Cortisol Deficiency  (a.k.a. hypocortisolism, adrenal fatigue, adrenal insufficiency)

I had decided not to give patients labels and drugs, but only to prescribe natural hormones and nutrients, I thought it would be
easy work--just replacing sex hormones that to correct age-related losses. From Dr. Rouzier's course I had learned about
diagnosing hypothyroidism according to symptoms and relatively low FT4 and FT3 levels, and optimizing T3 levels/effects with
natural desiccated thyroid (NDT).  I helped many people so much that they referred their suffering friends and relatives to me.
They had fatigue, brain fog, depression, anxiety, headaches, etc. and had gotten little help from the drugs prescribed by
physicians. They were mostly women. I tried to help with ovarian hormone replacement when needed, and with NDT. Many of
responded very well to NDT. Some, however, had no improvement at all. Some actually felt much worse, sometimes even after
just one dose. Some immediately better on NDT, but later felt worse. Some of them also felt worse when I tried to correct their
estradiol or DHEA deficiencies. NDT and other hormones worsened their underlying, long-standing symptoms. I understood that
these negative reactions to physiological doses/levels of natural hormones were not “side effects”. They indicated that there was
some other endocrine or metabolic disorder/deficiency that was being strongly affected by potent T4/T3 therapy, usually for the
worse. The cause was not hard to find.
All physicians are taught that thyroid replacement can worsen adrenal
insufficiency; but they think that adrenal insufficiency is extremely rare
—confined to persons with obvious disease or
damage affecting their adrenal glands (Addison’s Disease) or their hypothalamic-pituitary system. They think that adrenal
insufficiency is always severe, even life-threatening. They cannot imagine that any apparently healthy patient in their office could
have adrenal insufficiency. “Adrenal insufficiency” is actually another archaic medical term; what these patients were suffering
from was cortisol deficiency; better named "hypocortisolism". Hypocortisolism is unmasked when a person is given thyroid
hormone because greater thyroid levels/effects increase both the metabolism of cortisol and the need for cortisol, thereby
worsening the relative cortisol deficiency. With time I realized that T3 and cortisol have very powerful and complex interactions--
they both counteract and enable each other's levels and effects. Oral T3 stimulates cortisol secretion, explaining why some
persons felt better immediately with starting NDT.
Hypocortisolism is the explanation for most anomalous responses to
T4 or T4/T3 therapy.

In researching the various schools of BHRT, I had learned about “adrenal fatigue” and saliva cortisol testing through
compounding pharmacies and saliva testing companies. I began to check saliva cortisol levels in these patients.
Saliva testing
has been proven to be the best way to assess a person’s free cortisol levels throughout the day and night.
I found
that most of these patients had low-in range or low cortisol levels. As I became aware of the many manifestations of
hypocortisolism, I began to see it in more patients, again mostly women. They usually had relatively DHEAS levels on testing too,
but a few had unusually high DHEAS levels. Their symptoms were typical of hypocortisolism and had no other apparent cause.
Their history often provided clues. Their symptoms worsened under stress. They felt much better on cortisol-like (glucocorticoid)
drugs like prednisone or Medrol®. They often had a history of negative reactions to thyroid, DHEA, or estradiol, because these
hormones counteract cortisol’s levels/effects. They often had inflammatory diseases/disorders. They had allergies and/or many
food and environmental sensitivies. When hypocortisolism was the best explanation for their history, symptoms, and lab resutls, I
offered them a trial of cortisol (hydrocortisone) supplementation in physiological doses to see if it would help. The effects were
often dramatic, more so than with any other hormone. Many began to feel more normal after just one dose. Over a few days their
aches and muscle stiffness disappeared. They could think more clearly. They felt energetic for the first time in years, sometimes
decades. Their nausea disappeared and their allergies improved. Their inflammation subsided. Their headaches disappeared.
They felt less anxious. They slept better. Their digestion improved.
By the simplest clinical logic, such dramatic
improvements with physiological doses of cortisol proved that they had been suffering from hypocortisolism.
They
had an endocrine disorder that  currently cannot be diagnosed by conventional endocrine practices.

