Thyrotoxicosis vs. Low TSH


Our medical system has invested so much in the TSH test that we’ve given it authority to override medical discernment about thyrotoxicosis.

The oft-repeated mantras that “TSH is the most sensitive and specific test” and “the only necessary test” have blinded many doctors to the diverse influences that can suppress or inflate TSH secretion.

Many doctors are reducing hypothyroid patients’ thyroid medication doses on the basis of a TSH number alone.

However, this TSH-centric view of thyrotoxicosis is inconsistent with the definition found in the most respected textbook in endocrinology.

This leading authority defines thyrotoxicosis based on high Free T3 (FT3) and Free T4 (FT4) levels and their effects on the body. The definition lacks any mention of TSH.

A low TSH simply can’t “cause” hyperthyroidism or thyrotoxicosis when FT3 and FT4 are not high enough to cause it.

Not only is a TSH-only definition of thyrotoxicosis unscientific, it is also harmful to patients on thyroid therapy.

Doctors’ kneejerk efforts to prevent low TSH when it comes at the cost of true thyroid hormone health is one of the most frequent problems patients complain about in thyroid patient support groups.

Doctors simply aren’t ordering the relevant thyroid tests or performing the physical examinations necessary to clearly discern what is going on. TSH alone cannot distinguish between hyperthyroidism, thyrotoxicosis and a falsely oversuppressed TSH during thyroid therapy.

This is causing unnecessary harm and suffering.

In this post and a subsequent series of posts, I try to clear things up.

  • I go back to the foundational definitions of thyrotoxicosis and advice on its diagnosis from one of the most authoritative textbooks in endocrinology today, from two editions.
  • I give an overview of situations during thyroid therapy in which low TSH is not an adequate judge of thyrotoxicosis.
  • In a series of several posts, I provide research findings about the various factors that can cause thyrotoxicosis and/or manipulate the TSH to behave abnormally in relation to thyroid hormones.

It’s so important to put a full set of lab test results, TSH, FT3 and FT4, in their proper place within the interpretive context of a patient’s clinical history and presentation.

Official definitions of thyrotoxicosis

The venerated bible of thyroid endocrinology, the massive, 1000-page textbook Werner and Ingbar’s The Thyroid, now in its tenth edition, explains very clearly that the pituitary suppression of TSH is not part of the definition of thyrotoxicosis. 

The core definition hasn’t fundamentally changed since the co-editors of the textbook, Braverman and Utiger, explained this fundamental distinction at the opening of Chapter 28, “Introduction to Thyrotoxicosis,” in the 8th edition, year 2000:

“We use the term thyrotoxicosis to mean the clinical syndrome of hypermetabolism that results when the serum concentrations of free thyroxine (T4), free triiodothyronine (T3), or both, are increased.

The term hyperthyroidism is used to mean sustained increases in thyroid hormone biosynthesis and secretion by the thyroid gland. Thus, the terms thyrotoxicosis and hyperthyroidism are not synonymous.”

Where is TSH in this definition? Nowhere.

Not only is a low TSH not the cause of thyrotoxicosis, it isn’t even a necessary or sufficient sign worthy of mention in the opening definition.

TSH comes in later, when stipulating a distinction between subclinical and overt.

We also learn that thyrotoxicosis also isn’t the same as hyperthyroidism, even though people often use these words interchangeably.

In the 10th and most recent edition, Braverman and Cooper only slightly revised the first sentence of this definition. They clearly thought it was worth repeating and refining:

“We use the term thyrotoxicosis to mean the clinical syndrome of hypermetabolism and hyperactivity that results when the serum concentrations of free thyroxine (T4), free triiodothyronine (T3), or both, are elevated.”

Notice that the health outcome is specified as “the clinical syndrome of hypermetabolism and hyperactivity,” two words that emphasize the physiological response.

The main cause of this syndrome is serum free T4 and/or T3, described either as relatively “increased” in quantity, or as “elevated,” which adds the idea that these hormone levels in blood are above a standard set for normal.

The chapter lists and alludes to situations in which variation in response to an abnormal “elevation” of hormones doesn’t necessarily result in the syndrome of hypermetabolism, such as receptor resistance to thyroid hormone and HCG-inflated T4 levels during pregnancy.

