We should all know that thyrotoxicosis in bone, caused by too much T3 binding to receptors in cells, leads to osteoporosis. (Bassett et al, 2007; Gogakos et al, 2010)
Hypothyroidism in bone, characterized by low T3 in bone, is not good for bone, either. (Bassett et al, 2008)
Hypothyroidism results in a different bone disorder you rarely hear of: osteoSCLERosis. (Williams, 2013; Bhatnagar et al, 2017).
After the prefix “osteo” meaning bone, the word “sclerosis” means abnormal hardening.
How many studies and clinical cautions focus on this problem of local T3 deficiency in bone leading to sclerosis? Few.
It’s such a rare word that even my spell-checker is highlighting “osteoclerosis” as a spelling error.
HOW IT WORKS
In hypothyroidism, T3 deficiency exists in bone cells.
Due to lack of T3 binding to receptors in cells, bone turnover slows down, and bone mineral density is increased. It may increase so much that it leads to osteosclerosis.
Osteosclerosis contributes to bone stiffness.
Bone quality is also more likely to be poor due to low calcium and vitamin D status, which is common in hypothyroidism.
These factors together increase risk of fracture in stiff, dense bones. (Bhatnagar et al, 2017).
In fact, “hypothyroidism is associated with a two- to three-fold increased risk of fracture, whilst thyrotoxicosis is an established cause of osteoporosis and fragility fracture.” (Williams, 2013).
This similar health outcome (fracture) in both high and low thyroid hormone can be confusing to people who want to see the two thyroid hormone disorders as complete opposites in every way.
In an effort to explain the higher fracture rates in people with hypothyroidism who don’t have osteoPORosis, some researchers have suggested that fracture rates are higher in some hypothyroid patients because they have problems with balance while walking and are more likely to fall (which may also be true).
However, fracture is not the only sign, symptom, or health outcome that occurs at both ends of the hypo-hyper spectrum. The list of symptoms found in both hyper- and hypothyroidism includes heart disease, high blood pressure, hair loss, fatigue, and chronic anxiety. This often confuses doctors and patients.
The symptoms and signs and health outcomes of hypothyroidism or thyrotoxicosis will depend on how the individual patient’s body is attempting to compensate for their unbalanced thyroid hormone levels. Thyroid patient communities know symptoms will often present at the weakest link in the chain, the most vulnerable organs and tissues.
In hypothyroid patients, which hormone has the most direct and profound effect on osteosclerosis, poor bone quality, and fracture? High TSH, low T4, or low T3?
A high TSH may indeed worsen hypothyroidism in bone, according to molecular endocrinologists who have carefully studied the action of TSH, T4, and T3 in bone.
However, the hormone that sticks farthest out of reference range is not necessarily the one that causes the biggest problem.
The experts believe a more likely candidate is low T3 in bone.
In studies of mice who are bred with a defect in the dominant thyroid hormone receptor found in bone, THRA, they can look perfectly fine in their thyroid hormones and TSH levels in blood, but they can develop hypothyroid, osteosclerotic bones. (Williams, 2013)
In addition a flaw in Deiodinase type 2, the enzyme responsible for converting T4 to T3 within bone, is a culprit. “Studies of mice with deletion of the Dio2 gene further demonstrate a critical requirement for T3 in osteoblasts . Dio2 knockout mice have increased bone mineralization density and brittle bones due to impaired osteoblast activity.” (Williams, 2013)
Williams explains that all this research proves “impaired T3 action in skeletal cells” is the key factor that leads to osteosclerosis, not the elevated TSH found in untreated hypothyroidism.
The same principle is often found by researchers who study thyroid hormones in other organs and tissues.
HYPOTHYROIDISM IS HYPO-T3-ISM
T3-toxicosis is an official word in endocrinology. I’m not sure why hypo-T3-ism should not be a word for the opposite condition of isolated low(er) T3.
