Hypothyroidism: Revealing The Truth About Testing

Hopefully, most of you have read the book by Elle Russ, “Paleo Thyroid Solution” (1st ed 2016, 2nd ed 2020), as I have a published interview that adds to her excellent work. This book details the ways to treat hypothyroidism and autoimmune thyroid disease. Her work runs counter to the inaccurate and harmful advice of the vast majority of Western endocrinologists and internists who have a profoundly simplistic and dangerous approach to treating hypothyroidism.

This book provides lifesaving advice on the right way to diagnose and treat hypothyroidism, and the most common cause for this diagnosis, autoimmune thyroid disease, often called Hashimoto’s thyroiditis or Hashimoto’s Disease. I will focus today on accurately treating hypothyroidism regardless of the underlying cause and not on treating autoimmunity.

As an educated doctor on treating hypothyroidism, I still lose patients to “specialists”, whether they be actual endocrinologists or someone with a blog or podcast; neither group seems to care to research thyroid physiology. I do.

What follows will be somewhat dense, a referenced article on thyroid treatment and testing. This is for any thyroid patient to share with their provider in the hope that they will listen. Most doctors who accept in-network insurance payments don’t have the time or energy to research and treat beyond what they learned in residency. They are taught currently to order as few tests as possible, especially if they are part of an HMO. It is difficult, but not impossible, for them to learn more. Be gentle in your approach to them if you hope to help them, and yourself. I, however, do not have to be gentle, so the gloves come off today.

Thyroid Hormone Therapies

Levothyroxine - tetraiodo- L-thyronine (T4)- generics available - Brands include Synthroid, Levoxyl, and for sensitive individuals Tirosint. Compounding pharmacists can create doses between the tablets dispensed through your pharmacy as well, with or without T3. The “storage” form of thyroxine with a stable half life of 7 days! Provides a stable reservoir for your body to draw from but has little function on its own.

Liothyronine - triiodo-L-thyronine (T3)- generics available- Brand name Cytomel. Compounding pharmacies can create individualized prescriptions of immediate release and sustained release T3.  Unlike when you take prescription T3, your own body requires 5’ deiodinase to convert T4 to T3 by removing an iodine, thus activating your T4 thyroid hormone if acted on by Deiodinase 1 (D1) located primarily in the thyroid, liver and kidney or Deiodinase 2 (D2) primarily located in the hypothalamus, pituitary and brown fat. Please note and emphasize that the hypothalamus and pituitary have a separate enzyme than the rest of your body for regulating T4 to T3 conversion. Please also note that the pituitary regulation of Thyroid Stimulating Hormone (TSH) cannot accurately predict thyroid function in the body as T3 in the body has a separate regulatory enzyme. Please also note that TSH is not a thyroid hormone! It is a pituitary hormone “looking” at your thyroid function.

In “Single Dose T3 Administration: Kinetics and Effects on Biochemical and Physiologic Parameters” PMID 24977379 we see peaks of T3 at 2.5 hours, a peak heart rate increase at 5 hours, yet TSH suppression that lasts 2-3 days, all with one dose! The levels of T3 return to baseline by 12 hours, the half life is approximately 4-6 hours, the physiologic half life that people talk about as 2.5 days refers to TSH suppression only.

Every doctor who has even an inkling of knowledge about thyroid hormone physiology understands that the not-a-thyroid-but-a-pituitary hormone TSH can not be used to monitor any hypothyroid patient treated with T3! See appropriate tests below.

Natural Desiccated Thyroid (NDT) or dried porcine thyroid, the most commonly available FDA - regulated prescriptions include NP Thyroid and Armour Thyroid, NatureThroid is no longer available. A 60 mg dose of NDT contains 38 mcg T4 and 9 mcg T3. This 4.2:1 ratio is the same ratio that human thyroid secretion occurs. NDT also contains two hormones T2 and T1 that are deactivated thyroid hormones, whether this is good or bad is debatable.

When your doctor is trying to mimic a more natural thyroid hormone replacement they will always look to NDT as one of the options, one that we have used for over 100 years now.

T4 and T3 combinations and T3 only prescriptions:

This can be accomplished via existing available medicines, or through help with your compounding pharmacist. It has been known for decades that clinical response is better when these hormones are used in combination, just the way your thyroid does it!

