Hypothalamic–Pituitary–Thyroid axis-Negative Fe... - Thyroid UK

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Hypothalamic–Pituitary–Thyroid axis-Negative Feedback Loop

LilLily profile image
6 Replies

Hi Everyone, I'm so confused about the negative feedback that can occur.

What happens during the negative feedback?

When the thyroid hormone is titrated too slowly, what happens? How slow of a titration is too slow?

Because part of the negative feedback loop actually involves the thyroid gland, does this still occur if you do not have a thyroid?

I know most people would have to start at near therapeutic level with a very high TSH. Because my TSH was 151 my titration is pretty quick, 50mcg for 2 weeks, 75 for 1 week, 75/100 switch every-other-day for 1 week, 100 for 1 week, then reassess. I'm now during the week of the 75/100 switch. I'm very sensitive to the hormone hence I can't go up without some titration.

I appreciate any thoughts you may have. :-)

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LilLily
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Nanaedake profile image
Nanaedake

It takes about 6 weeks for thyroid hormone taken by tablet to circulate to all cells and bring your thyroid hormone levels up and then plateau so that a blood test is a reliable indicator of thyroid hormone status at that time. That is why changes up or down are usually in 6 week intervals. The usual advice is to increase by 25mcg at a time.

Some people might need to increase in greater increments if they need to increase hormone levels more quickly and if they are young and otherwise healthy.

When TSH is very high the doctor may order 4 weekly increases to speed the process initially but this could lead to over medication.

silverfox7 profile image
silverfox7

Hi Lily, I’ve just read your history and it hasn’t been an easy time for you. I’m surprised though that as you are so sensitive that you have been fast tracked, I would have thought a more gentle approach would have been more sensible. Please be aware of hyper issues as it’s so easy to over treat someone. As Nanaedake says it takes a full 6 weeks to get each dose increase fully into your system.

LilLily profile image
LilLily in reply tosilverfox7

Thank you so much for the reply. 🙂Yes it has been a tough road but it has gotten so much better.

When he admitted me I was near non-functional. He got me going on 50mcg (infusion) where before I couldn't do 25. I'm so grateful for that.

Considering my weight, he feels I'll at least be on 112-125mcg. Once I've accomplished the 100 all the time (almost there! 😁) I believe he will go more slowly after checking my bloodwork. They've been using hydroxyzine to help me get through the anxiety and I'm happy to say it has worked wonderfully!! It is a non-addictive antihistamine that also helps people with anxiety.

I don't know why I'm so sensitive when I don't suffer anxiety normally, but I'm so grateful for the tools I've been given.

humanbean profile image
humanbean

I'm so confused about the negative feedback that can occur.

What happens during the negative feedback?

My understanding of the HPT axis :

The hypothalamus (H)

The hypothalamus detects the amount of thyroid hormone (T4 and T3) in its own environment and bloodstream, and on the basis of that will increase or decrease the amount of TRH (Thyrotropin Releasing Hormone) it produces.

Decreasing levels of T4 and T3 will increase the output of TRH. Increasing levels of T4 and T3 will decrease the output of TRH.

Note that Thyrotropin is another name for TSH (Thyroid Stimulating Hormone). So you can think of TRH as TSH Releasing Hormone.

The pituitary (P)

The pituitary detects the amount of TRH in its own environment and bloodstream, and on the basis of that will increase or decrease the amount of TSH it produces.

Decreasing levels of TRH will decrease the output of TSH. Increasing levels of TRH will increase the output of TSH .

The thyroid (T)

The thyroid detects the amount of TSH in its own environment and bloodstream, and on the basis of that will increase or decrease the amount of T4 and T3 it produces.

Note that the thyroid produces approximately 20% of the body's entire T3 supply. The remaining T3 is produced by other organs around the body (mainly the liver) by conversion from T4.

Decreasing the amount of TSH will decrease the amount of T4 and T3 produced by the thyroid. Increasing levels of TSH will increase the output of T4 and T3.

...

Note that small changes in any one of the hypothalamus, pituitary or thyroid will, either directly or indirectly, affect the output of the other two. The body makes adjustments all the time, adjusting and fine tuning as activity fluctuates, as food is eaten, as people sleep, and as rhythms in the body change throughout the day and night. The adrenals, for example, have their own HPA axis and output rhythms which produce cortisol. The hormones involved are different at every stage to the HPT axis but the general idea is the same.

...

The above description explains the workings of a healthy system. Now throw a spanner in the works and assume that the thyroid is damaged. It is less able to react to TSH, and so produces less T4 and T3.

The hypothalamus detects the lower levels of T4 and T3 and increases the amount of TRH it produces, then the pituitary increases the TSH, so the thyroid then works harder to produce T4 and T3.

As the thyroid fails the TRH and TSH get higher and higher. Eventually the HPT axis starts to fail completely and the T4 and T3 levels start to fall and nothing can kick the thyroid into working again.

Suppose at this point that the patient's thyroid produces 40mcg of T4 per day. Not nearly enough to be healthy.

...

Now suppose that the patient is prescribed thyroid hormones e.g. Levo. They are prescribed 25mcg Levo per day. This would suggest that the patient now has a total of 65mcg Levo in their body - 25mcg from a pill and 40mcg from their failing thyroid. But this isn't true.

The hypothalamus detects the higher levels of T4 and reduces its output of TRH. The pituitary then reduces its output of TSH. The thyroid reduces its output of T4 and T3 by a substantial amount because it isn't working well anyway. The whole HPT axis is by this time very confused and dysfunctional.

Over time (it might take a few days or a few weeks) the thyroid will reduce its output more and more until the total of the T4 in the pill and the T4 and T3 from the thyroid actually ends up being less than the patient produced by themselves. So the patient ends up being worse off than before they were treated. Since the thyroid is badly damaged and cannot be coaxed and bullied into producing more thyroid hormones the answer to the problem is to take more Levo.

...

If someone has their thyroid removed or killed off with RAI then the hypothalamus and the pituitary have to work solely from the T4 taken in pill form. When treating a thyroidless patient with T4, the amount of T3 in their body will never equal what they had before removing or killing their thyroid. Few people (if any) can create enough T3 by conversion from T4 to replace what their thyroid produced when it was healthy. This is why people with no thyroid should always be treated with T4 and T3, NDT, or possibly just T3 only, depending on which suits the patient best. But doctors have got their heads in the sand, fingers in their ears, and their arses in the air while they sing "La, La La, I can't hear you!"

LilLily profile image
LilLily in reply tohumanbean

Wow!! Thank you so much for your response and knowledge!! This is wonderful!

guysgrams profile image
guysgrams

humanbean is there a paper that spells this out? Sure would like to take this to my Endo!

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