From the perspective of any given organ, including bone, the state of “hypothyroidism” is neither caused nor defined by a high TSH, but primarily by T3 insufficiency.
In addition, low T3 within tissues correlates with low(er) T3 in blood, as it does in overt hypothyroidism.
Too many people are looking for a high TSH to co-present with hypothyroidism because that’s how our medical culture has defined it, as something sticking out of a reference range. It’s not how our body defines it.
It’s also not our body’s fault that the Free T3 reference range cutoff is so low that it hides genuine hypoT3ism within the reference range so that it looks normal.
This is why I resort to saying “low(er) T3,” because of the deceptively low Free T3 reference cutoff. (The problems are also caused by the challenges with testing lower concentrations of this very precious and essential hormone using diverse assay kits nobody has bothered to standardize.)
As mentioned above, hypothyroidism often presents with low vitamin D. In a research study of hypothyroid patients, Low Vitamin D was strongly correlated with lower T3 levels in blood, even while T3 was within reference range. It was more strongly associated with T3 than with TSH, and not at all with T4 levels. (Mackawy et al, 2013)
IGNORING LOW(ER) T3
No wonder this process of osteosclerosis and its cause, low(er) T3 in bones, which co-presents with low(er) T3 in blood in overt hypothyroidism, seems to be unknown to many researchers and physicians.
A 2016 case study of a middle aged woman with lupus found that she had osteosclerosis. Although lupus is an autoimmune disorder and may co-present with autoimmune hypothyroidism, nobody thought to measure her thyroid hormone levels or look into history of hypothyroid symptoms. Every other biomarker under the sun was mentioned. Over many tests throughout the years, her ferritin and serum iron were rather low, a finding often occuring in hypothyroidism. Her vitamin D levels were rather low. Serum calcium varied within reference. There was no mention of T3 or even of the word “thyroid.” (Guañabens et al, 2016)
OSTEOCLEROSIS IN THYROID THERAPY?
The blindness to osteoclerosis has practical implications for treated thyroid patients who suffer chronic symptoms of hypothyroidism while their TSH is normalized.
Who has studied treated thyroid patients’ chronic low T3 levels in relation to their bone mineral density to look for osteoSCLERosis?
No one, that I can find.
Everyone is assuming that because their TSH is normalized, they are no longer hypothyroid.
Given the wide diversity in patients’ response to T4 monotherapy, a significant percentage of patients remain chronically hypothyroid in T3 levels in their blood. (Midgley et al, 2015; Gullo et al, 2011)
Many of these patients are being maintained at a Free T3 level below the mean (average, not reference range) found in healthy people at the same TSH. They live in a T3 deficit, from the perspective of population statistics.
If they are relatively T3-impoverished in blood, what about their tissues?
In a state of thyrotoxicosis, hypermetabolism in tissues often correlates with elevated T3.
Likewise, in a state of hypothyroidism, symptoms in tissues often correlate with a Free T3 level below the average found in the healthy population, even if it’s not (yet) below reference range.
Many patients remain symptomatically hypothyroid even during TSH-normalized thyroid therapy while Free T3 is low within reference range, and this reduces their quality of life for the rest of their lives.
How long does it take for even mild hypothyroidism during therapy to add up its effects over the years?
In some patients, does chronic Low(er) T3 in blood and/or chronic hypothyroid symptoms result in syndromes like osteosclerosis and fragile bones?
Do bones symptomatically “ache” when they are low in T3?
Does mild hypothyroidism lead to risk of fracture in one’s 80s and 90s?
Can supplementing Vitamin D and calcium compensate for the bone stiffness of osteosclerosis?
Can increasing the patients’ Free T3 supply strengthen brittle, fragile bones?
END OUR EXCLUSION
Thyroid patients should rise up against their unethical exclusion from research.
Why is nobody studying the long term health effects of our chronic below-average Free T3 while on therapy, such as effects on our bones and joints?
