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Ask Dr. J: Eeny, Meeny, Miny, or Moe: The Pitfalls of Thyroid Lab Testing.

Let's start with one of the most important endocrine glands in the body, the thyroid. It rightfully attracts a large amount of attention in clinics and on lab testing. Why? Because it has system-wide effects. Thus, if there is an issue with the production, peripheral conversion, or nuclear attachment of their thyroid hormones, patients will have multiple complaints, including many non-specific, body-wide ones such as extreme fatigue, brain fog, and depression as thyroid hormone is the thermostat for human's metabolism.

Thyroid issues are extremely common, and their symptoms and signs are also similar to a variety of other hormonal disorders as well. We, as modern health care providers, are lucky enough to be able to employ brilliant lab tests. We must, however, understand how to interpret these lab tests, so they can actually be useful for us and our patients. Our modern standards of diagnosis do not allow us to reveal non-thyroidal illness or NTI. (1) After 30 years of looking at lab tests and the complaints of many patients, I'm convinced that they suffer from NTI, which is a syndrome that is not directly related to the production of T3/T4 by the thyroid gland. Applying new information and knowledge, especially how T4 is processed to either T3 or Reverse T3/RT3, will give us the ability to better understand our patient's lab results and allow us to give our patients treatments that will actually deal with the source of their problems.

When stimulated by thyroid stimulating hormone/TSH from the anterior pituitary gland in response to decreased circulating thyroid hormone leading to decreased negative feedback and TSH release, the thyroid gland releases about 90% T4 (pre-hormone), about 9% T3 (the active, stimulating form of thyroid hormone), about 1% RT3 (an inhibitory version of thyroid hormone), and a smidgen of T2. (2,3)

First off, why would the thyroid gland release a prehormone instead of just making the active T3 form? According to Alan McDaniel, MD, for the same reason Campbell's puts soup in cans instead of steaming hot bowls: it is safer to transport, and it has a long shelf life.

Next, a potentially large issue arises because converting T4 to T3 is not automatic. (4) There are multiple negative scenarios involved that can make this simple transformation from an inactive into an active form of thyroid hormone dysfunctional.

To start with let's look at some of my favorite science: biochemical physiology. Eighty percent of our daily T3 arises from removing the iodine from the 5-locus on the outer ring of T4 by enzyme 5'-de-iodinase or 5' Dl in peripheral tissues. T4 can also become RT3 by removing the iodine from the 5-locus on the inner ring via enzyme 5 (not prime) de-iodinase or 5 Dl. (5)

Reverse T3 acts as an inhibitor by blocking two forms of 5' Dl, Type-2 5' Dl or D2 and Type-1 5' Dl or Dl, from binding to their nuclear receptors. (6-9) Dl converts T4 to T3 throughout the body but is not a significant determinant of pituitary T4 to T3 conversion. D2 is responsible for pituitary conversion of T4 to T3.

RT3 then is inhibiting the increase in metabolism or the calorigenic effect of thyroid hormone. (10) What is directing the body to make less T3 and more RT3: the chronic stress response from multiple areas: (11)

* Physical stress (e.g., injury, Ml, cancer, or CHF),

* Physiological stress (e.g., starvation or hypothermia),

* Psychological stress (e.g., long-term unhappiness in a marriage or students attempting to obtain good enough grades to enter medical school).

In our society, the psychological cause of increased RT3 appears to be one of the primary causes of NTI. (12,13) This altered metabolism of T4 is an adaptive response to make the metabolism conservative and efficient in times of stress. In human's past, this would be a transient affair if attacked by a saber tooth tiger or maybe if the fall harvest was insufficient and there wasn't enough food to make it until the next harvest. In our modern society, this formation of RT3 can persist for years. Now this beautiful adaptive response for saber tooth tigers and meager fall harvests becomes maladaptive. The result is NTI.

