THYROID TESTS: PART I

What You Need to Know About Common Thyroid Laboratory Tests

 

By:  Zana Carver, PhD

Updated 3/2/2018

 

Not Seeing the Whole Picture

When my youngest son was awarded a “student of the month” certificate and sticker, I proudly displayed that sticker in the window of my vehicle.  After some time a few of the letters fell off and eventually I’m left proudly displaying the words, “stud    of the month” in my window.  My point in sharing this story is that there are many examples of not having the complete picture.  This is very true in medicine but even more important for understanding thyroid physiology and testing.  It’s not what we know that’s preventing or hindering treatment of thyroid conditions but what we don’t know about the complex interaction of systems and cross-talk between tissues in the body.  For a brief thyroid introduction: https://www.thyroidcode.org/thyroid-introduction-2/

 

Standard Thyroid Lab Tests

  • Thyroid Stimulating Hormone (TSH) test: This is the most commonly used lab test for thyroid dysfunction, and in many cases the only test ordered.  The hypothalamus releases thyrotropin-releasing hormone (TRH) to cause the pituitary to increase production of thyroid stimulating hormone (TSH), sometimes referred to as thyrotropin.  TSH is a pituitary hormone that stimulates the thyroid gland to increase production of thyroid hormones, thyroxine (T4) and triiodothyronine (T3).  A high TSH level may indicate low levels of thyroid hormones (hypothyroidism), and low TSH may indicate high levels of thyroid hormones (hyperthyroidism) (see schematic below).  The normal range for TSH is generally considered to be between 0.3 mU/L and 3.0 mU/L.

    Full thyroid feedback

    Full Thyroid Feedback Cycle

  • Thyroxine (T4) or Free (fT4) test: These tests measure either the total serum levels of T4 that is bound to protein plus free or just the free level of T4 hormone.  Although a total T4 is sufficient for most purposes, whenever there is concern over abnormal protein binding or abnormal protein levels, a free T4 should be measured.  Examples of when a free T4 is more appropriate include, the use of birth control pills or other medications that alter sex hormone binding globulin (SHBG) levels, any liver or kidney disease that can affect blood levels of binding proteins, and when other medications are used that may compete for binding.  The normal range for serum T4 is 5-12 µg/dL, and 0.8-2.0 ng/mL for free T4.
  • Triiodothyronine (T3) or Free (fT3) test: These tests measure the total level of T3 or the free level of T3 in serum similar to T4 tests.  The same conditions for when free T4 levels are more appropriate measures compared to total T4 are also applicable to the use of total T3 or free T3 lab tests.  The normal range for serum T3 is 80-180 ng/dL.  FT3 and reverse T3 will be discussed in greater detail in Part II.
  • Thyroid-Stimulating Immunoglobulin (TSI), Thyroid Peroxidase Antibody (TPO), Thyroglobulin Antibody (TGAb) tests: These tests and other autoimmune thyroid tests help to explain if a person’s immune system is confused and attacking the thyroid gland, receptors, or enzymes associated with it.  This topic will be explained more fully in a separate autoimmune post.
  • Reverse T3 (rT3): This test is useful for detecting altered enzymatic conversion that inactivates T4 rather than converting T4 into functional T3.  It is useful in cases of non-thyroidal illness and some types of thyroid hormone resistance.  Often it’s useful to evaluate T3 and reverse T3 together to get a complete picture of thyroid status.

 

TSH Strengths and Pitfalls

The TSH test is the preferred method for screening patients for thyroid disease because there is an inverse logarithmic relationship between TSH and T4 levels in serum (the liquid portion of blood).  What this means is that for very small changes in T4 levels there is a very large and opposite change in TSH, for example, a 100-fold decrease in TSH for a 2-fold increase in T4 (at least in healthy individuals).  Doctors also prefer this test because TSH levels change slowly (6-8 weeks according to most sources), so they feel confident to use this value as a surrogate for long-term thyroid status.  Lastly, the ultrasensitive 3rd generation TSH tests are incredibly accurate and reproducible even at the extreme high and low ends of the detection range.  This is truly remarkable but just because a test is highly sensitive for detecting the correct level of TSH does NOT mean that there couldn’t be serious misinterpretations of what the TSH levels actually mean.

