Cortisol Related Testing

 

There is a lot of information on the internet about adrenal disorders.   Too little overall cortisol production is classically defined as Addison’s Disease, with the less extreme form currently being called adrenal fatigue.   Too much overall cortisol function is classically defined as Cushing’s Syndrome.   There are many websites, as well as forums, for people with Addison’s, Cushing’s, and adrenal fatigue.    To learn more about these conditions, I recommend doing a search on any of these terms.    Below I present the testing that can be done to try and rule in or out adrenal disorders.    Most of these tests are ones you can do on your own, as I describe in “Testing On Your Own — When the Docs Refuse“.    An endocrinologist, of course, might well want to run additional tests if results indicate.

It seems that it’s hard enough to get thyroid function testing beyond the basic screen for TSH and TT4.   From the stories on the Addison’s forums, it appears even harder to get a physician to take you seriously and test you if you suspect adrenal issues.    As a result, unfortunately, most people with Addison’s aren’t properly diagnosed until they’re within a few hours of death in the ER.    I have several Addisonian friends, and this is how they were all diagnosed, after years and years of a long, slow, miserable decline despite constant complaints to their physicians.   If you truly suspect Addison’s, and you can’t get a physican to test you, and you’re in the US in a state that allows self testing, there’s no reason you can’t run most of these tests on your own.

I also recommend the book “Safe Uses For Cortisol” by William McK Jefferies, M.D., F.A.C.P, 3rd edition.    It’s a hefty read, more geared for clinicians, so be aware of that before you order it.   Lay people with no knowledge of the adrenal or endocrine system would probably have a tough time getting through it.    However, for those able to get through it and understand it, I think it’s well worth the read.   I also think this is something most physicians need to have in their personal library.   Addison’s is considered “the great imitator”, and it should be on the differential list more often than not for many common constellations of symptoms.

 

Cortisol Related Testing:

Cortisol, 24-hr saliva or urine sampling:    Cortisol saliva test kits can be ordered for home use and are probably the easiest way to test cortisol, see here.   I utilized the 6-point tests; multi-point testing gives a better idea of if cortisol is chronically low throughout the 24 hour period.   Saliva sampling for cortisol is well accepted by the research community (ie, many researchers will use these tests for their studies) and by alternative or holistic practitioners as an accurate measure of free cortisol.   For some reason, the traditional medical community has not embraced this, and will use 24 hour urine sampling instead.   Chronically decreased cortisol levels are a marker for partial adrenal insufficiency; a “flat lined curve” indicates overt adrenal failure.  Elevated cortisol may indicate stress.   Severely chronically elevated cortisol is a potential marker for Cushing’s disease.   Testing for endogenous cortisol production shouldn’t be done if a person is on Prednisone, or hasn’t sufficiently weaned off of Prednisone.

White Blood Cells (WBC’s):    This test is usually done with what’s called a Complete Blood Count (CBC).   I can order a CBC in my town for $15.00.   Chronically low WBC’s can be one indication of adrenal insufficiency, and so this should always be considered if repeated blood work reveals low WBC’s.    Another consideration is low or normal WBC’s in the face of overwhelming acute infection, trauma, or stress.   One way to test for this, is to order a CBC when you know you’re sick with a virus (cold or flu); if your WBC’s are still low, that’s something that should be followed up.

Low Blood Glucose or Hypoglycemic Episodes:     Hopefully if this is happening, you’re catching this with your glucose meter.   Otherwise, this is also included in the CMP (Comprehensive Metabolic Panel).   Many things can cause low glucose, and adrenal insufficiency/failure is one of them, so it should be on the list of things to check.

Low Blood Pressure (Hypotension):     You can buy a blood pressure monitor at any drugstore or off of the internet.   Symptoms of low blood pressure can be seen here. Many things can cause hypotension, and adrenal insufficiency/failure is is one of them, so it should be on the list of things to check.

Na/K :    Sodium (Na) and potassium (K) are usually provided with standard CMP (comprehensive metabolic panel) blood work.   Decreased sodium along with increased potassium is a potential marker for adrenal insufficiency.   However, usually by the time this pattern occurs, the person is in overt adrenal failure (Addison’s Disease).   In other words, this is not a sensitive marker for this, and usually only occurs when a person ends up in the ER collapsed in an adrenal crisis with many other obvious symptoms.   However, it’s still an important pattern to look for, in particular, if it’s happening consistently with repeated bloodwork.    In other words, if your sodium and potassium are within the normal ranges, but sodium always runs at the lower end, with potassium at the higher end, and you have symptoms, this is something to keep in mind.