We know what to recommend to our patients to decrease their stress level, but let's review what I think are some of the best choices:

* Sleep (7 1/2 - 81/2 Mi hours per night),

* Gentle exercise (30-60 minutes per day such as yoga or walking),

* Meditation or praying,

* Improve the body's ability to respond to stress through adrenal nutrition,

* Diet (dysglycemia can lead to chronic Cortisol release),

* Identifying food allergies/intolerances,

* Limbic breathing, developed by Majid Ali, MD (I described this in a prior article. Please e-mail me for the details. It is simply practiced and has extremely powerful anti-stress results.)

Let's look at a clinical success story pertaining to what I have written above. This patient is a 34-year-old female with an eight-year-old son and four-year-old daughter. She states that she never recovered completely from the birth of her daughter. Her fatigue has become almost unbearable. She wakes up exhausted and somehow makes it through the day to come home, make dinner, try to talk to her husband and kids, and fall asleep. She has multiple other hypothyroid symptoms and signs, but for her the worst were the 80 pounds she had gained since her daughter's birth and a small, palpable goiter. She rates the stress of her work life and home life a 12 out of 10. Her TSH was 2.5, total T4 was 6.2, and free T4 was 0.99. All were within normal limits although TSH is high normal and T4 and free T4 are at the low end of the optimal ranges. Her doctor had not tested for T3 or RT3. Her cholesterol and LDL were mildly elevated, but no other lab values were amiss. She also had multiple Gl symptoms such as chronic constipation, severe bloating after meals, and chronic epigastric pain. She had been offered anti-anxiety drugs and had refused and came to see me as, of course, a last resort.

How can you also explain to patients that their doctors aren't necessarily testing for the relevant lab results, in her case free and total T3 and Reverse T3. Alan McDaniel has an apropos 11th commandment quote: Thou shalt not look at a normal lab result and tell your patient: "There is nothing wrong with you." Remember: It is accurate to state: "This test doesn't show what is wrong with you."

We had a long conversation about the thyroid gland and how chronic stress can lead to NTI which isn't diagnosable by regular lab testing. I gave her several options to decrease her stress. She chose 30 minutes of walking at lunchtime and to limbic breathe whenever she found herself breathing shallowly.

I also used NAET to test for food allergies and found her allergic to only wheat and citrus. She reported that she sometimes drank orange juice but craved bread, donuts, cookies, etc. and ate them several times per day. She was committed and said she would start to follow a non-gluten diet.

She returned in two weeks with an extremely mild improvement but basically said she had not been able to implement either the dietary or stress changes. She just did not have the energy to add any other routine to her life. I asked her what she really wanted to have happen. Without hesitation, she said to lose the 80 pounds. I was silent; and after what seemed like an eternity, she looked at me and said, "I'll do it." I love it when my patients finally figure out that they have the power to succeed.

She returned a month later and appeared to have had a nice transformation. She had lost eight pounds, had twice as much energy, and she reported that she didn't feel a tightness in her anterior neck area. I palpated, and her goiter appeared to be gone. (I'll admit I'm not the best thyroid palpator, but the goiter was either greatly reduced or gone.) She reported she had successfully stopped eating all gluten and had developed the ability to detect when she was breathing shallowly and to limbic breathe. She was able to limbic breathe at work or at home when she found herself breathing shallowly.

I find it extremely exhilarating when a patient really does the leg work from my recommendations. Success or failure really does boil down to convincing them to actually implement your suggestions. If you can accomplish this feat, it's a win/win scenario. Their health will improve, and their confidence in their ability to succeed will shoot through the roof.

This brings be to my last point. Majid Ali, MD, has written numerous books that are intellectually stimulating. One book is The Ghoraa and Limbic Exercise. In it he talks about limbic exercise and limbic breathing. Basically, he is talking about not letting our conscious cerebral cortex (what he calls the cortical monkey) interfere with our autonomic nervous system (what he calls the limbic dog.) so that our bodies are able to harmoniously function as a unit. I'm going to take Dr. Ali one step further. Basically, this is what I attempt to tell my physiology students and my patients: "Your body is smarter than you. Don't get in its way, meaning don't allow the cortical monkey to stress yourself to disease. In other words, live limbicly!"

