Fear of Low TSH causing osteoporosis

T3 levels and bone

Image based on Figure 4 in this source:

Dear Doctors,

You may experience this scenario with some of your thyroid patients.

Your patient’s TSH is near the bottom of reference range, but they are still experiencing symptoms of hypothyroidism.

Do you increase the dose? How can you do that if their TSH is borderline low?

You’re genuinely afraid for your patient’s health.

What about osteoporosis, you ask? Isn’t that associated with low TSH? (Oh, and heart disease too, but that’s a topic for another post: “Low T3 effects on the cardiovascular system.”)

Doctors, we plead with you. Use the critical thinking skills we trust that you learned during medical school. Question this “statistical association” between low TSH and disease risks.

Diseases may be “statistically associated” with TSH levels. That does not mean they are “biologically caused” by TSH levels alone, independent of thyroid hormone levels.

Ask this: What functional mechanism is underneath this TSH association?

Scientific studies have already proven that TSH can’t directly “cause” the damage associated with either extreme of hyperthyroidism or hypothyroidism.

As of 2018, there is still no proof that low TSH hormones play a role in causing osteoporosis.

Bassett and Williams’s 2018 textbook chapter on “Thyroid hormone in bone and joint disorders” states very clearly that “Studies have been conflicting regarding the relative roles of thyroid hormone and TSH. Importantly, this issue cannot be resolved when the HPT-axis remains intact and the reciprocal relationship between thyroid hormones and TSH is maintained” (p. 556).

In other words, the studies that focus only on patients UNtreated with thyroid hormone with healthy thyroid glands (people whose HPT-axis remains intact) can’t distinguish between the causal role of high thyroid hormones versus low TSH. When the reciprocal relationship between TSH and thyroid hormones is intact, and there is both positive regulation and negative feedback between them, you can’t say which hormone plays more of a causal role than the other.

For all we know, low TSH could simply be a factor often associated with the conditions that cause osteoporosis. Correlation/ association is not causation.

So why is there an association with low TSH and health risk? It has already been explained in the scientific literature.

It’s not about the TSH level. It’s about T4 & T3 in blood, and primarily T3 levels in tissues.

Do you know why there are TSH receptors located beyond the thyroid gland, and why they are located on bone cells?

It is not because the bone always cells stay healthier with stimulation from TSH and they always fall apart without TSH. Not at all.

It’s all about TSH’s mild role in helping T4 become T3 in peripheral tissues.

TSH is not only a driver of T3 secretion (from a healthy thyroid gland) but also an upregulator of peripheral T4-T3 conversion (via Deiodinase Type 2). (Hoermann et al, 2015).

In bone cells, TSH functions primarily by means of the mild influence it has over upregulating thyroid hormone conversion.

However, TSH is not the major driver. “The data” on mice with thyroid hormone receptor variations indicate that “the effects of disrupted or increased T3 action in bone predominate over skeletal responses to TSH” (Bassett and Williams, p. 532).

  1. NORMAL: When there is a healthy amount of T4 and T3 in bloodstream, some T4 enters cells before it is converted into T3, and some T3 enters cells without any further need of conversion. A healthy level of TSH stimulates further T4-T3 conversion within cells so that they get just the perfect amount of T3 they need. This promotes healthy cells and tissues.
  2. HYPO: If the deficit of thyroid hormone in bloodstream is too extreme, high TSH can’t make more thyroid hormone appear out of nowhere. Also, if T4 is abundant in blood but both T3 and TSH are low, then the insufficient TSH cannot stimulate enough T4-T3 hormone conversion to make up for the T3 deficit in bloodstream. Either way, whether a patient has high TSH or low TSH, cells and tissues will starve slowly, but can still suffer severe, long-term damage — from local Low-T3 hypothyroidism. Although bone does not become osteoporitic, bone turnover is low and mineralization increases. Bones become brittle when local T4-T3 conversion is deficient. In children, this also hinders bone development and they can become short of stature.
  3. HYPER: When there’s way too much T3 or T4 in blood, the TSH will go low in response.  If there is an excess of T3 in bloodstream, the absence of TSH is absolutely powerless to prevent that excess T3 from entering cells. TSH is not in charge of transport of T4 and T3 into cells, as far as we know so far. Excess T3 in bone cell receptors will overstimulate cellular activity. If excess T3 keeps coming in, it will cause tissues to suffer, and fairly quickly, from loss of bone mineral density.