Serum ACTH, cortisol, and CBG (cortisol binding globulin):    CBG is a protein carrier for cortisol.   Measuring this along with cortisol may provide a clue as to whether or not the binding proteins are playing a role in cortisol disorders.   Elevated ACTH in the face of normal or low cortisol is a potential marker for adrenal insufficiency.   Decreased ACTH along with decreased cortisol is a potential marker of pituitary dysfunction as a cause of adrenal failure.

Serum Aldosterone and Rennin:    Aldosterone is a steroid also produced by the adrenal cortex and functions to help keep blood pressure normalized.   Renin is secreted by the kidneys and works in conjunction with aldosterone to keep blood pressure normalized.   Decreased aldosterone with increased renin is a potential marker for adrenal insufficiency.

Adrenocortical autoantibodies:     ACA (adrenal cortex antibodies) and 21-OH (21-hydroxylase antibodies).   Fluoroquinolone Toxicity often seems to mimic autoimmune diseases, therefore it’s important to constantly be on the lookout for potential autoimmune markers.   Positive autoantibodies without corresponding overt adrenal failure may indicate an increased risk of developing this in the future, or highlight a subclinical condition.   Additional adrenal antibody testing and monitoring should be done if these are positive.

ACTH stimulation test:     Note: This test can only be ordered by a physician.   I include it here because traditional physicians and endocrinologists consider this test the “gold standard” to diagnosing adrenal insufficiency.   It will definitively confirm end-stage Addison’s disease, when > 95% of the adrenal cortex is destroyed (usually when you’re in the ER in a full blown Addison’s crisis).   It can be used to help distinguish between adrenal gland failure (low cortisol and aldosterone production) vs. pituitary failure (low ACTH production).    It will not diagnose any stage of “adrenal fatigue” (for example, if something less than 95% of the adrenal cortex is destroyed).   In other words, if 75% of the adrenal cortex is destroyed, and you have a “subclinical” adrenal insufficiency going on, this test most likely won’t pick up on it.     Therefore, alternative practitioners don’t consider this test useful.

 

The adrenal glands produce a number of hormones, with a primary one being cortisol.    Production of cortisol is a very dynamic process, varying from minute to minute in response to stress of any kind, as well as due to diurnal variation.    When stress is high, the adrenals put out higher levels of cortisol to help the body deal with this stress; when stress is low, cortisol production returns to a lower normal level.   Stressors include both physiological stress (such as during illness or trauma) and psychological stress.   It also includes the stress of drinking alcohol, or working out exercising.   This dynamic nature of cortisol production contributes to much debate as to what constitutes appropriate and effective testing and diagnosis of adrenal gland abnormalities.   Complicating matters is that a dosage of natural cortisol that is absolutely necessary for survival at times of increased stress may cause serious side effects if continued after the stress has subsided or if it is given at times when stress is not present.   This leads to question what, if any, correct and effective treatment entails.   As with the thyroid gland, once again the “standards” for testing, diagnosis, and treatment therefore often varies depending on the practitioner seen, leading to much controversy and confusion for patients.

Traditional physicians and endocrinologists.    In general, these practitioners tend to recognize only the extremes of low cortisol (Addison’s disease) and high cortisol (Cushing’s Disease).    Both of these conditions are considered extremely rare in the general population.   FQ toxicity victims have been identified as Addison’s patients both pre and post flox; I’m not sure if Cushing’s patients have been identified.    So the focus here will be on low cortisol issues.