The TSH test is based on several assumptions including normal communication and response between the hypothalamus, pituitary gland, thyroid gland, and tissues.  Healthy volunteers were used to establish the normal range for TSH, and it is assumed that the hypothalamic-pituitary-thyroid (HPT) axis functions the same in all patients.  This is simply not true and one example would be central hypothyroidism when the pituitary gland is dysfunctional and does not produce enough TSH or does not respond to TRH.  Other examples include thyroid hormone resistance (low thyroid levels in tissue but adequate levels in the blood) and in cases of non-thyroidal illness (previously called euthyroid sick syndrome).  In addition, many medications, chemical exposures, vitamin deficiencies, illnesses, and stress can also affect the HPT pathway and cause erroneous TSH results.  These factors will be discussed fully in Part II of this post.

 

Thyroid Hormone Metabolism

The TSH test assumptions might be true if the pituitary had the same ability to access thyroid hormones and convert T4 into T3 as all other tissues.  This is not the case because some tissues are less permeable and have to rely on transporters to grab on to thyroid hormones and carry them into tissue cells.  T3 is responsible for most of the effects of thyroid hormone and many tissues have to convert T4 into T3 for proper action of this hormone.  So let me give you a greatly simplified overview of this process and explain how the pituitary plays by a different set of rules.

The summarized version of thyroid hormone metabolism involves three classes of deiodinase enzymes that activate thyroxine by converting it to T3 or deactivate it by converting T4 into rT3 (reverse T3).  The enzyme classes that convert T4 into T3 (activation) are type I (DI) and type II (D2) deiodinases.  The enzyme class that converts T4 into rT3 (deactivation) is type III (D3).

Deiodinases and Thyroid Hormone ConversionDeiodinases and Thyroid Hormone Conversion

During illness, the proportion of D3 enzymes in tissues increase, which can cause local deficits in T3 function.  The real issue is that the pituitary has a type of enzyme (D2) with a higher affinity for T4 (more efficient local conversion of T4 into T3) and transporters that are also much better at binding to T4 than transporters or enzymes in other tissues.  This gives the pituitary an artificially higher level of both T4 and T3 than other tissues within the body.

 

TSH Example and Lessons Learned

A great example of the TSH problem was my last visit to the endocrinologist.  My lab results were TSH < 0.015 uIU/mL (0.34-5.60 uIU/mL normal reference range; extremely low/suppressed), free T4 = 1.38 ng/dL (0.60-1.20 ng/dL normal range; just over the normal range), and free T3 = 2.7 pg/mL (2.0-4.4 pg/mL reference range; low normal).  During this visit, I mentioned that I felt much better and that my hypothyroid symptoms of fatigue, coldness, memory and concentration issues and weakness were all much better.  In fact, I reported that all my symptoms were completely gone except for some occasional fatigue.

A very low TSH is considered an indication of hyperthyroidism (high thyroid hormone levels) and those symptoms include nervousness, anxiety, sweating, chest tightness, and heart palpitations.  Even though I had absolutely NO SYMPTOMS of being overmedicated and I felt much better, he decided to lower my dose based solely on his discomfort with my very low TSH.  Did I argue with my endocrinologist, and storm out angry?  No, absolutely not, he could be sued for not following the “standard of care” which uses the TSH normal range to determine the dose of thyroid hormone replacement.  This is part of a much bigger problem that can be dissected further with new posts and new forum discussions.

My slightly elevated T4 and very low TSH may have been related to my taking T4 medication about 30-90 minutes before blood was drawn, having it drawn in the early afternoon, taking ibuprofen the night before, drinking coffee in the morning and afternoon, or eating a large meal before the lab tests were done.  Kent Holtorf, MD stated that 80 % of suppressed TSH levels do not indicate hyperthyroidism, and I believe this is true in my case.  I do not know how often this is true, and doctors are not taught to question the TSH results so what can you do to get lab values that are more representative of your true thyroid status?