With time, I began to view almost all otherwise-unexplained fatigue, achiness, cognitive dysfunction and
depression are due to cortisol and/or thyroid deficiencies-- until proven otherwise.
Through my experience and
research I realized that a relative hypocortisolism is common in women—it is an aspect of the female reproductive endocrine
system. This fact is the sufficient explanation for women’s much higher incidences of chronic fatigue, fibromyalgia, career burn-
out, depression, anxiety, allergies, and autoimmune diseases. Since estradiol also counteracts cortisol, hypocortisolism plays a
role in many feminine disorders: premenstrual syndrome, premenstrual dysphoric disorder, endometriosis, hyperemesis
gravidarum and post-partum depression. Indeed many studies have demonstrated a hypoactive hypothalamic-pituitary-adrenal
system in persons with these problems. I gradually came to realize that many of the symptoms and syndromes for which medicine
has no explanation are actually due, in full or in part, to hypocortisolism. This is why glucocorticoid drugs are so helpful for so
many medical diseases, disorders and symptoms. Unable to diagnose the cortisol deficiency, physicians prescribe steroids or  
drugs that stimulate the HPA-axis and increase cortisol levels: SSRI antidepressants (Prozac, Paxil, Lexapro, etc.) and
amphetamines. Many drugs of abuse raise cortisol levels: marijuana, cocaine, ecstasy, nicotine, and even caffeine.

Hypocortisolism plays a large role in many of the medical and psychiatric disorders that afflict people; disorders for
which there is no explanation. These patients all get descriptive diagnoses and drugs.  

Cortisol is, in fact, the foundation of the entire endocrine system. It is essential for our adaptation to the demands
of life, and yet all other major hormones counteract it.
If a person does not have sufficient cortisol effect, they simple
cannot feel of function well. Their quality of life is low. They often cannot replace other hormones that they need--they feel worse
with taking other hormones. Cortisol is our primary stress-response hormone. It is known to help maintain blood sugar levels and
to moderate the immune system and its reactions. However it has many other functions that we do not understand.
Hypocoritisolism causes myriad symptoms: fatigue, aches and pains, brain fog, allergies, frequent infections, low blood pressure,
low stress tolerance, anxiety, irritability, hypoglycemia, frequent nausea, PMS/PMDD, autoimmune diseases, excessive sweating,
teeth grinding, restless legs, hot flashes and insomnia. Sufferers often say that they feel like they always have the flu--and it just
gets worse or better at times. Indeed, cortisol secretion is much more variable than any other hormone. It is affected by many
influences--psychological, physical, life-style, drugs, etc. Stress usually brings on a worsening of the symptoms. Hypocortisolism
promotes hypoglycemia which causes irritability, confusion, headaches, hot flashes, sweating, palpitations, insomnia and panic
attacks. Hypocortisolism varies from mild to severe. Many women suffer from a mild hypocortisolism that does not require cortisol
supplementation. They can feel better with simple lifestyle interventions that reduce cortisol demand or increase cortisol
production. To reduce demand they must eliminate all unnecessary stress--they must learn to say "No". They should maintain a
regular schedule and always get a good night's sleep. They must eliminate all sources of inflammation including foods to which
they are allergic (gluten, dairy, soy, eggs, etc.), environmental allergens, and any infections (teeth, H. Pylori, intestinal dysbiosis,
sinuses, etc.). (The best physicians to help identify and eliminate causes of inflammation are those trained in
Functional
Medicine.) Patients can increase their own cortisol production with vigorous daily exercise, especially in the morning.
Hypocortisolism is the reason why many persons must exercise vigorously every day in order to feel and function
well.
If they do not exercise they suffer from hypocortisol symptoms.  

The conventional approach to the diagnosis of adrenal insufficiency is extremely insensitive. Physicians believe, in
essence, that if a person can make a normal level of cortisol under any circumstances, then they do not have any serious
disease of the HP system or adrenal glands and therefore no degree of hypocortisolism. The usual screening test that doctors
do is an AM serum cortisol level. This is insensitive for a number of reasons. It's reported with a reference range of 5 to
20mcg/dL, yet studies find that a result under 14mcg/dL in a symptomatic persons, is highly suggestive of hypocortisolism. In
addition, one's cortisol level is raised after driving to a lab and anticipating a needle stick. This issues is appreciated by some
endocrinologists, so they perform an ACTH stimulation test. They believe a normal results rules out hypocortisolism. It does not,
as many studies have demonstrated. It only proves that the adrenal glands can make normal amounts of cortisol under maximal
stimulation. he best test of free cortisol levels in the blood throughout the day is a diurnal salivary cortisol profile. Most doctors
do not do saliva cortisol testing, and if they do the results are reported with lower limits of "undetectable", obviously incompatible
with health. So as it is, physicians have no way of seeing the low free cortisol levels in their patients. Based on
research done
by ZRT Laboratories, published studies, and my own experience, I have created these ranges for LabCorp/Quest LC/MS saliva
cortisol tests:

