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The trouble with TSH (Thyroid Stimulating Hormone), or more specially, with your doctor relying solely on TSH to completely assess thyroid physiology, is that it happens to be extremely complex and sensitive to the influence of many other factors. There are a number of reasons why your doctor’s reliance on this single lab test is incorrect for determining hypothyroidism or any other disease. For you to fully comprehend why you are right and your doctor wrong, you need to understand all the fallacies of using the TSH test to diagnose a thyroid problem. My personal opinion, after running hundreds of comprehensive thyroid panels, is that reliance on this test alone, may be the greatest disservice physicians are doing to their patients today. Let’s explore why this is so and discuss each reason in depth.

1) Incorrect philosophy – There are a number of problems with the philosophy of relying only on lab tests, regardless of which ones, to diagnose whether a patient has hypothyroidism or not. Doctors are supposed to treat patients, not lab tests. Here are a few of the reasons this philosophy is incorrect:

  • No thyroid lab test can determine function of thyroid hormone at the cellular level. None can tell how well thyroid hormone interacts with thyroid receptors on the cell surface or how much it stimulates the mitochondria to produce energy. Only functional tests (Basal Metabolic Temperature and Resting Metabolic Rate tests) can do that.
  • Using lab tests exclusively to diagnose, is apparently what many doctors do today. A patient is not just a set of labs. Patient history, signs, symptoms and examination, along with labs, constitute a diagnosis. If you have multiple symptoms of hypothyroidism- you probably are functionally hypothyroid. (Click here to see how you score on a questionnaire of hypothyroid signs and symptoms).
  • Even assuming that the TSH test is accurate, the philosophy of determining a complex process with a simple test is flawed. The test is capable of determining one thing only- the level of TSH in the blood. Extrapolating this to thyroid function omits the 10 or so steps it takes to get to function at the cellular level.
  • Relying exclusively on TSH as the sole marker for thyroid function, hypothyroidism, etc, automatically assumes that your hypothalamic-pituitary-thyroid (HPT) axis is performing flawlessly. Inherent in that assumption is that nothing can go wrong with that axis and that the problem, if any, must be with your thyroid only. There are many factors that can impact normal HPT function. Some of them are: excess cortisol, inflammation, excess cytokines (IL- 1 beta, IL-6 and TNF-alpha all downregulate the HPT axis), toxicity, iron, iodine or selenium deficiency, neurotransmitter deficiency and autoimmunity.
  • Also fundamental to the philosophy of using TSH is that a hormone several steps removed from the production and release of thyroid hormone, a hormone not even produced in the thyroid gland, is a better assessment of thyroid status than direct measure of thyroid hormones themselves! If TSH and thyroid hormones don’t correlate, most doctors say there is nothing they can do because your TSH is “Normal”. Doesn’t it make sense that if there is a disconnect between TSH and thyroid hormone status, that TSH is a better marker for hypothalamic-pituitary function and thyroid hormones are a better marker for thyroid function?
  • If your doctor tells you that TSH is the only test necessary to evaluate hypothyroidism, then his or her assumption is that the test is foolproof. The logic that would apply is that TSH must be elevated for you to be hypothyroid. Based on this assumption, then the logical conclusion is that whenever TSH were low one must be hyperthyroid. This is clearly not the case as TSH is frequently low, without accompanying hyperthyroidism.

2) Questionable Normal Lab Range – This is a biggie. The TSH test first came out about 1971. The initial upper range was set at 15mIU/L and was based on a small sampling of severely hypothyroid patients. The ranges have continued to change over the years and are now as low as 0.1 and as high as 5.5, depending upon the lab. There are many problems with this range:

  • Does anyone reading this think that one moment you are perfectly healthy and then you suddenly develop a thyroid problem? No, that’s not the way it works, right? There is a gradual progression of the condition. But according to the way your doctor reads your labs, that is just what happens. Kaiser says “normal” for TSH is 0.1-5.5mIU/L. So according to this if you are 0.1 or 5.5, you are fine and both values mean the same thing- you are “Normal”. Now the first thing you may notice is that you can’t get much lower than 0.1. You might also notice that this is a huge range- 55 times or 5,500% between high and low. I would challenge any doctor to find any other lab that has such a huge range. Let’s use an analogy. Let’s say I have a series of 55 rooms and doors between each room, in a line. The rooms start at a temperature of 0 degrees and increase by 2 degrees as you go through each room, so the last room will be 110 degrees. This is a good analogy because this is what thyroid hormone does- it increases your metabolic rate or temperature. I think we can all agree that neither 0 nor 110 are very pleasant and that we would do much better in the middle. Can we also agree that 0 degrees is very much different than 110 degrees and that the living conditions in each room would be very different? Don’t you also think the condition of your body is different at each temperature and that 0.1 is NOT the same as 5.5?
  • It’s really important for you to understand lab values and how your doctor interprets them. The lab sets what they call “Normal Ranges” using a statistical tool. The statistics don’t matter, but what this does is to create a bell shaped curve where, by definition, 95% of the population is considered normal. Now this is something the lab sets, not your doctor, but for some reason, your doctor accepts a statistical tool from the lab, who doesn’t know you as a person or patient, and he or she scans down the sheet of labs, looking for red flags that the lab puts on the report. No red flags, no problem. Your doctor doesn’t look at each individual lab test to see if it might be borderline or not. Let’s see if this makes any sense. So what they are saying is that the only abnormal on the low side is if you essentially don’t have any TSH at all. Does that make sense? Now remember I said that by definition only 2.5% of the population is low and 2.5% high. So according to this logic for you to be clinically hypothyroid and be diagnosed with hypothyroidism you have to have a TSH above 5.5, if you are a Kaiser patient. So magically, only 2.5% of the population can be hypothyroid- right? So how is it that somewhere between 6-8% of the population has Hashimoto’s and that according to Dr. David Brownstein, Dr. Broda Barnes and Dr. Mark Starr (all authorities and authors of thyroid books), up to 40% of the population may be subclinically hypothyroid? In 2000, the Colorado Thyroid Disease Prevalence Study concluded that 9.5% of a huge study population of over 25,000 people had elevated TSH levels above 5.1mIU/L. Is it beginning to sound like you may have been told your thyroid is fine, but you now think otherwise?
  • TSH is more than just a marker for hypothyroidism. It turns out that TSH levels within the “normal” range is an independent risk factor for elevated cholesterol and triglyceride levels, and therefore for increased risk of cardiovascular disease. A study of 406 people with normal thyroid function and who had been recently diagnosed with asymptomatic coronary heart disease (CHD) were studied. They found that people whose TSH levels above 1.0 had higher cholesterol, LDL cholesterol and triglycerides (TGA). There was a linear relationship between TSH, cholesterol, LDL and TGA. Another study of 310 women showed that TSH levels above 3.13 were associated with a significantly higher prevalence of diabetes and TGA levels. Higher TSH levels above 2.3 were associated with increased arteriosclerotic plaque in the carotid arteries and thickness of the walls of the carotid arteries. The obvious conclusion is that TSH levels well within today’s lab normals are positively associated with cardiovascular disease.
  • Lack of consistency in establishing “Normal” values: Different expert organizations recommend different reference ranges. The National Academy of Clinical Biochemistry has proposed lowering the upper limit of normal to 2.5 or even as low as 2.0. Another study, NHANES III, found normal values as low as 3.24.
  • The values used by F/M practitioners are much narrower. We use a range of 1.8 to 3.0 for TSH. The difference between the low and high is less than 200% vs. 5,500% if you are a Kaiser patient. Which do you think will be better at detecting an early or subclinical problem before it gets out of hand?
  • TSH values are highly sensitive to minor changes in serum free T4. However it is free T3 inside cells (not outside as in the serum) that is the major metabolically active hormone.
  • Time of day lab was done: TSH values vary by up to 50% of the mean value throughout the day, tending to be lowest in the afternoon and highest at night.
  • TSH values increase with age, however there is no age-related adjustment made by the lab.

“For every complex problem, there is a simple solution – and it’s wrong”.   –H.L. Mencken

3) Drugs that Suppress TSH- A number of drugs suppress TSH production, so that a false negative may occur. Here is a list of some:

  • Glucocorticoids (Steroids): Suppress Thyroid Releasing Hormone (TRH), thereby reducing TSH
  • Dopamine Agonists (Drugs that treat Parkinson’s, restless leg syndrome, and depression): reduces the amplitude of TSH pulses.
  • Somatostatin analogs: (Drugs for treatment of Acromegaly and certain neuroendocrine tumors): Somatostatin is an inhibitory neuropeptide secreted by the hypothalamus.
  • Rexinoids (Drugs that act on hormone receptors in the nucleus of cells. They are a sub-class of Vitamin A. Used for treatment of various cancers): Inhibits TSH transcription in the pituitary and increases breakdown of thyroid hormone in cells.

Not only will glucocorticoid drugs suppress TSH, but also cortisol, a glucocorticoid produced by the adrenal glands, when in excess, can have the same effect. Stress can significantly increase cortisol. Somatostatin is a hormone produced in the stomach, pancreas and hypothalamus. High levels of insulin stimulate Somatostatin release, which then acts to reduce insulin levels, so insulin resistance may increase Somatostatin and reduce TSH. If you have metabolic syndrome or diabetes Type 2, you may be inhibiting release of TSH.