When it does come into the chapter, TSH is always placed alongside both thyroid hormone measurements as a set, and the low TSH is not the main emphasis.

According to this authority, lab tests are secondary to the physical or clinical examination necessary for making a correct diagnosis:

  • 1) whether hypermetabolism is actually occurring in the body, and
  • 2) its cause(s).

Lab tests are not sufficient data when deciding what action to take, if any.

The TSH in thyroid therapy

The major problem with TSH-only diagnosis is the assumption that TSH behaves the same way and means the same thing in two very different situations:

1) before thyroid therapy begins and

2) during thyroid therapy.

Before therapy begins, the HPT axis is unbroken and functioning normally and without external interference, unless the hypothalamus and pituitary are compromised (central hypothyroidism). Therefore, outside of thyroid therapy, TSH is more likely to be an accurate reflection of thyroid hormone status.

But in the context of thyroid therapy, very paradoxical configurations of TSH, FT3 and FT4 are common, even without central hypothyroidism. Major distortions of the HPT axis are possible.

In populations whose TSH is low during levothyroxine (LT4) therapy, some people will be poor converters of T4 into T3. In their bloodstream, only the Free T4 is singlehandedly oppressing TSH, while Free T3 may be low-normal or even below reference range.

New clinical research in thyroid therapy has proven that “Dosing and disease” can work together to unnaturally manipulate the TSH. In therapy, the main sign of the broken HPT axis is that TSH now has an abnormal relationship to T3, the most powerful and essential thyroid hormone. There’s a clear TSH-T3 disjoint that can become more and more extreme as thyroid tissue is killed or removed and more thyroid hormone must be dosed.

Most frequently, full thyroid-replacement doses in LT4 monotherapy can expose underlying handicaps in T4-T3 conversion, causing a low T3 together with an elevated T4, which can singlehandedly suppresses TSH despite the need for more T3 hormone. This is the TSH-T3 disjoint.

In many cases the doctor’s decision to reduce thyroid hormone dosage is quite contraindicated, as when the low TSH coexists with one or both thyroid hormone measurements below reference or in the lower half of reference range.

It is grossly anti-biological to make the muffled voice of a lower TSH silence the screams of low-normal or low T3 levels, especially if hypothyroid symptoms are present.

In some people with Graves’ disease after a total thyroidectomy, TSH may remain suppressed for months or years, even when thyroid hormones are normal or low because the TSH receptor-stimulating antibodies (TSAb) are still active.

This happens due to antibody interference. When TSH-receptor thyroid antibodies enter TSH receptors in the pituitary, they make the pituitary think it’s secreting too much TSH.

The pituitary’s ultrashort feedback loop that regulates TSH secretion has been known since the 1990s and is even so famous in science as to be named after its discoverers: the “Brokken-Wiersinga-Prummel Loop” (discussed by Dietrich et al, 2012).

But do clinicians learn about this and how thyroid antibodies interfere? Unfortunately, not many of them are aware of it.

In populations whose TSH is low during T3-inclusive therapies, the Free T4 may be mid-range or lower, mildly below reference. In LT3 monotherapy without a thyroid function, FT4 may even be unmeasurable. An isolated high FT3 may suppress TSH due to the hypothalamus and pituitary’s unique sensitivity, but systemic thyrotoxicosis is not always the result.

People with “untreated” and “treated” thyroid disease are two very different populations. The TSH can be misleading if interpreted using the “normo-thyroid” population’s reference range boundaries.

How does this occur at the cellular level?

In thyroid therapy, the HPT axis is no longer a “closed feedback loop” working in both directions, both feed-forward to stimulate the thyroid, and biologically-generated thyroid hormone feedback to adjust TSH.

Instead, in thyroid disease and therapy, the HPT axis is a broken, unidirectional “open loop” in which thyroid hormone dosing interferes with natural T4:T3 ratios and levels and even circadian rhythms.

The negative feedback loop on TSH secretion is subject to strong interferences from other biochemical signals besides T4 and T3. TSH can be falsely oversuppressed by:

Therefore, decreasing the thyroid hormone dose just to increase the TSH can cause or worsen a FT3 deficiency and deepen a patient’s tissue hypothyroidism.


Some are yet to be published and will be linked when the links are published.


See References for Thyrotoxicosis vs. Low TSH series

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