Morning:  0.3 - 0.60  mcg/dL    (30 mins after awakening)     Labcorp range   
0.025 - 0.60
Noon:      0.1 - 0.20  mcg/dL    (right before lunch)                Labcorp range   
<0.01 - 0.33
Evening:  0.05 - 0.13  mcg/dL   (right before dinner)             Labcorp range   
<0.01 - 0.20
Night:      0.02 - 0.07  mcg/dL   (right before bedtime)           Labcorp range   
<0.01 - 0.09

ZRT's own ranges, and those of other labs that use immunoassays are about 50% higher. See
Testing for more information.
Notice that LabCorp's lower limit for the AM saliva cortisol is almost zero, far below the level of 1.8 or 2.0 mcg/dL that defined
adrenal insufficiency in some studies. This is due to applying the usual statistical methods to a symptom-unscreened population
whose levels are skewed towards lower values. However, even saliva cortisol levels cannot tell the whole strogy. More than with
any other hormone, serum cortisol levels do not accurately reflect its effects in the various tissues of the body. Cortisol secretion
is highly variable and cortisol is activated and deactivated within cells by certain enzymes.
So, as with the thyroidal system,
the only reliable guide to a person's cortisol status is his/her symptoms.
Sometimes persons with marked hypocortisol
symptoms have normal-appearing cortisol and DHEAS levels, and yet respond very well to cortisol supplementation. Much of the
hypocortisolism in the population is due to relative cortisol resistance. There are many known mutations of the glucocorticoid and
mineralocorticoid receptors. People can test themselves for these by ordering genetic testing through 23andMe or Ancestry.com
and uploading the results to Nutrachacker.com for their complete mutations profile.However, the mutations we know about are
just the tip of an iceberg of biologic variables that affect cortisol effect in the tissues.


For those who need it, cortisol supplementation improves mood, energy, mental functioning, sleep quality and the
ability to handle physical and emotional stress. It reduces allergies and controls autoimmune diseases.
By definition,
anyone with an active autoimmune disease is suffering from a relative cortisol deficiency. However,
even if physicians
suspect cortisol deficiency, they are afraid to prescribe cortisol (hydrocortisone).
They have no  experience with
cortisol replacement, but have a lot of experience with the damaging effects of
pharmacologic doses of non-natural “steroids”  
(prednisone, Medrol, dexamethasone). They inappropriately generalize this negative experience to cortisol supplementation.
They believe that any dose of cortisol taken long-term will cause the negative effects of Cushing's syndrome. The FDA places
HC in the same drug class as all glucocorticoid drugs and so the FDA-mandated prescriber insert lists all the "side effects" ever
seen with overdosing with any steroid drugs. This DrugThink prevents physicians from understanding cortisol.
The medical
profession simply has not begun to understand cortisol or cortisol replacement.
If a physician prescribes HC or a
glucocorticoid, he suppresses ACTH and therefore endogenous cortisol and DHEA production. DHEAS levels quickly become
low or undetectable.
DHEA is an extremely important prohormone and hormone, yet is completely unknown to
conventional medicine.
There are thousands of studies detailing its contributions to health and the consequences of
deficiency. It is the most abundant steroidal hormone in the human body (20 times more abundant than cortisol, 8000 times more
than estradiol or testosterone!). (See DHEA essay).
DHEA is the body's natural cortisol antagonist and prevents many of
the negative effects of cortisol. The suppression of DHEA by glucocorticoid therapy is the cause of many of its
deleterious effects.
DHEA is anabolic, it maintains bone, skin and blood vessels. For instance, studies show that women on 5
to 10mg of prednisone (like 20 to 40mg of HC) daily will start gaining bone mass when given DHEA. DHEA also improves immune
system function and insulin sensitivity.
Patients who are taking cortisol or any glucocorticoid long-term must replace
DHEA to restore youthful DHEAS levels
: around 200mcg/dL in women, 300mgc/dL in men (daily average). This usually takes
10 to 25mg of sublingual DHEA daily for women, 25 to 50mg for men. If DHEA is swallowed, the dose needs to be 25 to 50%
higher.
In addition, physicians do not understand that glucocorticoid therapy always reduces thyroid levels/effects
to some degree. It reduces TSH secretion and T4-to-T3 conversion in a linear manner, depending on dose. This problem is
invisible to physicians who only check TSH levels. This iatrogenic hypothyroidism also causes many of the deleterious long-term
effects of steroids—including the weight gain. Even physiological cortisol supplementation reduces TSH production and T4-to-T3
conversion to some degree. Therefore any person on cortisol supplementation therapy must be closely observed for
signs/symptoms and relatively low FT4/FT3 levels that would indicate hypothyroidism. If present, hypothyroidism should be
treated with T4/T3 therapy. Any person on cortisol supplementation also requires sufficient sex steroid levels/effects. When
cortisol is properly balanced by sufficient thyroid, DHEA, sex steroid and growth hormone levels/effects, it causes no long-term
health problems whatsoever.

