How TSH ultrashort feedback works, and antibody interference

Chatzitomaris-Ultrashort feedback loop

This post takes a closer look at the “ultrashort feedback loop,” the biological mechanism by which the TSHR stimulating antibody (TSAb) can oversuppress TSH in any autoimmune hypothyroid patient.


This feedback loop was first discovered in 1984 in rabbits (Kakita et al, 1984, 1986) and demonstrated conclusively in humans in 2004 by Johannes Dietrich and colleagues. It is still omitted from simplistic images showing the HPT axis (hypothalamus-pituitary-thyroid axis), but it does appear on complete visual models (Chatzitomaris et al, 2017).

The TSH ultrashort feedback loop is important to a normal HPT axis.

The pituitary gland uses this ultrashort feedback loop to adjust its TSH secretion.

As a rough analogy, think about how your ears help regulate your speech volume in various situations in life.

The pituitary gland uses its own TSH receptors to sense how much TSH it is secreting, just like we use our hearing to adjust how loudly we are speaking. 

We speak more softly in a conversation, compared to shouting to a friend across a busy street.

TSH “speaks” very softly or not at all when it hears its own voice amplified in its “ears” (its TSH-Receptors).


As most people know, in Graves’ disease, when TSH receptors on the thyroid gland are overstimulated by TSH-Receptor antibodies (TSAb), the thyroid gland may produce too much hormone.

Powerful antibody-driven thyroid stimulation continues long after TSH stimulation is suppressed by excess thyroid hormone.

That’s why the TSH receptor-stimulating antibody used to be called the “Long-Acting Thyroid Stimulator” (LATS), until science realized it was an antibody acting on the TSH receptor.

But TSH receptors are located throughout the body, not just on the thyroid gland.

Therefore, this antibody doesn’t just stimulate the thyroid gland; it can and does attack other organs and tissues, too, and it’s “long-acting” on them as well:

1. SKIN: When TSH receptors on the skin are overstimulated by TSHR antibody, “Graves dermopathy” or Graves’ skin disease is the result, and the effect of this antibody can persist long after the patient is euthyroid or hypothyroid, as shown in a study with a 14 year follow-up (Schwartz, et al, 2002).

2. EYES: When TSH receptors in the eyes are stimulated by TSHR antibody, “Graves’ ophthalmopathy,” or Graves’ eye disease is the result. As in the case of thyroid skin disease, elevated thyroid hormones are not necessary for Graves’ eye disease.

The TSHR antibodies can trigger eye disease long after the Graves’ patient has had a total thyroidectomy and is in a hypothyroid or euthyroid state.

Once triggered by this antibody, Graves’ eye disease can happen even when TSAb antibody is not detectable in serum and thyroid hormone levels are normal. (Tabasum et al, 2016).

3. PITUITARY: When TSH receptors on the pituitary gland itself get overstimulated by these antibodies, what happens?

Not only TSH normone, but also TSH-Receptor antibodies act directly on the TSH receptors on the pituitary gland through the ultrashort feedback loop.

TSH-Receptor antibodies mimic TSH and confuse the pituitary gland about how much it is currently secreting. As a result, TSH can be independently oversuppressed by this antibody attack.


The degree to which TSH is warped by antibody interference depends on which variants of the antibody is or have been dominant (suppressing vs. blocking), the antibody’s current concentration in blood, and the degree to which the antibody may have already resulted in permanent damage to its target organs.

Many TSHR antibody tests measure only the stimulating antibody variant, TSAb.

The test that can measure both blocking and stimulating antibodies at the same time is the TBII test (thyrotropin-binding inhibitor immunoglobulin).

This TBII test is not available in all regions or laboratories, and researchers are arguing for its clinical relevance in autoimmune thyroid diagnosis and therapy. (Diana et al, 2016).

In any case, the antibody measurement is only a snapshot, and antibody levels fluctuate and can disappear. The most important thing to know is that they CAN be there and can return in any autoimmune thyroid patient.

The research proving the long-acting effects of TSH-Receptor antibody interference with TSH results is discussed in more depth in the post “TSH “can be very misleading” during thyroid therapy, say researchers.”


We can learn from this research on the ultrashort feedback loop that the pituitary gland’s secretion of TSH is at the center of more than one feedback loop.

Even beyond these two feedback loops, the pituitary has to be vigilant. Hypersensitive. It must attend to factors that indicate the biological need for adjustments in TSH-stimulation of thyroid secretion.

In human biology, pituitary adjustment of TSH is an ACTIVE force that initiates changes in thyroid secretion rates and ratios, not just a PASSIVE element that responds to thyroid hormone levels. The TSH responds to “feed-forward” stimulation, not just “feedback” signalling.

The hypothalamus and pituitary’s complex regulation of TSH has to receive more input than just thyroid hormone levels so that it can have a regulatory role in health.

Therefore the TSH response, both in theory and in reality, as shown in research, is not always “specific” to thyroid hormone levels.

Yes, doctors are being indoctrinated to believe something false and illogical about the exclusivity of TSH response only to thyroid hormones.

TSH cannot, should not, must not exclusively respond to T3 and T4 in blood and ignore everything else in your body that may require it to drive an increase or decrease in thyroid hormone.

TSH has to be “nonspecific.” Vigilant. Attentive to a wide range of _relevant_ inputs.

We also learn from research that the ultrashort loop is vulnerable. It is vulnerable to irrelevant, foreign, confusing or contradictory inputs — such interference by an antibody that mimics or blocks TSH action on receptors.

