Thyroid Hormone and Negative Feedback - clarification needed

[MedLover25]

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On a USMLE World question:
A guy took levothyroxine to lose weight (basically induced a state of hyperthyroidism in himself). They then asked what is the most likely cause of the low blood TSH level in this patient?

They claim the answer is "Free T3 level" because "T4 is converted to T3 in peripheral tissues. When circulating thyroid hormone levels increase, free T3 has the most important role in negative feedback control of TSH. Free T3 causes downregulation of TRH receptors in the Anterior Pituitary and the decreased sensitivity to TRH causes thyrotrope ceclls to produce less TSH"

However, according to Kaplan (and they made a big deal about this):
**The Pituitary Gland monitors T4 in the Blood** it does NOT monitor T3 level in the blood.

The Release of TSH depends on:
1) Level of T4 in the blood
2) Level of T3 in the pituitary gland (T4 gets converted to T3 within the gland, which then causes it to produce less TSH (similar explanation as above)).

So, who is correct in this situation? I'm more inclined to go with the Kaplan book and video over U-world. Anyone know for sure?

 

[ENThopeful]

goljan says both t4 and t3

thats a though q

 

[ENThopeful]

http://www.ncbi.nlm.nih.gov/pubmed/19179434

According to this paper
"As noted above, circulating T4 is converted to T3 by D2 in tanycytes. The balance
of evidence suggests that T3 then gains access to the TRH neuron via the MCT8
transporter. After T3 enters TRH neurons in the PVN, regulation occurs at two levels:
expression of the preproTRH transcript and processing of proTRH into the mature TRH peptide. The regulation of TRH gene expression by T3 occurs mostly through TRβ2,
presumably via a direct mechanism. It is also possible that T3 acts in the signaling
pathway of TRH gene expression via other hypothalamic nuclei since TRβ2 is also
expressed in the arcuate and ventromedial nuclei, and both nuclei can alter the set-point of TRH expression to fasting. "

Thats for TRH

http://www.sciencedirect.com/scienc...d=687830&md5=b54af9a58416d8e3a5a811929467e495
This article states:
"T3 action is mediated by two types of nuclear receptor, encoded by the TRα and the TRβ genes, respectively. These receptors act directly on gene transcription, mainly as retinoid-X-receptor (RXR) heterodimers ...... For example, TSH feedback regulation is lost completely only when both TRα and TRβ are deleted "

The above is the culmination of 12 minutes of research so take it with a grain of salt.

I personally think its a bad question.. was it made recently?

 

[phassett74]

Not sure if you can get to this, but this is via Kronenberg: William's Textbook of Endocrinology (essentially endo Harrison's):

http://www.mdconsult.com.ezproxy.ch...4160-2911-3..50012-1--f8.fig?tocnode=54106482

The picture is good, and figure below it describes the following: Figure 10-8 Role of T4 and T3 in the feedback regulation of TRH and TSH secretion. Secreted T4 must be converted to T3 to produce its effects. This conversion may take place in tissues such as the liver (L), kidney (K), and thyroid (T) catalyzed by D1. D2 is present in human thyroid (T), skeletal muscle (SM), possibly cardiac muscle (CM) and the pituitary and hypothalamus.

The picture demonstrates the conversion of T4 to T3 in hypothalmus & pituitary by D2

So it seems as though the crux of the matter, played upon in far too much detail by USMLEWORLD, is that one's TSH is exquisitely sensitive to feedback via circulating T4 - even though that T4 is converted to T3.

 

[ENThopeful]

Curious:

What were the answer choices? You may end up with this answer just because of logical deduction. If it came down to t4 vs t3, the answer I would put down is t3, just cause t4 is the prohormone.

Forget what kaplan says

 

[MedLover25]

Curious:

What were the answer choices? You may end up with this answer just because of logical deduction. If it came down to t4 vs t3, the answer I would put down is t3, just cause t4 is the prohormone.

Forget what kaplan says

Answer choices were:
a-f
T3 insensitivity
Inhibin Level
Endogenous T3 conversion to T4
Protein bound T4 level
Free T4
Free T3

Yes, T4 is "inactive" and T3 is "active" - so it makes sense that T3 would control TSH production. BUT, according to Kaplan, this only occurs once T4 is converted to T3 within the gland itself. They said that this is a pretty typical question and that they usually switch it up by asking "plasma levels" or "levels within the gland"

 

[MedLover25]

Not sure if you can get to this, but this is via Kronenberg: William's Textbook of Endocrinology (essentially endo Harrison's):

http://www.mdconsult.com.ezproxy.ch...4160-2911-3..50012-1--f8.fig?tocnode=54106482

The picture is good, and figure below it describes the following: Figure 10-8 Role of T4 and T3 in the feedback regulation of TRH and TSH secretion. Secreted T4 must be converted to T3 to produce its effects. This conversion may take place in tissues such as the liver (L), kidney (K), and thyroid (T) catalyzed by D1. D2 is present in human thyroid (T), skeletal muscle (SM), possibly cardiac muscle (CM) and the pituitary and hypothalamus.

The picture demonstrates the conversion of T4 to T3 in hypothalmus & pituitary by D2

So it seems as though the crux of the matter, played upon in far too much detail by USMLEWORLD, is that one's TSH is exquisitely sensitive to feedback via circulating T4 - even though that T4 is converted to T3.

Thanks for the research. I couldn't access the link, but thanks for helping out.

I could understand asking the question if you put either T3 or T4 as answer choices (making you pick "the best answer") but putting two correct answers, and then explaining that circulating T3 is what's responsible (when its actually circulating T4) threw everything off. Hopefully they respond back to my email and can correct the question (either the answer choices and/or the explanation)

 

[ENThopeful]

Answer choices were:
a-f
T3 insensitivity
Inhibin Level
Endogenous T3 conversion to T4
Protein bound T4 level
Free T4
Free T3

Yes, T4 is "inactive" and T3 is "active" - so it makes sense that T3 would control TSH production. BUT, according to Kaplan, this only occurs once T4 is converted to T3 within the gland itself. They said that this is a pretty typical question and that they usually switch it up by asking "plasma levels" or "levels within the gland"

Ahh, I understand your train of thought

so you are saying its

Free T4 (subsequently converted to t3)
vs.
Free T3 (directly acting on the pituitary and PVN of the hypothalmus)

Its a tough Q and I dont know how I would have answered that.

By the way, when are you sitting for the test? As I recall you started studying awhile back

 

[MedLover25]

Ahh, I understand your train of thought

so you are saying its

Free T4 (subsequently converted to t3)
vs.
Free T3 (directly acting on the pituitary and PVN of the hypothalmus)

Its a tough Q and I dont know how I would have answered that.

By the way, when are you sitting for the test? As I recall you started studying awhile back

End of march. Started studying 2nd week or so of January - but actually started serious studying maybe 2.5 weeks ago.

 

[ENThopeful]

ahhh

best of luck! sounds like you are on the right track

 

[phassett74]

MedLover,

Keep in mind if this is your first time with USMLEWORLD, the whole idea is to "overlearn" the topic in such excruciating painful detail that the real test seems easy in comparison. The fact that it is making you review this topic and truly understand the mechanism, is far more than you will be required to do on the real test.

Basically, as interesting as this is, you would not likely see this question on step 1.

I am really not sure where they get some of the questions they get on that system, but would guess that you are dealing either with a misunderstanding of a topic, or just poor phrasing/structuring of the question/answer.

Best of luck.