Is it the chicken or the Egg?the-chicken-or-the-egg-1


No, I am not talking about produce or your local farmer’s coop.  I am talking about stress.  More specifically, I am talking about cortisol.


I can still recall my discussion with a colleague recently: the colleague said, “I don’t believe in the words adrenal fatigue”.  I found that odd.  A physician concerning herself over the use of words?  Whether it is adrenal fatigue, adrenal exhaustion, or hypoadrenia, whether one believes in it or not— it exists (kind of like the “earth is flat society”).  As if saying I don’t believe in words, thus that which the words describe does not exist.  As if fibromyalgia didn’t exist until the words fibromyalgia came to be.  This is Illogic at the least and lunacy at its worst.  Sounds more like the word police.  For the purpose of this post, I will refer to adrenal fatigue as hypoadrenia just in case this individual happens to read this post.  I don’t want words to get in the way of this physician learning the truth.



I will have to give this colleague a little bit of credit.  The point that too  many patients  are prescribed cortisol for adrenal fatigue is a problem.  The point that patients are evaluated with only a 1 point cortisol evaluation in the morning or evening is inadequate.  I have seen many clients with hypoadrenia improve with cortisol.  In contrast, I have seen many with hypoadrenia get worse with the same treatment of cortisol.  They both present the same, symptoms of fatigue and low cortisol on testing, yet the same treatment results in profound differences in outcome.


Why and how can this be?


Hormones are complex.


I previously discussed the complexity of hormones.  As I have stated before, it would be simple if men were just Testosterone fueled erections and women were just Estrogen sponges.  This is the way marketing-based medicine presents hormones, but the human physiologic experience is just a little more complex than that.  Thank goodness our physiology doesn’t care to follow the 30 second TV ads and the billboard ads that our short attention, sound bite nation does.  Our physiology could care less what marketing or the word police say.


Cortisol is no different.


Cortisol is the well known stress hormone produced by the adrenal glands.  The adrenal glands produce many important hormones, but cortisol is one of their more important hormones.  The adrenal glands sit on top of the kidneys.  Cortisol is the fight or flight hormone that takes over in chronic stress.  Acute or short-term stress is more driven by the catecholamines—norepinephrine and epinephrineCortisol trumps all other hormones Cortisol is essential for life–in dealing with stress that is.  Without cortisol, proper energy production is impossible, proper weight is impossible, hormone balance is impossible, health and wellness is impossible.





(figure 1)


Cortisol exists in 2 forms.  Cortisol is the active hormone.  This is the hormone that gives us the physiologic effects that we equate with the stress response–increased heart rate, increased blood pressure, on edge….  Its counterpart, cortisone, is the inactive hormone.  This is the common form used in “steroid” injections for pain—hydrocortisone.  The body will fluctuate between the 2 hormones via the enzymes 11-Beta Hydroxysteroid Dehydrogenase (11b-HSD) type I and type II.  This fluctuation is often referenced to as the Cortisol-Cortisone shuttle or shunt (see figure 1 above).  Watch our latest youtube video on the Cortisol-Cortisone shuttle for a more thorough discussion with case studies.   The 11b-HSD type 1 favors cortisol production and type 2 favors cortisone production.  This shunt is a balance of the 2 enzymes, 11beta-HSD type 1 and 11beta-HSD type 2, just as much as it is a balance of the 2 hormones it produces.  The Cortisol-Cortisone shunt is not a scientific term, but rather a descriptive term.  The Cortisol-Cortisone shunt gives insight to the physiologic movement of cortisolHormone balance is a biodynamic process with hormones in constant flux and movement up and down pathways.


Cortisol is converted to the inactive cortisone in the periphery of the body by the 11beta-HSD type 2 enzymeCortisone production occurs predominately in the kidneys, colon, and salivary glands.  This is in contrast to 11beta-HSD type 1 which favors cortisol production and dominates in the liver, adipose tissue (fat), ovaries, testicles, prostate, brain, and muscle.


