Before reading this blog, you should familiarize yourself with the basic issues regarding lab testing for, and interpretation of Thyroid Stimulating Hormone (TSH)
In Part 1 (Click Here to read), I discussed how frequently doctors mis-diagnose (or more accurately fail to diagnose) hypothyroidism because they rely on only one test for thyroid function, TSH. This is a basic test, not of thyroid function, rather of function of the pituitary gland in the brain. TSH is a brain hormone, not a thyroid one. A basic thyroid panel consists of 9 tests. In my experience, there is little correlation between TSH levels and those of the main active thyroid hormone, free T3.
In Part 2 (Click Here to read) I discussed in depth five major reasons why relying only on TSH to determine thyroid function is totally wrong, including:
- Flawed philosophy- I discuss 6 reasons why assuming TSH properly and thoroughly evaluates thyroid function is incorrect
- There are at least 11 arguments as to why current lab ranges are wrong
- There are a number of drugs that suppress TSH, leading to incorrect readings
- There may be issues with deiodinase enzymes that convert T4 into active T3
- Leptin is a hormone infrequently tested. Elevated levels or leptin resistance decreases TSH
In summary, my first two blogs should make it very clear that TSH is not an accurate predictor of thyroid function at the cellular level. But wait- it gets worse! The reality is that your doctor is only looking for elevated levels of TSH, and pays no attention to low levels. Before proceeding further, it is important to understand the relationship between TSH and the major thyroid hormones T4 and T3, so a basic lesson in thyroid endocrinology is necessary.
TSH, made in the pituitary gland, is produced (when everything is working as it is supposed to), in response to low thyroid hormone levels. It travels to the thyroid gland (and elsewhere- more on this later), where basically it kicks the thyroid into action to make more thyroid hormones. These then travel back to the pituitary to tell it that the gland got the message to make more hormones, and that it can decrease how much TSH it makes. This is called a negative feedback loop. End of lesson.
When one is placed on thyroid hormone replacement, usually with synthetic T4, it suppresses the normal production of TSH. The problem is that often TSH is dramatically decreased, often to or below “normal” levels. This happens even though the levels of T4 and T3 hormones are not elevated above the lab normal values. The obvious result is that there is now a disconnect in the negative feedback system discussed above. So what?
Here’s what. Another brain gland that sits above the pituitary is called the hypothalamus. It produces another hormone, called Thyrotropin Releasing Hormone (TRH). This hormone signals the pituitary to make TSH. When TSH levels are made artificially low by taking thyroid hormone replacement, it means that there may well be a correspondingly low TRH level. Among other things, TRH activates the Vagus Nerve. This is the longest nerve in the body. It is part of the autonomic nervous system, called the parasympathetic nervous system. In conjunction with its counterpart, the sympathetic nervous system, it influences and regulates essentially all internal organs, so it is rather important that these two parts be in balance. In addition, the vagus nerve is critical for the neuro-immune and brain-gut axis, through communications between the brain and gastrointestinal tract.
Low TRH equals low vagus nerve output. All the issues this may cause are beyond the scope of this blog. Four recent research papers will make it clear how critical normal vagus nerve activity is. The first one discusses that there is a dual anti-inflammatory nature of vagus nerve activity, either through the hypothalamic-pituitary axis or by inhibiting the production of a highly inflammatory chemical called Tumor Necrosis Factor-alpha (TNF-a) by white blood cells called macrophages in the spleen and peripheral tissues. Conditions such as Irritable Bowel Disease, that involve TNF-a could potentially be made worse with low vagus nerve function.
The second paper talks about the fact that normal vagus activity acting on the liver through several mechanisms, modulates insulin and blood sugar regulation and the production of inflammatory chemicals. Decreased vagal output may contribute to chronic liver inflammation.
Several recently published articles show the correlation between low vagus nerve output and depression. One discusses that increasing vagal output through a technique called vagal transcutaneous nerve stimulation significantly improves depression, while at the same time reduces production of pro-inflammatory chemicals, called cytokines.
Since the vagus nerve also supplies most of the digestive system, proper function plays a role in output of stomach acid, digestive enzymes, digestive hormones (serotonin, histamine, and ghrelin). Proper tone is critical for motility of the intestines. Low output can lead to constipation.
Can it possibly get worse? Yup. Impulses in the vagus nerve are produced by the neurotransmitter acetylcholine. The primary building block is choline, a semi-essential nutrient. If there isn’t enough choline, there may not be enough acetylcholine to provide optimal nerve transmission. There are several common gene mutations (called single nucleotide polymorphisms) that can reduce production of acetylcholine. In addition, a diet low in choline can make this worse.
Dr. David Brownstein, functional medicine thyroid expert and author of 13 books, tells us about the relationship between TSH and iodine. He relates that the total body amount of iodine when iodine stores are optimal, is about 1.5-2 grams. When the thyroid gland is fully saturated, there are about 50mg, so only 5% or so of total body iodine is in the thyroid. Iodine is found in every cell of the body. Many different glands, including the thyroid, concentrate iodine. In other words there is a lot more iodine inside the gland than outside, 20-50 times as much in fact. To accomplish this requires an active transport mechanism, which is called the sodium-iodine symporter. (NIS). This is the first step in the production of thyroid hormones.
TSH stimulates the production of sodium-iodine symporter protein. NO TSH, no NIS. You can see what happens when TSH is low; less TSH means less NIS, which in turn means less iodine getting into the thyroid, which means less thyroid hormones being produced, which now means that one must take more synthetic thyroid hormones to compensate. Now imagine that you are also deficient in iodine!
Finally, let’s turn everything your doctor knows about TSH that just ain’t so on its head. TSH stimulates the production of thyroid hormones by the thyroid. End of story, right? Sorry, that simplistic view is incorrect. In a 2017 paper, researches debunk this dogma. TSH was shown to have a direct effect (in other words not through thyroid hormone) on the skeleton, specifically the cells that build bone (osteoblasts) and tear it down (osteoclasts). TSH is built of two parts, called subunit A and B. It appears that subunit B can be produced by certain bone marrow cells and have a direct effect on the bone. Low TSH levels from the thyroid can also contribute directly to osteoporosis. TSH therefore has a protective effect on preserving bone density, and low TSH can contribute to osteoporosis
Hopefully these three blogs on TSH have shown you that evaluating and treating thyroid conditions is much more complicated than it appears, and much more involved than simply measuring TSH levels
About the Author: Dr. Douglas L. Weed
Dr. Weed practices Functional Nutrition, Chiropractic care, and offers weight loss solutions in Napa, CA at Heun Chiropractic, Inc. He has a doctorate in Chiropractic care and he has received certifications in physical rehabilitation and as a Qualified Medical Examiner. With a post-graduate certification in Functional Medicine, focusing on functional endocrinology, digestive disorders and Peripheral Neuropathy, he is committed to lifelong education and helping patience transform their health.