Hypothyroidism Redefined

Topic: Hypothyroidism; Reverse T3; Levothyroxine

Last update: 08-18-22

By Eugene Heyden, RN

Approximately a decade ago I wrote a “scholarly” paper, outlining my discoveries into the nature of hypothyroidism.  It was written primarily for the physician (lots of doctor talk), but you can read it if you want.  (To access, click on the link below.)  My motivation in all this, is to tell a story that is not being told.  It is the story of a form of hypothyroidism that occurs at the tissue and cell level, a form of hypothyroidism that exists when typical thyroid function test are completely normal.  It automatically occurs from the standard treatment of hypothyroidism and can go completely unnoticed and go uncorrected for a lifetime.  The story also includes a strategy to address this form of hypothyroidism.

There is a good reason why I undertook this study.  I was confronted with an array of symptoms exhibited by a close family member, symptoms that closely resembled hypothyroidism; yet, standard testing said, in effect, “No hyperthyroidism here!”   Something about this “verdict” did not seem quite right, so I decided to look into things a little further.  Actually, it was a relentless study of the research literature, and only took ten years.

So what is this “untold” story?  Briefly: Hypothyroidism is not what you think.  True, it results from a failure of the thyroid gland to produce sufficient quantiles of thyroid hormone, a deficiency that can be identified by standard laboratory testing.  But, as I write in the paper, “Although hypothyroidism can certainly be defined by abnormal thyroid hormone levels, hypothyroidism can best be characterized by thyroid hormone levels at the cellular level that are not appropriate for the individual.”  And here is the problem with the standard thyroid replacement: it creates and sustains a subtle form of hypothyroidism at the tissue and cellular level.  Surprisingly, an individual still has hypothyroidism even though they are treated for hypothyroidism!  Crazy, I know!  The thyroid function tests may become normal with treatment, but the disease is converted into something else, it is converted to hypothyroidism at the tissue and cell level.  If this treated hypothyroidism patient is you, you now have a subtle form of hypothyroidism that is somehow acceptable and allowed to continue.  You may be “all better” with thyroid hormone replacement, but maybe not.  Could it be that this subtle form of hypothyroidism is behind symptoms that persist?

So here’s the deal: In the treatment of hypothyroidism, T4 (e.g., Synthroid, levothyroxine, Levoxyl) is almost universally given.  Although a normal thyroid gland releases both T4 and another hormone called T3, about 80% T4 and about 20% T3, it is generally believed that only T4 replacement is required to correct hypothyroidism.  According to the operating theory, the T4 will be metabolize in various cells of the body to create and release enough T3 to meet individual need.  And things should be all right.  The problem is:

“Substitution of thyroid hormone with LT4 [T4] in patients with primary hypothyroidism, when titrated to normalize serum T4, results in a mean serum T3 level that is lower than normal.  However, when T4 is administered in amounts to normalize T3, T4 parameters will rise to supranormal concentrations.”  ~Hennemann et al., 2004, emphasis added

As indicated above, there are a couple of things wrong with the standard, T4-only therapy for hypothyroidism.  Firstly, the T3 level really never returns to normal.  In fact, it is about 20% lower than it should be (Escobar-Morreale et al., 1996).  And secondly, in order to supposedly correct hypothyroidism, T4 has to be given in a dose that raises its concentrations well above normal.  And consider this:

“Finally, the dose of T4 needed to ensure a normal T3 concentration (and presumably, euthyroidism) [normal thyroid status] is not the same in all tissues.  It is evident that even if the undesirable effects of excessive T4 concentrations were disregarded, peripheral conversion of T4 to T3 did not fully compensate for the absence of thyroidal secretion of T3.” ~Escobar-Morreale et al., 1996, emphasis added

The result of all this?  Hypothyroidism isn’t really corrected at all.  It is just changed in form.  It is now an abnormality occurring at the tissue and cell level.  Hypothyroidism becomes hypothyroidism, hypothyroidism at the tissue and cell level.