  • Traditionally, patients with Addison’s Disease are typically diagnosed at the end stage of the disease, during a true “adrenal crisis” when over 95% of the adrenal cortex is destroyed or non-functional.   It is only at this stage that the testing is often considered clearly diagnostic, along with the obvious severe clinical signs.
  • Symptoms include a slowly progressive and chronic worsening fatigue, weight loss, low blood pressure episodes with lightheadedness upon standing (orthostatic hypotension), weak and sometimes spasming muscles; nausea, vomiting, or diarrhea, craving salt, personality changes such as irritability, malaise, and depression, and sometimes excessive tanning overall or in spots on the skin.   Another hallmark is chronic infections, both viral and bacterial (often times sinus infections); chronic allergies, asthma, and existing autoimmune conditions are additional clues.   Symptoms can progress over weeks, months, or years.   Antidepressants and antibiotics are typically frequently recommended and prescribed over and over again for this patient population before being properly diagnosed.
  • Unfortunately, these slowly progressive and chronic symptoms over time are often missed or ignored (and treated repeatedly with antidepressants and antibiotics) until a sudden event such as a flu virus, an accident, extreme exercise, or the need for surgery leads to a significant worsening of events and a true life or death medical emergency, called an “Addisonian crisis” occurs.     Presumably, the triggering event could also include fluoroquinolone antibiotics in some patients.
  • Supportive labwork other than cortisol may include chronically low WBC’s (white blood cells); normal or low WBC’s in the face of overwhelming acute infection, trauma, or stress; low blood glucose or hypoglycemic episodes, elevated serum ACTH in the face of normal or low cortisol levels, decreased ACTH along with decreased cortisol levels, low serum aldosterone along with elevated serum renin, low Na (sodium) along with elevated K (potassium), and presence of adrenocortical autoantibodies (ACA and 21-OH).   However, some of the above markers may also not be present until end stage diagnoses.

 

Physicians with an alternative or holistic interest, or naturopaths.    In general, these practitioners tend to recognize not only the extreme of low cortisol in the form of Addison’s disease, but a less extreme, “subclinical” version, commonly labeled “adrenal fatigue”.   The belief here is that adrenal fatigue is often unrecognized and is actually quite common within the general population.

  • With this approach, the belief is the adrenal cortex may only be partially destroyed or nonfunctional, not necessarily 95% of it.   The adrenal cortex may benefit from a permanent low-level adrenal treatment support, or may recover over time with appropriate support if too much damage has not occurred.
  • Symptoms of adrenal fatigue include all the same symptoms as Addison’s.   However, there are a wide number of additional symptoms, many of them less severe versions of the above, such as lack of energy overall, fatigue during certain times of the day, milder depression, mood swings, mental fog, a chronic waxing and waning “under the weather” state, feeling overwhelmed and unable to cope, slow to recover from injury, illness, or exercise, insomnia, etc.
  • Supportive labwork other than cortisol include all the same tests as for Addison’s.   However, many practitioners rely on clinical symptoms and history and a few simple additional tests that may be done on physical exam.

 

FQ toxicity is a traumatically stressful event, both physiologically and psychologically.   Patients with existing undiagnosed clinical or subclinical adrenal issues may progress acutely into Addison’s disease after FQ exposure.   Patients with healthy adrenal status pre-FQ’s may experience elevated cortisol initially due to extreme trauma and stress, and progress to subclinical or adrenal fatigue over time due to continued stress.  Therefore, it’s important to be aware of and recognize the symptoms of adrenal cortex issues, and to monitor over time.

A note about Prednisone and steroids in general:   Cortisol is “nature’s steroid” and is absolutely necessary for life.  Addison’s disease is excellent proof of this, as those with the condition can attest.   Therefore, “steroids” are not “bad” per se; as they are naturally produced by the body in appropriate dosages during both the stressed and unstressed state.   Prednisone and a variety of other steroids, (Dexamethasone, Triamcinolone, etc.) are synthetic steroids, more potent than natural cortisol.   It is quite common for FQ toxicity victims to be offered Prednisone for their symptoms, in particular by rheumatologists, who often see FQ toxicity as an autoimmune or inflammatory condition.    However, because severe FQ toxicity reactions may include severe endocrine disruptions, I recommend that these steroids should not be taken without baseline endocrine testing beforehand.   Additionally, according to informal polls taken of flox victims, 2/3 of them report a severe worsening of symptoms either during or after synthetic steroid treatment, and a number of victims reported that these steroids seem to initiate their severe symptoms weeks to months after cessation of the antibiotic .   Lastly, the drug inserts themselves state that synthetic steroids such as Prednisone are contraindicated with concurrent FQ usage, and patients that have been given both appear to experience more severe reactions in terms of symptoms and duration.   This may be because high levels of steroids actually suppress immune function and adrenal output of natural cortisol, and also mimic a transient Cushing’s Syndrome.    There are accounts of patients improving with steroid treatment; there is a chance these patients were subclinical for adrenal insufficiency prior to FQ exposure, or as a result of it.   For these reasons, I would recommend a comprehensive adrenal workup during the acute stage of FQ toxicity, and as additional symptoms warrant.    Additionally, if Prednisone or other synthetic steroids are to be prescribed or tried, it should be done thoughtfully and judiciously.

 

Table Of Contents