL AND ZONATION THROUGH RSPO3 Genes Dev. 2016 Jun 15; 30(12): 1389–1394. doi: 10.1101/gad.277756.116, PMCID: PMC4926862, PMID: 27313319 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926862/

(3) Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial: Eleanor Gurnell, Penelope Hunt, Suzanne Curran, Catherine Conway, Eleanor Pullenayegum, Felicia Huppert, Juliet Compston, Joseph Herbert, and V. Krishna K. Chatterjee J Clin Endocrinol Metab. 2008 Feb; 93(2): 400–409. Published online 2007 11 13. doi:10.1210/jc.2007-1134PMCID: PMC2729149, PMID: 18000094

(4) ADDISON DISEASE: EARLY DETECTION AND TREATMENT PRINCIPLES: A. MICHELS, MD, N. MICHELS, PhD, Am Fam Phys, 14/4/1 ;89 (7):563-568. see https://www.aafp.org/afp/2014/0401/p563.html and https://familydoctor.org/familydoctor/en/diseases-conditions/addisons-disease.html.

(5) ADRENAL INSUFFICIENCY IN SEPSIS, Djillali Annane  1 , . 2008;14(19):1882-6. doi: 10.2174/138161208784980626. PMID: 18691099 DOI: 10.2174/138161208784980626

(6) GLUCOCORTICOID THERAPY AND ADRENAL SUPPRESSION, Nicolas C Nicolaides, MD, PhD, Aikaterini N Pavlaki, MD, Maria Alexandra Maria Alexandra, MD, PhD, and George P Chrousos, MD, PhD, MACP, MACE, FRCP. Update: October 19, 2018, Bookshelf ID: NBK279156PMID: 25905379 https://www.ncbi.nlm.nih.gov/books/NBK279156/

(7) Burnout and metabolic syndrome among healthcare workers: Is subclinical hypothyroidism a mediator? By Meng‐Ting Tsou 1 , 2 , 3 and Jau‐Yuan Chen
In J Occup Health. 2021 Jan-Dec; 63(1): e12252. Published online 2021 Jul 19. doi: 10.1002/1348-9585.12252
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291686/
ABSTRACT: Evidence suggests that subclinical hypothyroidism (SCH) is associated with burnout and metabolic syndrome (MetS). We examined the relationship between burnout and MetS among healthcare workers (HCWs) and investigated the potential mediation of SCH.




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