Addendum: I quoted Alan McDaniel twice today. He has written for the Townsend Letter in the past. I am extremely fortunate to have access to rough chapters for his book on functional endocrinology. Now, in my estimation, Alan is the Michael Jordan of functional endocrinologists. The applicable clinical knowledge in these chapters is absolutely stunning, and several of my friends will concur who have read his thyroid and adrenal chapters. This information needs to be made available for two reasons: it will dramatically increase our knowledge of clinically relevant endocrinology, and it will allow us to, then, much better serve our patients! I feel Alan could use some help editing and proofreading his chapters. If you feel so inclined, please e-mail me or Dr. Collin for Alan's e-mail and help shepherd an extremely valuable resource into publication.


(1.) DeGroot U. The Non-Thyroidal Illness Syndrome. February 1, 2015. https:/

(2.) Chopra IJ. An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man. J Clin Invest. 1976; 58:32-40.

(3.) Bianco AC, et al. Biochemistry, Cellular and Molecular Biology, and Physiological Roles of the lodothyronine Selenodeiodinases. Endocr Rev. 2002; 23:38-89

(4.) Chopra IJ. A Radioimmunoassay for Measurement of 3,3',5'-Triiodothyronine (reverse T3). J Clin Invest. 1974;54:583-92

(5.) Surks Ml, et al. Determination of lodothyronine Absorption and Conversion of L-Thyroxine (T4) to (L-Triiodothyronine (T3) using Turnover Rate Techniques. J Clin Invest. 1973;52:805-11

(6.) Cettour-Rose P, et al. Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induce inhibition of thyrotropin secretion in hypothyroid rats. Eur J Endocrinol. 2005; 153:429-34

(7.) Branco M, et al. 3,5,3'-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity. Am J Physiol. 1999; 276(1 Pt l):E179-87

(8.) Zhu Bo, et al. Catalysis leads to posttranslational inactivation of the type 1 deiodinase and alters its conformation. J Endocrinol. 2012; 214:87-94

(9.) St Germain DL, Croteau W. Ligand-induced inactivation of type I iodothyronine 5'-deiodinase: protection by propylthiouracil in vivo and reversibility in vitro. Endocrinology. 1989; 125:2735-44.

(10.) Pitman CS, Barker SB. Inhibition of thyroxine action by 3,3',5'-triiodothyronine. Endocrinol. 1959;64:466-8

(11.) Kelly GS, Peripheral metabolism of thyroid hormones: a review. Altern Med Rev. 2000; 5:306-33.

(12.) Opstad K. Orcadian rhythm of hormones is extinguished during prolonged physical stress, sleep and energy deficiency in young men. Eur J Endocrinol 1994;131:56-66.

(13.) Johansson G, Laakso ML, Karonen SL, Peder M. Examination stress affects plasma levels of TSH and thyroid hormones differently in females and males. Psychosom Med 1987;49:390-396

by Jim Cross, ND, LAc thiasl

Jim Cross graduated with a degree in Biology from the University of California at Davis in 1975, and with a secondary teaching credential in life science from California State University, Sacramento, in 1976. After beginning to study naturopathic medicine at Pacific College of Naturopathic Medicine in tiny Monte Rio, California, he finished his naturopathic studies at National College of Natural Medicine in Portland, Oregon, in 1984. He later earned his LAc at San Francisco College of Acupuncture in 1989. He has practiced acupuncture and naturopathy in the Northern Sierra town of Quincy since 1990. He has also taught anatomy and physiology at Feather River College in Quincy since moving there.
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Author:Cross, Jim
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Date:Jan 1, 2018
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