In: Escobar-Morreale HF, Botella-Carretero JI, Gómez-Bueno M, Galán JM, Barrios V, Sancho J. Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med. 2005 Mar 15;142(6):412-24. doi: 10.7326/0003-4819-142-6-200503150-00007. PMID: 15767619. We found an article that mimics my clinical results almost identically although the treatment options were limited and they did not measure the RT3 (more on this coming up). When 28 women were asked in a randomized double-blind crossover trial whether they preferred, due to symptom relief, 100mcg T4 vs 75 mcg T4 plus 5 mcg T3 or 87.5 mcg T4 plus 7.5 mcg T3, 12 patients preferred 75/5, 6 patients preferred 87.5/7.5, 2 patient preferred 100mcgT4 only and 6 patients had no preference. In this very limited trial 18 of 26 patients who completed the trial preferred combination therapy. On average TSH was decreased by 0.85 mU/L and free T3 was increased by 0.8 pmol/L. As expected 10 patients had TSH below the reference range.

What confused the researchers is that they couldn’t figure out why so many patients felt better (women -think misogyny in medicine here, and how feeling better, especially if a woman, doesn’t matter), that, along with a (truly unimportant) decrease in TSH kept this from being accepted as the landmark study which it truly was. People prefer combination therapy, they just didn’t know their lives also depend on it.

Thyroid Hormone Tests

You can not effectively measure someone’s thyroid functions without the TSH, Free T4, FreeT3 and Reverse T3. The free T3 and reverse T3 are, by far, the most important tests yet are not measured by standard primary care doctors and endocrinologists . This is because of a pervasive misogyny in medicine and a medical system supplicant to Big Pharma who wishes only the highest profit medicine remains (Synthroid), while creating untold misery, suffering, and disease that can then be treated by other pharmaceuticals. See below, the low free T3 and high reverse T3, seen  on T4 only therapy,when you measure it, is profoundly associated with all-cause mortality.

Thyroid Stimulating Hormone (TSH): This was the first laboratory test (1975) available to physicians, prior to this we focused on symptoms and the symptomatic response to NDT. It was a breakthrough for its time and as we near the half century mark of this test, it is time for a serious upgrade! 

As stated above, it is the shadowy reflection of what your hypothalamus and pituitary, based on a separate D2 system, “thinks” what might possibly be going on in your body in regard to thyroid function. It is not a thyroid hormone and can’t be utilized effectively to monitor thyroid as far better tests exist.

The clinging to the past, nostalgic, “this is the way we used to do it” approach to medicine has no place when far superior tests have become available. It is also through the misinterpretation, meaning wrong interpretation, of past trials that has endocrinologists puckering their collective anal sphincters over this test. They believe, inaccurately, that suppressed TSH, due to therapies with T3, causes osteoporosis.

Please note, firstly, that the reference range for TSH is based on people without hypothyroidism. If a doctor uses T4 only in their practice, due to its prolonged half life, makes the TSH test of some use when you are on T4 only therapy.

In regards to bone density I will list a variety of references you or your doctor can look up:

1. “Lack of Deleterious Effect on Bone Mineral Density of Long-Term Suppressive Thyroxine Therapy For Differentiated Thyroid Carcinoma 2005 PMID 16322336 After thyroid cancer we intentionally suppress TSH with thyroid hormone for 10 years and more sometimes. Conclusion: No changes in the bone breakdown marker Urinary N Telopeptide (UNTx - a test every woman who suspects bone density issues exist, independent of thyroid status, should get) or bone density occurred! Conclusion: Long term suppressive T4 treatment does not affect skeletal integrity.
2. “Skeletal Integrity in Men Chronically Treated With Suppressive doses of L-Thyroxine” 1997 PMID 9240728 Following 34 men with suppressed TSH to treat a variety of conditions, average dose of T4 a hefty 172 mcg per day treated for an average of 10 years showed no changes in bone density compared to age matched controls. Conclusion, suppressive thyroid hormone therapy doesn’t affect men either.
3. “The effect of Levothyroxine Therapy on Bone Mineral Density: A Systematic review of The Literature. 2003 PMID 14714266 In a rousing review of 63 studies on suppressive levothyroxine therapy 31 showed no effects, 23 showed partial beneficial or mixed results, and 9 studies showed overall adverse effects. 

Interestingly, the last meta-analysis confirms my clinical experience that women with the lowest TSH test always seem to have the best bone density! More importantly, if you ever get placed on thyroid medicine and are worried about your bone density, you can measure the UNTx, and you no longer have to wonder or worry about your bone health, you measure it!

Hopefully I will never have to talk about TSH and bone density again. It has been settled for decades that suppressing TSH does not cause bone loss.