For certain, an excessive HC dose--out-of-balance with other hormones--will cause signs and symptoms of cortisol excess--
similar to Cushing's syndrome. Excessive HC dosing will cause weight gain, facial puffiness, higher blood pressure and increased
blood sugar. Fortunately, as the natural hormone, HC promotes much more fluid retention than the artificial steroids. So over-
dosing is much easier to detect. The doctor and patient simply have to look out for any evidence of over-dosing and reduce the
dose if they appear. What is a good dose? Dr. William Jefferies pioneered the diagnosis and treatment of dysfunctional
hypocortisolism. (See his book:
Safe Uses of Cortisol.) He gave patients 20 to 30mg of HC daily. Conventional endocrinologists
often will give patients only 10 to 20mg/day, regardless of symptoms. These low doses may be sufficient in persons with no
cortisol resistance, who are not rapid metabolizers, and who are deficient in DHEA, sex steroids and FT4/FT3--as are most
endocrinologists' patients. However, when all the cortisol-counteracting hormones are optimized, the HC doses reguired are
higher; typically 30 to 50mg daily. There is no blood test to determine the proper HC dose--it must be based upon symptoms and
signs.
The physician and patient must work together to find the doses and timing of doses that will best reduce or
eliminate all symptoms of hypocortisolism 24hrs/day, without creating any signs or symptoms of cortisol excess.

Usually a person needs to take the largest dose of the day upon awakening, the 1 or 2 additional doses up to the late afternoon
or early evening. Cortisol is naturally low in the evening and overnight so usually need not be taken then. If a person takes their
last dose of HC before 4pm, their endogenous production system will still kick in overnight--a good result if obtainable.

While HC dosing must ultimately be guided by symptoms, seeking the lowest doses that eliminate symptoms,
saliva testing is  
accurate when a person is swallowing HC tablets and can be used to for problem-solving, to determine if there is
obvious over- or underdosing.
(Saliva tests are not accurate if person is taking the HC sublingually or transdermally.) One
can use ZRT's ranges or Dr. Lindner's Labcorp/Quest ranges. Saliva cortisol levels
just prior to the next oral dose should be
low-normal or a bit low for that time of day--since the level was much higher for a couple hours after the previous dose. For
instance, if a saliva cortisol level prior to the noon or dinner doses is high-normal or high for that time of day, then one should try
reducing the previous dose. Conversely, the cortisol dose may be too low if a peak saliva cortisol level at 1 to 2 hrs after a dose
is just "normal"--since it will be much lower at 3 or 4 hrs when the next dose is due. Persons vary tremendously in the HC doses
and timing that they require. In every case the best regimen has to be discovered by trial-and-error.
The goal is always to find
the lowest dose that works
. Cortisol supplementation should only be attempted by physicians who are willing and able to stay
in close contact with patients--especially in the first few weeks of supplementation. Today this task is made much easier by e-
mail. I strongly encourage patients who are starting cortisol to e-mail me within days about their response to taking the hormone.
I ask them to also e-mail me after dose changes. Thus within a couple weeks we can know for certain if cortisol supplementation
is helpful for the patient or not. If not, he/she can quickly taper off the therapy. I prescribe only one-month of HC to start with and
insist upon discussing the therapy in detail at that time in order to determine if therapy should be continued long-term and if the
dose is appropriate for the patient.


Deciding to supplement with cortisol is a serious matter, as cortisol is the body's major stress-response hormone.
A person who requires cortisol supplementation to function and feel well didn't make enough cortisol prior to therapy, and will
make less cortisol in response to stress when they are taking cortisol--due to the variable suppression of their already-weak
ACTH-cortisol production. This suppression is not a sufficient reason to avoid supplementation; the patient has the right to
chose. If patients feel/function much better with cortisol supplementation, they must decide whether the benefits are worth the
suppression of their own production. Of course, to make an informed decision they require accurate information. When taking
cortisol, they must realize that they are taking over control of their body's stress-coping system. They must learn to increase the
dose when they are under more stress, are more physically active, or are ill. They should wear some easily-noticed medical alert
jewelry stating that they have "Adrenal Insufficiency". There are many options today.
See this site for examples. The medical
alert jewelry will prompt medical care providers to look for a medical card, so patients should also carry a medical card containing
the diagnoses, personal identifying information, doctor's names and contact numbers, and medications. One can create a

medical card online.
Patients can obtain an emergency treatment card with specific recommendations for doctors here. One
can also carry a USB drive that contain
s all relevant medical information.
For Health and Quality of Life