Read a summary of the studies that prove this: “Rationale: Low TSH vs. true hyperthyroidism.”

Clinical Study by Heemstra, et al

Here’s an example of one good clinical study of the effect of TSH versus T4 and T3 on bone health biomarkers in treated thyroid patients.

Researchers studied 22 patients without thyroid glands 5 years after thyroidectomy from differentiated thyroid cancer (DTC).

Baseline: They first measured everyone’s baseline biomarkers. On these patients’ prescribed TSH-suppressive L-T4 therapy, their pituitary and thyroid hormone levels were, on average:

  • low TSH 0.06 – 0.8 Mu/L (ref 0.3-4.8)
  • high Free T4 – 23.4 – 24.8  pmol/L (ref 10-24)
  • low Free T3 – 1.3- 1.8 pmol/L (ref could be ~2.0-6.0 ?? — oddly, range not mentioned)

Intervention, Group 1: Then, they took away 11 patients’ L-T4 monotherapy for 4 weeks and did careful measurements. Averages:

  • High TSH – 142.4
  • Low FT4 – 1.4
  • Very low FT3 – 0.3. Ouch!

Intervention, Group 2: They kept the other 11 patients on stable L-T4 therapy but injected them with extra TSH molecules — recombinant human TSH (rhTSH).  Averages, Day 1:

  • High TSH 143.4
  • High FT4 24.0
  • Low FT3 1.8.  Still, ouch.

By Day 3, group 2 had the same thyroid hormone levels, but TSH was only moderately high at 19.3, since the injected rhTSH molecules were leaving bloodstream.

What did the researchers find from the markers of bone metabolism in these groups?

“Our findings suggest that acute increases in TSH in the presence of stable thyroid hormone levels obtained by rhTSH administration do not significantly affect skeletal metabolism.

The data from our model suggest that hypothyroidism results in decreased bone turnover rather by decreased plasma thyroid hormone concentrations than by increased TSH concentrations, because rhTSH did not impact on bone turnover in DTC patients.”

In other words, hypothyroidism in bone is defined as insufficient Free T3 in plasma.

Even a superduper high TSH won’t help you enough if you have high Free T4 but low Free T3.

Unfortunately, these poor patients’ T3 levels were kept extremely low at an average of 1.8 pmol/L – 0.3 pmol/L, whether or not they were on L-T4 therapy, so they were always hypo-T3. What was the long term effect of their low T3, I wonder? Someone really needs to do a long-term follow up study on low T3 in TSH-suppressed patients.

How to read research studies on TSH risk

If you read a study on TSH and osteoporosis (or any health risk), ask these important questions as you read.

