Table 17.1 in Braverman & Cooper’s 2013 chapter in Werner & Ingbar’s The Thyroid textbook, 10th edition, lists many causes of thyrotoxicosis.
The only time the TSH _hormone_ is listed as a cause of thyrotoxicosis is in the case of “Inappropriate TSH hypersecretion.”
If thyrotoxicosis can occur when TSH is inappropriately _high_ or non-suppressed in relation to elevated circulating thyroid hormone levels, then you can’t define thyrotoxicosis by a low TSH level alone.
A low TSH can’t even be part of the definition of thyrotoxicosis.
A TSH test in general, however, is an essential part of the diagnosis of inappropriate TSH hypersecretion as a cause of thyrotoxicosis.
TSH-SECRETING PITUITARY TUMOR
One cause of TSH hypersecretion listed by Braverman & Cooper is a “TSH secreting pituitary tumor,” which is rare.
The extra TSH secretion may drive thyroid secretion higher than the metabolic set point of the individual, and this may be quite confusing while all three levels are within reference range, or while TSH is high and T4 and T3 levels are rising within reference.
Analysis with the SPINA-Thyr program can assess whether TSH is significantly higher given the T4 level normally required to suppress TSH even while all three values are in reference.
A “TSH-oma” can co-present with other causes of thyrotoxicosis and may be completely overlooked if a doctor does not perform careful diagnosis.
RESISTANCE TO THYROID HORMONE (RTH)
Another cause of inappropriately high TSH hypersecretion is “Pituitary resistance to thyroid hormone,” pituitary-RTH.
This condition is currently considered rare, but that is because it is rarely diagnosed. Doctors are unaware of its signs and characteristic laboratory test patterns, so it can be missed.
In people with this condition, the thyroid receptors in the pituitary gland and/or hypothalamus are genetically flawed. One or the other thyroid hormone is elevated but TSH won’t fall low in response. These receptors need more thyroid hormone than normal to make their tissues euthyroid. (Refetoff et al, 2014; Dumitrescu & Refetoff, 2013)
This syndrome can be found in people with any and all types of thyroid disease — Hashimoto’s, thyroid cancer, thyroiditis, multinodular goiter, you name it. It’s genetic. This is usually a polymorphism in the THRB gene.
In a RTH patient with hypothyroidism who is taking thyroid hormones, their TSH will also fail to normalize or suppress despite higher levels of thyroid hormone in blood.
RTH EFFECTS: NOT NECESSARILY THYROTOXICOSIS
When thyroid hormone resistance is “generalized,” other tissues in the human body will also require higher than normal levels of thyroid hormone to maintain health.
In the case of generalized RTH, a person is NOT necessarily thyrotoxic even when their thyroid hormones are elevated above normal. It would be harmful to reduce the level of circulating thyroid hormones if the person’s body needs them to be high.
In these patients, you can’t assume that their TSH is an indication of their entire body having enough thyroid hormone. In RTH, each organ can be affected to a different degree based on the type of thyroid hormone receptors it expresses.
If the THRB receptors have resistance but THRA do not, the heart and other THRA-expressing tissues can be overdosed while other organs will be fine. You have to judge more by symptoms and signs and the degree to which the hormones are beyond reference.
Even a pregnant woman with RTH and thyroid hormones elevated 20% above the reference range may not endanger her fetus by hormone levels this high. (Wu et al, 2018)
Because a person may have RTH in conjunction with other thyroid disorders and in the presence of thyroid medications, making a correct diagnosis complex.
It may be possible to discover a compromise, a range of T4 and T3 hormone that is able to meet the needs of tissues with no THRA resistance and also tissues with THRB receptor resistance.
If it is not, I recommend consulting the research literature on RTH therapy, which is discussing alternative thyroid hormone metabolites like TRIAC that operate differently on the different types of thyroid hormone receptors.
Nobody can detect a TSH-oma or RTH disorders by testing TSH alone. However, you can detect them by measuring the person’s Free T3 and Free T4 levels together with the TSH.
All three hormones in relationship can give clear signs that there is a contradictory TSH result.
Various degrees of Resistance to Thyroid Hormone exist. Some are selective to the pituitary and others are generalized, and the difference between the two can be detected by symptoms and signs, not just by unexpectedly high or normal TSH.
If a doctor wrongly expects TSH to fall low or become suppressed in all cases of thyrotoxicosis, then TSH-inflating factors can mask the diagnosis and lead to incorrect therapy decisions.
We learn from RTH research that some people simply need more thyroid hormone than is statistically “normal” to achieve euthyroid status.