Rant: "Normal" cortisol results and cortisol testing.

"Treatment surveillance of chronic glucocorticoid replacement is mainly based on clinical grounds because no objective assessment has proven to be reliable for monitoring replacement quality. ACTH cannot be used as a criterion for glucocorticoid dose adjustment, since in primary adrenal insufficiency it is invariably high before the morning dose and rapidly declines with increasing cortisol concentrations after glucocorticoid ingestion.122,124 Aiming at morning ACTH values continuously within the normal range would, therefore, lead to chronic overreplacement."

 Arlt, W., & Allolio, B. (2003). Adrenal Insufficiency. Lancet, 361, 1888

It is clear in the adrenal insufficiency literature that cortisol ranges are useless for determining a patient's cortisol replacement needs yet uneducated, poorly read doctors continue to ask their patients to submit and pay for cortisol and ACTH testing to determine the patient's replacement needs.  There are no reference ranges for cortisol replacement!  How can any determinations be safely made by your physician if there is no data?

A doctor will ask you to get a morning cortisol test and sometimes ACTH.  Did he tell you how much HC to take?  Did he tell you when to take it?  Does he have literature to determine what the proper numbers should be based on dosage of HC and timing of the dose (the answer to this is NO because it does not exist.  If you have access to this literature and I am wrong, PLEASE post a link in the comments.  I want to be wrong about this.)

The way you feel and your symptoms have to determine cortisol replacement.  Doctors constantly want us to take lower and lower doses of HC but the medical literature says replacement needs to be based on "clinical grounds".  The Arlt and Allolio quote is just one of many reinforcing this position.
A well meaning doctor might ask you to pay for an ACTH serum test to help you determine your cortisol replacement.  He's misinformed.  ACTH is a poor indicator of cortisol replacement and getting this test done can actually harm you if the results are interpreted incorrectly...and they will be interpreted incorrectly.  Your doctor might suggest you start taking less HC or more without taking your "clinical grounds".  Duh!  Are you constantly nauseous, have diarrhea, hypoglycemia and/or low blood pressure but your ACTH draw is low?  Does your doctor want to lower your HC dose based on the ACTH result but not want to pay attention to the fact that 1)  ACTH can't be used to determine HC replacement  2)  it has to be done under specific lab conditions and it probably wasn't  3)  it has to be done first thing in the morning  4) ACTH is pulsitile and fragile so even under the best of circumstances, it can still have an abnormally low result.

Enough about the futility of the meaninglessness of ACTH results.  On to the dangerous misinterpretation of cortisol testing in the undiagnosed.

Doctors will often randomly test cortisol in the undiagnosed yet have NO CLUE as to what the results should be.  They look and see if the lab flags the result as "High" or "Low".  This is one of the most misleading and dangerous things an uneducated doctor can do.  The range is usually 2-20 (give or take, depending upon the lab).  Anything that falls within that range is considered "normal".

Let's look at the "normal" range more closely.

A morning cortisol (8 am) should be somewhere around 20 with the person being asymptomatic for adrenal insufficiency.  An 8 am cortisol of 15 or lower (in someone who is undiagnosed) is a reason to run an ACTH stim test.  Let's just use a little common sense here. A decent morning cortisol should be 16-20ish based on the fact that a cortisol of 15 or lower is grounds to run an ACTH stim test.

A midnight cortisol should be 2-4.

If you have an 8 am cortisol of 12 and a doctor who doesn't know that the cortisol reference range is 2 at midnight and 20 at 8 am.  You're screwed and dismissed as normal despite all of your other symptoms that correspond with adrenal insufficiency.  You are a victim of the "normal" reference range.

Get copies of all of your labs.  Study them.  Learn what they mean.  Search out health forums (mine is free) and get help.  I can provide assistance and guidance if you want to pay for it.  If you suspect you have adrenal insufficiency, you are probably right.  It's hard to convince a physician who only sees "normal" numbers.  All of the numbers need to be taken into account, so do symptoms and past labs.

Rant: Reference ranges can be meaningless (Alternate title: Ma'am your results are normal! You are actually depressed.")

You read that right, reference ranges can be meaningless or even misleading to your healthcare practitioner.  For people with adrenal insufficiency, reference ranges that apply to "normal" populations do not apply to us.  Reference ranges themselves are ridiculously flawed as well.  Applying flawed ranges from the wrong population to people with adrenal insufficiency is a terrible idea for people whose major symptom is fatigue.