 

How to Get More Accurate Thyroid Lab Results

  • Always be consistent with your lab tests, and if you prefer to do it in the morning fasted (I do) then you always need to have morning fasted lab tests. If you prefer to have your blood drawn later in the evening then always do it at exactly the same time.
  • Because of the circadian pattern of TSH release that peaks very late in the evening, I would recommend having your blood drawn either first thing in the morning or as late in the evening as possible to avoid having a falsely suppressed TSH.
  • I recommend fasting before lab tests are done because there are reports of approximately 25 % higher TSH levels during the fasted state. Before my last set of thyroid lab results I didn’t think fasting would matter but now I am a believer.
  • Even though the half-life of T4 medications (levothyroxine and Synthroid are examples) is about 7 days, there will be a falsely elevated T4 level if you take it within 2 hours before your lab draw. Because of this, I would recommend not taking your thyroid medication until after your blood is drawn if you prefer to do your lab tests in the morning and if that is when you normally take your thyroid medication.
  • The half-life of T3 (Cytomel and liothyronine are examples; natural desiccated brands also contain T3) is much shorter, about 1 day. So if you are taking a T3 containing medication I would recommend not taking it until after your blood is drawn.
  • It’s not known how exercise the morning of thyroid labs would affect the results but this is a variable I would like to test for myself and report on in a later post.
  • Do not take any unnecessary medications for several days (preferably weeks) before your lab tests, such as ibuprofen or any type of non-steroidal anti-inflammatory (NSAID) medication. Do not use hydrocortisone cream, a steroid inhaler, or steroid nasal spray before thyroid tests.  If you take daily doses of hydrocortisone or any other corticosteroid, consider reducing the frequency or dose before lab tests, and discuss these medications with your doctor as corticosteroids are known to reduce TSH levels.
  • Reduce caffeine and nicotine use before thyroid tests. Do not drink alcohol the night before a lab draw.  Caffeine and alcohol can stimulate sympathetic pathways which can affect TSH release.
  • Be aware that biotin can falsely elevate T4 levels, especially free T4 levels, so avoid multivitamins for at least one day and the morning of a lab draw.

Consider increasing thyroid awareness by sharing this post, joining the thyroid forum, or signing up for the newsletter!  https://www.thyroidcode.org/thyroid-forum/

 

References

  1. Braverman and Cooper (2013). Werner & Ingbar’s The Thyroid, A Fundamental and Clinical Text, 10th ed. Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins.
  2. Singer, P. (2009).   Manual of Endocrinology and Metabolism, 4th  Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins: (414-448).
  3. Sheehan, M. T. (2016). “Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed – A Review for Primary Care.” Clinical Medicine & Research 14(2): 83-92.
  4. Chopra, I. J., et al. (1975). “Reciprocal changes in serum concentrations of 3,3′,5-triiodothyronine (T3) in systemic illnesses.” J Clin Endocrinol Metab 41(06): 1043-1049.
  5. Bianco, A. C. and B. W. Kim (2006). “Deiodinases: implications of the local control of thyroid hormone action.” Journal of Clinical Investigation 116(10): 2571-2579.
  6. National Academy of Hypothyroidism (2016). https://www.nahypothyroidism.org/inadequacy-of-thyroid-stimulating-hormone-test/  Accessed 3/2/18.
  7. Continuing Medical Education. Vol 30, No 7 (2012). http://www.cmej.org.za/index.php/cmej/article/view/2515/2432  Accessed 3/2/18.
  8. National Academy of Hypothyroidism (2016). https://www.nahypothyroidism.org/how-accurate-is-tsh-testing/  Accessed 3/2/18.
  9. O’Connor, T. M., et al. (2000). “The stress response and the hypothalamic‐pituitary‐adrenal axis: from molecule to melancholia.” QJM: An International Journal of Medicine 93(6): 323-333.
  10. Shomon, Mary; Very Well (2018).   The Optimal Treatment for Hypothyroidism: Kent Holtorf, MD.  Dr. Kent Holtorf Shares His Approach to Treating an Underactive Thyroid.  Updated February 06, 2018.  https://www.verywell.com/optimal-treatment-for-hypothyroidism-kent-holtorf-md-3233006.  Accessed 3/2/18.

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