  1. Did they measure patients’ Free T3 levels? How can we know for sure if “Low TSH” played a role independent of both T4 and T3 hormones if a population study did not measure Free T3?
  2. How long-term was the study and did they measure Free T3 at many points?  Do we know whether the patients at risk suffered from a continually low or high T3 over years? In the case of risk for osteoporosis, low T3 may have immediate or short term effects on bone biomarkers, but it takes a lot more time to cause endpoints like bone fractures and overall low bone density. High T3 takes less time to achieve those endpoints because it speeds up bone turnover.
  3. Did they divide patients into cohorts or “tertiles” by their Free T3 levels? If they just took all the T3 values and averaged them together, they will be blinded to the association with T3, because both low T3 and high T3 cause the same risk. If you average the data, they will mathematically cancel each other out. There won’t be the “linear” association that most researchers look for, because that’s not how T3 works in biology. Only when you divide patients into groups by high, normal and low T3, will you be able to see how T3 influences the same risk factors at both ends of the spectrum.
  4. Did they divide patients into categories or cohorts by their TSH levels?  If they did not also divide them into cohorts by Free T3, they are simply barking up the wrong tree. If studies try to put patients into categories like “subclinical hypothyroidism” or “subclinical hyperthyroidism,” realize that these categories only exist based on TSH. Unfortunately, TSH response can be contradictory within these “gray zones” and that is why they are controversial zones (a person can have low, or normal, or high T3, and the TSH alone does not tell you what it’s responding to). These researchers are likely looking for the TSH associations they want to see. They will not likely be gathering the relevant data or looking for the patterns in data that might get them to rethink their TSH-based hypotheses.
  5. Were the populations studied NOT on thyroid hormone therapy? Read the methods section and see which populations were excluded. If thyroid patients were excluded, their study’s results simply do not apply to that population. In the UNtreated state, a low TSH normally exists in the presence of high T4 and/or high T3. But this is not the case in thyroid therapy. The TSH-T3 relationship works very differently in people who are taking thyroid hormones. (see “Rationale: The T3:T4 ratio“).
  6. Did the study focus on thyroid patients taking high doses of L-T4 thyroid hormone that could suppress TSH without elevating T3? Did it take into account the fact that TSH-suppressive therapy can actually push some patients’ T3 below range while T4 alone is high in reference?  (see TSH untrustworthy in thyroid therapy)
  7. Did the study eliminate those suffering from health conditions such as fasting, depression, inflammation, or chronic illness such as chronic fatigue syndrome (CFS), which can cause low (not high) T3 levels simultaneously with a low or moderately low TSH? (See Rationale: Low T3 Syndrome, part 1)
  8. Did they explain how TSH could have any direct effect without influencing T4-T3 conversion within organs and cells? This is the clincher. Read their “Discussion” section. If all they do is cite other TSH-association studies, you are in an echo-chamber of association studies. They are not asking the essential question about how TSH functions to bring about health risk.

Ultimately, if you want to understand the true cause-effect relationship between TSH, thyroid hormone levels, and diseases, read some molecular biology research.

Only researchers who have observed how TSH, T4 and T3 work within cells (i.e. when studying rats or mice) can theorize or come close to proving true causality. Only they are charged with the duty of actually explaining the functional mechanisms by which these hormones affect mammals at the cellular level. Only those studies can help you understand whether low TSH, low T4 or low T3 is more likely to “cause” harm independently, or if two or more factors need to be combined in order to have a harmful effect.

Sadly, not enough clinical and epidemiological research has been done on T3 levels and health risk. The vast majority of research has not been studying the right hormone, but the convenient hormone. Not many studies have used the research methods that can reveal T3’s direct influence.  But molecular biology already tells us a lot–T3 is the thyroid hormone that has the biggest influence.

Implications for thyroid therapy

Doctors and patients can do two things:

  1. Measure Free T3 and Free T4, not just TSH, whenever a patient is symptomatic on therapy.  Be aware that symptoms are usually connected to T3 because it’s the active hormone.
  2. If L-T4 monotherapy is maintaining them in a state of lower TSH, higher T4 and lower T3, realize that their bones and heart are likely at risk from their lower T3 most of all. Change their therapy modality.

The most important hormone level to optimize is our active hormone Free T3, not the TSH hormone.

TSH’s main role (if it is no longer needed to stimulate a healthy thyroid gland to produce hormones) is to mildly boost peripheral T4-T3 conversion when there is a slight T3 deficiency in blood.

At any level of TSH, a high-normal T4 can’t help a patient who is suboptimal in Free T3.

Given what we know from T3-based research, a low TSH cannot, on its own, damage a patient who has sufficient, not excessive, T3.