On the other hand, I'm not saying to totally and completely disregard reference ranges either.  The numbers you get and where you fall within the reference range, when paired with symptoms and other tests that should be run with one another can be worth their weight in gold.  The numbers can point you in a direction for research that's specific to your condition.

Thyroid as a classic example

• It's suggested that each lab that runs TSH testing establish it's own, standardized ranges due to differences in assay performance.  Often, they don't.  The doctor who interprets your labs does not know whether or not the lab has done this.
• TSH normal lab ranges vary from .5 to about 4.5 yet 80% of the US population has a TSH of around 1.5.  When you're on thyroid replacement, TSH is a useless indicator of replacement status since the thyroid feedback loop is interrupted by thyroid replacement medications.
• TSH is often run on its own.  In populations such as the adrenal insufficient population, TSH can be useless or misleading.  TSH can look "low" as in outside of the lab range.  Usually, low TSH makes it look as if someone is hyperthyroid.  In AI populations, any number of problems can exist.  One of the most misleading, a pituitary or hypothalamic deficiency/autoimmune issue/adenoma which keeps a person from releasing TSH.  TSH stimulates the thyroid to make the bioavailable hormones.  If the thyroid is not getting enough TSH, not enough thyroid hormone will be released by the thyroid and the person will be hypothyroid.  A doctor will only half the picture will lead the patient on an expensive, unnecessary, complicated journey.  Everything could have been figured out quickly by running the pair of numbers that are a good indicator of thyroid status for a person NOT on replacement thyroid hormones:
• TSH
• free T4
• You may ask, "Why free T4? My doctor runs Total T4, isn't that good enough?"  Nope.  Let's talk reference ranges.  Your total T4 can be well within the normal range but the free (bioavailable) portion, the part that controls your metabolism and regulates how you feel, is affected by binding proteins.  When you have adrenal insufficiency, you may be deficient or over replaced on other hormones which affect how much bioavailable thyroid is available to your body.  If you're replacing estrogen, you HAVE to get free T4 tested!  Estrogen changes the binding proteins so that more thyroid is bound to proteins (so your Total T4 looks "normal") but you will be symptomatic for thyroid issues because very, very little is "free" or available to keep your metabolism working.
• The "normal" free T4 range is often .9 to 1.7.  Doctors refuse to acknowledge your symptoms if your frees are within the "normal" range.  Most women with AI feel best at a certain free T4 and men at another (anecdotal evidence).  This is probably because people with AI have a fixed amount of cortisol with which to process thyroid hormone.  Some doctors seem to consider it a crime against humanity for people on thyroid replacement to desire to have a midrange free T4.  I don't understand why.  Why have a reference range if you can't shoot for a sweet spot within it where you're asymptomatic?
• Thyroid has a circadian rhythm, "normal" ranges have been determined for a morning blood draw.  How many times has your doctor shuffled you off to the lab in his office right after your appointment in the afternoon.  Afternoon thyroid blood draws are flawed and the ranges used by the lab are useless.

Thyroid is just one example of the many ways reference ranges can be meaningless.  Labs need to be run the same way every time so you can compare apples to apples.  They need to be paired with other labs to have any meaning what so ever.  Reference ranges have to be evaluated in light of the comorbid conditions of the patient and medications that are being taken by the patient, when they were taken and in what dosage.

Don't despair if you feel awful and your test results are "normal".  Keep collecting your results, keep trying to understand them keep asking for help.  What I've found is that with more comprehension of the tests I've had done to me, the more I understand that "normal" results were completely and totally abnormal.  When I've felt terrible and had "normal" results, I was told I was depressed.  No, I wasn't depressed, I was dying.

Watch for Part 2 of this rant.  "Normal" cortisol results and cortisol testing.

Rant: If your lab test results are not accurate, you're screwed. Take responsibility for yourself.

Sadly, your doctor has no clue about the protocols that need to be followed for drawing the blood tests he orders.  He might know what labs to order but what time of day, fasting vs. non fasting, diet, medications that are okay to take before or not and so on.  He definitely doesn't know what tube needs to be used, if the blood needs to be iced and/or centrifuged.  He should not know those things, they are beyond his scope.

Often, your doctor has no clue which labs to order for adrenal insufficiency.  That is another story entirely and I will probably go into depth about it in a book or upcoming blog post.