What about cardiac status and TSH suppression? This is the other, more valid argument, about appropriate thyroid hormone therapy. I will focus on the upcoming thyroid tests as we discuss cardiovascular mortality. My clinical experience matches the article above on the kinetics of T3 therapy. When you give 50mcg T3 (usual dosage 5-10 mcg) the average heart rate increases by 18 beats per minute,which is quite significant. Thus, if you give more T3 than is necessary you can cause tachycardia, and possibly exacerbate an underlying arrhythmia. Everybody has an IWatch these days and the ability to monitor their heart rate. Teach yourself and anyone with any form of thyroid therapy, T3 has dramatic benefits, but too much T3 does not, however decisions about T3 are based on your symptoms and heart monitoring, and not on TSH!

One last note on TSH, I have seen hundreds if not thousands of patients inappropriately begun on thyroid hormone therapy (always T4) based on a mild elevation of TSH, which can be an early sign of hypothyroidism, none of these patients notice a benefit to the treatment. The TSH will go lower and your physician thinks they win! The physician inevitably increases your dosage and suppresses your natural thyroid function,but you inevitably end up profoundly hypothyroid with a low free T3 and a high reverse T3, the tests they refuse to measure, while making you profoundly unwell and diseased.

Free T4- Free Thyroxine

The second most common test, having adequate T4 is a great reservoir for conversion to the active thyroid hormone T3. A mildly useful test, at least you are measuring thyroid hormones now!

Free T3 - Free Triiodothyronine

The single most important thyroid test when combined with RT3. This is the primary circulating thyroid hormone with regards to activity, regulation also occurs based upon interaction with the nuclear T3 receptors, and so many studies indicate that the plethora of Endocrine Disrupting Chemicals (EDCs are decreased by living an organic lifestyle) in our environment affect actual effects of T3 with the nucleus of our cells. I do think our toxic environment has had a profoundly negative effect on D1 and D2, as well as nuclear receptor thyroid regulation, all making low T3 so profoundly common.All I can tell you is keeping a free T3 above 3.0 (pg/ml) seems to be our most important thyroid test, depending on concurrent RT3 levels. A few studies:

“Low-T3 Syndrome: A Strong Predictor of Death in Patients With Heart Disease” 2003 PMID 12578873. Low free T3 (< 3.1 ) in patients with known CAD (followed for only one year)suffered a 14.4% (7.5% cardiac) overall mortality 3 % (1.5% cardiac)in those with a normal free T3 >3.0. This was, by far, the single most important predictor of mortality, not lipids, or even heart function.

‘Serum T3 level can predict cardiovascular events and all-cause mortality in CKD (Chronic Kidney Disease) with Proteinuria 2012 PMID 22260378. Simply documents how low T3 dramatically increases all cause mortality.

In my practice the importance of T3 as part of therapy is more about feeling well in the here and the now, fortunately if I actually care about mortality and cardiovascular health I measure free T3 and don’t care at all about TSH, I care about the patient.

Reverse T3 (RT3):

When T4 is acted on by 5’ deiodinase type III (D3) present ubiquitously in the body, T4 is inactivated into RT3. RT3 blocks the T3 receptor more than it is “anti-thyroid” as I have heard it called. Short term this can actually save our lives when dealing with hyperthyroidism, but is more commonly found under prolonged psychological or physical stress or due to inappropriate T4 prescriptions.

Think of high RT3 ( above 15 ng/dl, also depends of FT3) as a way your body has to slow down your metabolism. If you are facing a famine or hyperthyroidism, increased RT3 is good. But elevations hopefully will be transient. As you shall see below:

“Reverse T3 In Affective Disorders 1983” PMID 6417704

“A significant increase in RT3 and a significant decrease in T3 levels, but no significant difference in T4 or TSH levels (this was before free hormone testing), were seen in the patients with the most pronounced clinical symptoms as measured by the Comprehensive Psychopathological Rating Scale.” 

My commentary, when you correct Free T3 and reverse T3 problems, refractory depression, brain fog, and memory dysfunction can melt away. And, yes, this has been known for 40 years.

“Action of Reverse T3 on Cancer Cells” 2019 PMID 30943372 RT3 increases the proliferation in vitro of human breast cancer and glioblastoma (brain cancer) by 50-80%! Conclusion: RT3 may be a host factor supporting cancer growth.

Gone are the days when doctors could intentionally inflict harm by not measuring free T3 and reverse T3. Although the American Association of Clinical Endocrinology fights against the use of these tests, that is due to them protecting their own interests after decades of malevolent neglect.

I am tired of playing nice; it is just not a leap that we must measure thyroid tests to adequately diagnose and treat hypothyroidism. That better tests than the TSH have existed for 40 years, and doctors refuse to order them, then proceed to prescribe inadequate therapies that are killing you, then convincing you that, when they haven’t measured your thyroid hormone metabolism, that the TSH being low means anything, is simply criminal at this point.

Don’t stand for it.

Gary E Foresman, MD