Beyond the ultrashort feedback loop, the many common health factors and substances can lower the TSH beyond what it should be given thyroid hormone levels and clinical presentation — see a list and citations in our post Thyrotoxicosis? Many factors can lower TSH.

Ask a mechanical or electrical engineer this question: How trustworthy is a closed feedback loop when it is broken and then it receives similar, but not quite the same, input from a foreign element outside the loop? What does it do with conflicting messages between both pathological and non-pathological inputs?

How accurate can a pituitary be when TSH-thyroid regulation mechanism is broken down by thyroid gland failure, AND when a static thyroid pill dosage attempts to replace a living gland but is insensitive to shifts in daily and seasonal TSH secretion rate, AND when antibodies stimulate the gland and pituitary TSH receptors?

How many inputs into this natural control system need to be abnormal or broken before TSH response is skewed and becomes very abnormal?


In another useful but imperfect analogy, the pituitary TSH, in health, is like the person in the driver’s seat. They want to get from A to B. They aren’t just passively responding to road conditions, signs, and other drivers around them.

A good driver is vigilant.

A poor driver is distracted by checking their mobile phone or talking on the phone while holding it to their ear.

A doctor taking cues only from a TSH driver who is distracted by realistic yet irrelevant antibody input from their “ears” — their TSH receptors — may be entirely incapable of driving the body from point A to B in thyroid hormone levels.

The doctor becomes the mere puppet of a distracted and deranged TSH.

If the patient is thyroidless, then TSH is also a driver whose pressure on the gas pedal no longer adds any fuel to the thyroid gland engine — the TSHR antibody is now driving some pathological processes in some ways that are entirely independent of the relationship between TSH secretion and thyroid hormone supply.

Only thyroid hormones can fuel the high speed metabolism of thyrotoxicosis or make your body run low on gas or crawl along at a snail’s pace.

In thyroid disease and therapy, TSH no longer regulates your thyroid hormone secretion. Thyroid-“stimulating” hormone no longer performs as the “stimulus.” Now, TSH is primarily reactive, and the inputs on TSH response in disease are not the same as the inputs it gets in health.

The medical system wants us all to focus only on the car’s former driver, who is still acting out his role, but is now manipulated by disease and medication factors he wasn’t trained to take into account. 

This TSH driver shouldn’t be the sole guide in charge of thyroid therapy, when TSH is a measure of the complex responses of a single gland to thyroid hormones plus many other influences.


Please, doctors, attend to the fuel gauge and the speedometer on our bodies.

  1. Fuel gauge: Does the TSH response match thyroid levels in blood (T3, T4 — the actual fuel supply and reservoir)?
  2. Speedometer: Do responses to T3 and T4 levels in the rest of the patient’s body result in normal speed or high speed metabolism — Do you see evidence of euthyroidism or  thyrotoxicosis in organs and tissues beyond the pituitary?

Outdated and rigid medical guidelines, oversimplified models, and cost-cutting measures are pushing us to make TSH more and more powerful over therapy decisions and are preventing doctors from measuring Free T3 and Free T4.

Total hormone supply in blood and the ratios between these hormones matter deeply to all tissues in the human body, and a low TSH may be the only anomaly– it’s the response of a single organ, the pituitary.

Powerful institutions are enforcing conformity to this TSH-centric thyroid therapy paradigm, persuading people to believe that thyroid hormone tests are “unnecessary” and that TSH is equally reliable and trustworthy in therapy and disease as it is in untreated, healthy people.

Direct measurement of both major thyroid hormone levels (Free T3 and Free T4) can always give the most accurate data on the degree to which the entire human body beyond the pituitary gland exchanges its T3 and T4 thyroid hormone supply with bloodstream.

In addition, during thyroid therapy, listening to the patient’s body and symptoms can tell you a lot about how far away from that desirable point B they are, the ideal euthyroid metabolic state.


See References for Thyrotoxicosis vs. Low TSH series

Categories: HPT axis, Pituitary gland, TSH hormone

15 replies


  1. References for Thyrotoxicosis vs. Low TSH series – Canadian Thyroid Patients Campaign
  2. TSHR Antibodies can distort TSH secretion – Canadian Thyroid Patients Campaign
  3. Thyrotoxicosis vs. Low TSH – Canadian Thyroid Patients Campaign
  4. As of 2019, still no proof that low TSH causes harm to bones – Canadian Thyroid Patients Campaign
  5. Thyroid therapies: What my life is like in the T3-monotherapy wheelchair – Canadian Thyroid Patients Campaign
  6. Targeting TSH? It’s not as specific or as sensitive as people claim. – Thyroid Patients Canada
  7. LifeLabs BC handout reveals thyroid testing policy failure – Thyroid Patients Canada
  8. Thank you, good thyroid doctors! – Thyroid Patients Canada
  9. The TSH-T3 disjoint in thyroid therapy – Thyroid Patients Canada
  10. 2019 ATA article engages in patient-blaming and doctor-shaming – Thyroid Patients Canada
  11. Thyrotoxicosis vs. Low TSH – Thyroid Patients Canada
  12. New clinical trial of Armour Thyroid is recruiting U.S. patients – Thyroid Patients Canada
  13. Screening for central hypothyroidism during thyroid therapy – Thyroid Patients Canada
  14. The THIRD type of autoimmune thyroid disease: Atrophic Thyroiditis – Thyroid Patients Canada
  15. Infographics for Antibody testing – Thyroid Patients Canada

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