The phlebotomists, in my experience, run tests the way they have always done them.  Sometimes, they accurately record whether I was fasting or not.  I am not cutting on phlebotomists.    My guess is that the pay is not fabulous and the clients are not always the most pleasant.  It's always cold, crowded and rushed in the labs.  The working conditions are not ideal.  Add to that, a few of the tests we as Addisonian's require, are uncommon.  The phlebotomist probably assumes that the doctor has given the patient direction about time of day, medications and  fasting.  A phlebotomist is not a babysitter, a doctor is not a babysitter.  You need to be responsible for you.

Being responsible for yourself when it comes to health care or getting blood drawn is not something you should assume others will do for you.  It is something you need to do for you.  The United States was ranked 37th in medical care by the WHO in 2014.  HELLO!  Pay attention to as many aspects of your health care as possible (if you are able).  If you are unable to pay attention to protocols and labs, recruit someone from your circle of friend or family who can or hire me to do it.  Start with providing your doctor with accurate symptom information, next get your tests done as accurately as possible.

Think about this.  If the tests you have done are inaccurate, the interpretation will be inaccurate and your diagnosis or medications that the tests are based on will be inaccurate.  After all of the struggles you have gone through to get a doctor to listen to you and run these tests, do you need inaccurate and expensive as well as potentially useless tests done?    The answer is simple.  The answer is, "No!"  Inaccurate testing can be dangerous or even lethal if medications are administered or adjusted based on inaccurate information!

You do not have to be "bold" or "confrontational" (thank you for thinking I am "bold" in the lab.  Usually, I play the dumb girl who cries and hands a paper to the phlebotomist) to have your tests run as accurately as possible.  You or your advocate will need to know the following information:

• What tests are being run? Get the list from your doctor.
• What is your doctor attempting to accomplish with the information he receives from the tests he is running?  Is it a baseline test?  Being done out of curiosity?  To adjust current medications?
• If you want the BEST interpretation possible from your test results, ask how the results will be interpreted BEFORE the test are run.  For example, what is a normal result for an upright renin draw.  Correct answer, middle to upper third of range with a sodium of 139-141.  See Arlt and Allilo's Adrenal Insufficiency published in the Lancet in 2004.  Page 1889.
• What lab will be running the results?  Call the lab prior to the test to see where they send them or what protocols they follow.

Next:

• Go to the lab's website or use one of these to get a good idea of what protocol will be used.
• Labcorp.com Test Menu
• Quest Diagnostics Test Menu
• Hire Addison's Support Advocacy to do this for you.  Shameless plug.
• Print off each test protocol.
• Read it.
• If something stands out, highlight it.
• Let's take renin for example
• Seriously, look at this one.  It's got a lot of stipulations.  They screw it up and it's going to be WRONG and then your doctor will put you on more or less Florinef than you need to be on.  
• If the renin is not paired with sodium and is done wrong, there's yet another opportunity for misinterpretation of the results by your doctor that could actually kill you.
• If your renin shows up too high, your doctor will put you on too much Florinef causing you to retain too much sodium, have too little potassium and your blood pressure will sky rocket.  Next, you will be put on unnecessary potassium supplements that will sky rocket your potassium and give you an upset stomach.  High potassium can give you a heart attack that kills you.
• If your renin shows up too low, your doctor will cut your florinef.  You will be unable to retain sodium properly, your potassium will sky rocket and you could have a heart attack.  You will be orthostatic (dizzy when you stand up).  You will be fatigued from low sodium.  Low sodium over a long period of time causes osteoporosis.
• Go to the lab the day/morning of the test having fasted if required, be there at the right time (some tests need to be run at certain times of day for proper interpretation-free T4, for example).
• Bring your protocol sheet from the lab's website.
• You can very nicely say that you know X test is somewhat uncommon and you've brought the protocol in case she (the phlebotomist) needs it.
• Observe whether the right tube was used, if the blood was iced or centrifuged.
• Refuse the test if the phlebotomist refuses to use the tube that the lab specifies.  You are a customer and you are paying for it.  

Starting with the right protocol for your blood tests is the starting point for getting the correct diagnosis as well as correct interpretation of results for adjusting medications.

Tests that need special protocols followed to give accurate results:

• ACTH
• Renin
• Sodium
• Ionized Calcium
• free T3 and free T4
• ADH 

You might think that me suggesting asking the lab to follow proper protocol is pushy and not right.  If you think this, you are destined to always feel that there is "nothing wrong" or you "don't deserve to be treated properly".  Stop being a martyr.  Believe that you deserve to feel well and be believed by your doctor.  Your symptoms are real.  If they weren't, you wouldn't humiliate yourself by going to the doctor and sharing your most intimate details of your bodily functions. You deserve good health care.  Go get it!