Friday, July 10, 2015

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.