Consider putting the Lower-T3 patient on some T3 hormone to raise the T3 level while reducing their T4 intake. You can do this either with synthetic L-T3/T4 combination therapy or animal-derived desiccated thyroid (DTE / NDT) combination therapy. Combination therapy will permit their T3 to reach optimal levels without having T4 hit the “ceiling” first. A patient taking sufficent T3 will be less dependent on T4-T3 conversion aided by TSH.

Read more about this therapy modality in “Rationale: L-T3-T4 combination therapies“.

In conclusion

Too often, doctors fear low TSH and T3-hyperthyroidism (or overdose) far more than high TSH or T3-hypothyroidism (or underdose).

This may be because the effects of extreme hyperthyroidism are more swift and dramatic: thyrotoxicosis, thyroid storm, cardiac arrest, death.

But we believe that a significant portion of treated thyroid patients suffer from chronic hypothyroidism from imbalanced T3:T4 ratios and/or suboptimal T3.

Untreated low T3 hypothyroidism is a long, slow form of torture and medical harm. It goes undetected and unrecognized because statistical reference ranges will often tell us we’re “normal.” It ruins patients’ careers, families, communities by sapping our energy and life from us. And it very likely causes long term harms to health that are yet to be revealed in clinical studies because of their flawed assumptions and methodologies.

See our further discussion of this research:  Rationale: Low TSH vs. true hyperthyroidism

See other blog posts on the Low TSH topic, such as:



9 thoughts on “Fear of Low TSH causing osteoporosis

  1. This all makes sense However, one thing that nobody ever talks about is the fact that there is an increased risk of osteoporosis and heart issues in people with a low TSH and normal T4/T3 levels. I always thought the issue was with high levels of actual thyroid hormones, so am confused that this risk appears with a suppressed TSH even in the case of normal T4 and T3 as happens in subclinical hyperthyroidism. Why are these risks present with subclinical hyperthyroidism?

    1. Thanks for your question, Lynn.

      These questions haven’t yet been answered. Not every “normal T3 and T4 + low TSH” configuration in thyroid therapy has been investigated yet in research.
      Therefore we can’t conclude that risks are caused by all forms of subclinical hyper.

      When both T4 and T3 hormone are in the upper quartile or quintile of reference range, hormones are capable of not only lowering TSH but also harming bone metabolism. This is what one may call “normal subclinical hyper.”

      Not all cases of subclinical hyper are “normal,” with both thyroid hormones close to the tipping point.

      Consider two thyroid therapy situations where only one of the thyroid hormones in the upper-normal reference range is capable of suppressing TSH while the rest of the body is not necessarily in a hyperthyroid state because the other hormone is low-normal (or low):

      1) people treated with Levothyroxine alone who have extremely low FT3:FT4 ratios.
      In this population, the higher T4 alone can lower or suppress TSH while the very low-normal level of T3 active hormone may leave many of their organs potentially in a hypothyroid state. Yet the term “subclinical hyper” is applied to them presumptively. This population has a strongly unnatural TSH-T3 disjoint. — Where are the osteoporosis risk studies that focus on this population?

      2) people being treated on T3 monotherapy or T3-heavy synthetic T3-T4 combinations, or desiccated thyroid, with a high T3:T4 ratio.
      These are people whose T3 dosing side-effect is pituitary TSH lowering or suppression. The dosing effect can do so even when T4 hormone is low-normal, and while the daily average T3 level is in normal range. This population has a TSH-T4 disjoint — Where are the osteoporosis studies on this population?

      Next, if lack of TSH is independently a cause of osteoporosis in subclinical hyper, there should have been studies conducted on people with various degrees of central hypothyroidism whose T4 and T3 are mid-range and no higher. Their TSH is lacking for reasons other than excess thyroid hormone. Where are the studies in central hypo and osteoporosis?

  2. I have hashimoto’s and osteoporosis. My endocrinologist says my TSH should be between 2 and 4 due to the osteoporosis. It is currently at a 1.9.
    Please let me know if you have any information regarding this. Thank you so very much!!

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