4) Deiodinase enzymes and TSH- T4, the major thyroid hormone produced in the thyroid gland, must be converted to T3 to be active in the peripheral tissues. There is a set of three enzymes, called deiodinases (called D1, D2 and D3), which accomplish this. D1 and D3 enzymes are dependent upon the trace element selenium, which acts as a cofactor, to function properly.

A 2015 paper from the National Academy of Hypothyroidism explains how deiodinases exert local control over thyroid at the cellular level and discusses the many factors that can alter those levels without affecting TSH. Their summary states “With an improved understanding of thyroid physiology that includes the local control of intracellular activation and deactivation of thyroid hormones by deiodinases, it becomes clear that standard thyroid tests often do not reflect the thyroid status in the tissues of the body, other than the pituitary. This is especially true with physiologic and emotional stress, depression, dieting, obesity, leptin and insulin resistance, diabetes, chronic fatigue syndrome and fibromyalgia, inflammation, autoimmune disease, or systemic illness. Consequently, it is inappropriate to rely on a normal or low TSH as an adequate or sensitive indicator of normal or low tissue levels of T3 in the presence of any such conditions, making the TSH a poor marker for the body’s overall thyroid level. In order to be appropriately and thoroughly evaluated for thyroid dysfunction and obtain optimal treatment, it is important that patients find a thyroidologist who understands the limitations of standard thyroid testing and can clinically evaluate patients by taking an extensive inventory of potential signs and symptoms that may be due to low tissue thyroid levels despite normal standard thyroid tests. The free T3/reverse T3 ratio can be valuable in evaluating potential deiodinase dysregulation and measuring the speed of the relaxation phase of the muscle reflex, and the basal metabolic rate can also be helpful additions in the evaluation of tissue thyroid levels”.

They continue by stating, “Thyroid stimulating hormone (TSH) is produced in the pituitary and is regulated by intra-pituitary T3 levels, which often does not correlate or provide an accurate indicator of T3 levels in the rest of the body. Using the TSH as an indicator for the body’s overall thyroid status assumes that the T3 levels in the pituitary directly correlate with that of other tissues in the body and that changes directly correlate with that of T3 in other tissue of the body under a wide range of physiologic conditions. This, however, is shown not to be the case; the pituitary is different than every other tissue in the body. Due to a unique make-up of deiodinases in the pituitary, it will respond differently and often opposite to that of every other tissue in the body. Numerous conditions result in an increase in pituitary T3 levels while simultaneously suppressing cellular T3 levels in the rest of the body, making the pituitary, and thus the TSH, a poor indicator for tissue thyroid levels in the rest of the body under numerous physiologic conditions. In addition to having a unique make-up of deiodinases, the pituitary also contains unique membrane thyroid transporters and thyroid receptors. As opposed to the rest of the body that is regulated by both D1 and D3, the pituitary contains little D1 and no D3; so pituitary T3 levels are determined by D2 activity, which is 1000 times more efficient at converting T4 to T3 than the D1 enzyme present in the rest of the body and is much less sensitive to suppression by toxins and medications. In the pituitary, 80-90% of T4 is converted to T3 while only about 30-50% of T4 in the peripheral tissue is converted to active T3. This is due to the inefficiency of D1 and the presence of D3 in all tissues of the body except the pituitary that competes with D1 and converts T4 to reverse T3’.

Another study showed that a selenium, but not an iodine deficiency significantly decreased Type 1 deiodinase activity to only 6-13% that of controls, meaning a significant reduction in the conversion of T4 to T3. At the same time, Type II deiodinase, found in the brain and pituitary gland was not significantly affected, indicating that it may possibly not be dependent on selenium. The importance of this is that with a selenium deficiency, peripheral conversion of T4 into T3 will be affected, but conversion in the pituitary will continue as normal. This would then mean that despite reduced peripheral T3, that TSH levels would not increase, as TSH is sensitive to the levels of T3 within the pituitary.

5) Leptin – Leptin is a hormone that regulates weight and metabolism. It signals the brain when there are sufficient fat stores by increasing its secretion. When leptin resistance is not present and the hypothalamus is functioning normally, it stimulates metabolic processes resulting in weight loss and satiety (reduction in hunger and an increase in lipolysis (fat breakdown). Unfortunately leptin signaling malfunctions in most overweight and obese people, as well as those with metabolic syndrome and diabetes. It is often found in conjunction with insulin resistance. These individuals suffer from leptin resistance, which makes it significantly harder to lose weight. Leptin resistance is perceived as starvation, so fat stores actually increase, rather than decrease as would normally occur if leptin signaling were properly functioning. Leptin resistance affects TSH levels by suppressing D1 and stimulating D2, leading to decreased cellular T3 while also decreasing serum TSH. Elevated rT3 makes the situation worse.