“It is evident that even if the undesirable effects of excessive T4 concentrations were disregarded, peripheral conversion of T4 to T3 did not fully compensate for the absence of thyroidal secretion of T3.”  ~Escobar-Morreale et al., 1996, emphasis added 

So, why not compensate for the absence or limitation of thyroidal T3 output?  We could do this, but we don’t.  And we don’t do this because of the time-honored belief that T4 only is the best course of action to take.  But the evidence says otherwise.  Fortunately, there is a physiological course of action to take.

“In all these studies T3 was used in the plain form that results in non-physiologic serum T3 peaks.  In these studies, it is suggested that substitution with T3 should preferably be performed with a preparation that slowly releases T3 to avoid these peaks.  In the study reported here we show that treatment of hypothyroid subjects with a combination of T4 plus slow-release T3 leads to a considerable improvement of serum T4 and T3 values, the T4/T3 ratio and serum TSH as compared to treatment with T4 alone.”   ~Hennemann et al., 2004, emphasis added

The bottom line in all this, is we should do things different in our treatment of hypothyroidism.  We should try to mimic the T3 and T4 output in a ratio that normally occurs in a healthy thyroid gland.  We resist the urge to prescribe T3 in its rapid-release, normal form (Cytomel).  We give it in a slow-release form (think compounding pharmacy).  And there is one more thing we do.  We take care not to give too much T4 in the treatment of hypothyroidism.  Away with giving T4 in “supranormal” amounts!

Sure, in all this, the physician can fly by the seat of his or her pants.  Or he or she can order a readily available test called the reverse T3 (rT3) level.  And why would anyone want to order a test that determines the level of a so-called “inactive hormone?”  The physician can use this test to make sure T4 is not given in excess.  The body defends against T4 excess by turning a good portion of it into rT3, taking molecule after molecule of T4 promptly out of existence.  This translates into elevated rT3 levels and signals that T4 is being given in excess.  It is this test, rT3, and a calculated ratio between it and fT3 (free T3)—not the TSH—that reveals what is occurring at the tissue and cell level.

“The T3/rT3 ratio is considered to be a sensitive indicator of the peripheral metabolism of thyroid hormone, being positively influenced by D1 and D2 and negatively by D3.  This ratio is also relatively independent of thyroidal T4 production and of variations in serum binding proteins.”  ~Peeters et al., 2006, emphasis added

All this is carefully documented in my paper.  Your physician should read it.  You can make it happen.  With a little luck (and the twisting of an arm), you can carve out an opportunity to receive exceptional, not run-of-the-mill care.

 

Click here to read the paper:

Hypothyroidism Redefined (For the Physician)

 

References
Topic: Hypothyroidism; Reverse T3; Levothyroxine

Escobar-Morreale HF, Escobar del Ray F, Obregón MJ, Morraele de Ecsobar G 1996 Only the Combined Treatment with Thyroxine and Triiodithyronine Ensures Euthyroidism in All Tissues of the Thyroidectomized Rat. Endocrinology 137(6):2490–2502

Hennemann G, Docter R, Visser TJ, Postema PT, Krenning EP 2004 Thyroxine Plus Low-Dose, Slow-Release Triiodothyronine Replacement in Hypothyroidism: Proof of Principle. Thyroid 14(4):271–275

Peeters RP, van der Deure WM, Visser TJ 2006 Genetic Variation in Thyroid Hormone Pathway Genes: Polymorphisms in the TSH Receptor and the Iodothyronine Deiodinases. European Journal of Endocrinology 155(5):655–662 https://pubmed.ncbi.nlm.nih.gov/17062880/

 

Disclaimer: This article is presented solely for informational purposes.  The information contained herein should be evaluated for accuracy and validity in the context of opposing data, new information, and the views and recommendations of a qualified healthcare professional, and not to be substituted for professional judgment and guidance or to provide reason to neglect or delay appropriate medical care.  It is the reader and reader only who bears the responsibility for any actions that could be construed as being a response to the information contained herein.  The statements and opinions expressed by the author have not been reviewed or approved by the FDA or by any other authoritative body.  This article is offered to the reader to broaden his or her understanding of the issues discussed and to help identify options that may be suitable for the individual to pursue, on behalf of self or others, under approval and direction of a qualified physician or medical team member.  The author and publisher offer no guarantees of the accuracy or validity of the quotations incorporated into this presentation.

 

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