There are millions of us being treated for hypothyroidism with T4 medication, which is well known to raises our T4 and lower our T3 per unit of TSH. Some patients have much lower T3 levels than others.
Those who wish to defend T4 monotherapy at all costs will claim that our significantly reduced T3:T4 ratio is unimportant because it’s not sticking out of reference range and because not enough research has shown there’s anything wrong with it.
They clearly aren’t reading studies on low Free T3:T4 ratios and lower T3 correlations with diseases. They are obviously not in a hurry to do the missing research to show anything is wrong with it.
We treated thyroid patients ought to be front and center in studies that focus on isolated low(er) T3 and health outcomes, since so many of us suffer from a low or low-in-range T3 despite normalized TSH and high-normal T4.
We are perfect test subjects for such studies.
You don’t need to recruit genetically altered mice. Hello! Here we are!
Our invisibility to research exists partly because policies often forbid measuring Free T3 during hypothyroid therapy. Most doctors and patients are left in the dark about Free T3 levels in thyroid patients who suffer and age. Only a few researchers know how often it happens and what it means to patients’ lives. Well-informed thyroid patient communities know what “suboptimal T3” means to our lives.
Under the normalized TSH potentially hides a multitude of Low(er) T3 maladies.
It’s time to look in the right place for these maladies, understand them, and stop them.
- Tania S. Smith
Bassett, J. H. D., O’Shea, P. J., Sriskantharajah, S., Rabier, B., Boyde, A., Howell, P. G. T., … Williams, G. R. (2007). Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism. Molecular Endocrinology (Baltimore, Md.), 21(5), 1095–1107. https://doi.org/10.1210/me.2007-0033
Bassett, J. H. D., Williams, A. J., Murphy, E., Boyde, A., Howell, P. G. T., Rowan Swinhoe, … Graham R. Williams. (2008). A Lack of Thyroid Hormones Rather than Excess Thyrotropin Causes Abnormal Skeletal Development in Hypothyroidism. Molecular Endocrinology, 22(2), 501–512. https://doi.org/10.1210/me.2007-0221
Bhatnagar, S., Srivastva, R. K., Jahan, S., & Ranjan, R. (2017). Multiple Effects of Hypothyroidism on Bone Mineral Density and Its Association with Vitamin D, Serum Calcium: A Cross-sectional Study. International Journal of Scientific Study, 5(6), 120–124.
Gogakos, A. I., Duncan Bassett, J. H., & Williams, G. R. (2010). Thyroid and bone. Archives of Biochemistry and Biophysics, 503(1), 129–136. https://doi.org/10.1016/j.abb.2010.06.021
Guañabens, N., Mumm, S., Gifre, L., Gaspà, S. R., Demertzis, J. L., Stolina, M., … Whyte, M. P. (2016). Idiopathic Acquired Osteosclerosis In A Middle-aged Woman With Systemic Lupus Erythematosus. Journal of Bone and Mineral Research : The Official Journal of the American Society for Bone and Mineral Research, 31(9), 1774–1782. https://doi.org/10.1002/jbmr.2842
Gullo, D., Latina, A., Frasca, F., Squatrito, S., Belfiore, A., & Vigneri, R. (2017). Seasonal variations in TSH serum levels in athyreotic patients under L-thyroxine replacement monotherapy. Clinical Endocrinology, 87(2), 207–215. https://doi.org/10.1111/cen.13351
Mackawy, A. M. H., Al-ayed, B. M., & Al-rashidi, B. M. (2013). Vitamin D Deficiency and Its Association with Thyroid Disease. International Journal of Health Sciences, 7(3), 267–275.
Midgley, J. E. M., Larisch, R., Dietrich, J. W., & Hoermann, R. (2015). Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency. Endocrine Connections, 4(4), 196–205. https://doi.org/10.1530/EC-15-0056
Williams, G. R. (2013). Thyroid Hormone Actions in Cartilage and Bone. European Thyroid Journal, 2(1), 3–13. https://doi.org/10.1159/000345548