Just as hormones are not static, the expression of 11b-HSD type 1 and 11b-HSD type 2 are not static.  Get an underlying theme?  The expression and thus the activity of these 2 enzymes can be increased or decreased.  The enzyme 11b-HSD type 1 is increased by the following:


  • Obesity
  • Subcutaneous fat
  • Visceral fat
  • Insulin resistance
  • Type II Diabetes
  • Metabolic Syndrome
  • Weight loss
  • Menopause
  • Testosterone (in men)
  • Cortisol
  • Growth hormone deficiency


In contrast, 11b-HSD type 2 is increased by the following:


  • Glucocorticoids (cortisol)
  • Stress
  • Pregnancy


Even these statements are fluid and not static.  The point is that enzymes and their hormone products are in constant flux and hormones need to be viewed in that context–not in a static context.  The evaluation of the exact relationship and influence of the body with these enzymes is relatively new and the exact relationships is being elucidated by ongoing research.


The balance of these 2 enzymes are one mechanism by which a high stress (elevated cortisol) can be managed.  High cortisol is damaging to the body.  High cortisol is catabolic (break down mode) and very dangerous to the brain.  Elevated cortisol has been shown to shrink the hippocampus (memory) area of the brain.  If you have every met someone with PTSD or PTS, you will know what I am talking about.  The body must protect against this destructive process.  The balance of the 11b-HSD enzymes will shift production away from cortisol to cortisone in an attempt to provide this protection.  The balance of these enzymes and the balance of biochemical movement is just as important as the balance of the individual hormones themselves.


Another insight to the Cortisol-Cortisone shunt is provided through the cortisol and cortisone metabolites.  Herein lies another protection mechanism for the body against high cortisolHormones are not static as marketing-based medicine would like you to believe.  To read more about the profound physiologic effects of metabolites, read my previous post on DHT metabolites (progesterone and estrogen metabolites will follow).  Hormones are converted into other hormones and hormones are also broken down into metabolites for the process of elimination.  However, hormone metabolites have activity, just as the parent hormones themselves do.


The primary cortisone metabolite is Tetrahydracortisone.  In contrast, the primary cortisol metabolite is Tetrahydracortisol.  Tetrahydracortisol exists in 2 forms—the alpha and beta form of Tetrahydracortisol (see figure 2 below).  These 3 metabolites can be collectively measured to assess total cortisol metabolism.  This assessment is very important in the proper assessment of cortisol.  For example, low cortisol found in classic hypoadrenia, can be the cause of the hyper-metabolism of cortisol due to chronic stress.  In this example, low cortisol is not the result of hypoadrenia, but hyper-metabolism.  The body is chewing up and spitting out the cortisol faster than it is produced by the body to protect the body against high stress.  This gives the effective cortisol pattern look of hypoadrenia, but supporting cortisol production would be the absolute wrong approach to treatment.  The appropriate therapy in this example is to slow the hyper-metabolism of cortisol and reduce stress.  Pushing adrenal cortisol



(figure 2)



production or even cortisol therapy would be throwing fuel on the fire.  This is why some with low cortisol benefit from adrenal glandular extract and/or cortisol, whereas others with the same symptoms and test results will not.  The balance of the metabolites and thus the movement of cortisol metabolism in the tissue can be calculated by the formula:


Cortisol metabolites (THF)/Cortisone metabolites (THE)


As the diagram above reveals, the enzymes 5beta-reductase, 5alpha-reductase, and 3alpha-HSD are actively involved in the production of these metabolites.


In summary, a 4 point cortisol test is just the beginning.  Never is a 1 point morning or night-time cortisol of any clinical value.   That is a static look at a fluid situation and an incomplete look at that.  The balance of cortisol to cortisone is fluid and occurs through the balance in activity of the enzymes 11b-HSD type 1 and 11b-HSD type 2.   The environment of the individual, in part, dictates the dominance of 11b-HSD type 1 or 11b-HSD type 2.  The metabolites of cortisol and cortisone provide insight into the functional movement in the Cortisol-Cortisone shunt.   The cortisol and cortisone metabolites can aid in the assessment in total cortisol metabolism i.e. hyper-metabolism versus hypo-metabolism, and the balance of the cortisol and cortisone metabolites can help to determine the metabolic preference of cortisol or cortisone in the tissue.  The balance of the enzymes in the tissue (11b-HSD type 1, 11b-HSD type 2, 5beta-reductase, 5alpha-reductase, and 3beta-HSD) are equally as important as the hormones themselves.  It is the balance of these enzymes which helps to explain the differences in how someone with low cortisol can have significant positive effects with cortisol treatment and another can have profound side effects with the same therapy.  What one sees in hormone levels statically, does not reflect what the body is actually doing physiologically.


One must know the individuals entire hormone physiology prior to therapy.  Otherwise, therapy may just be feeding the fire of hormone imbalance.