Lecture 2 thyroid hormones Flashcards
Learning Outcomes
- [Similar structure to remaining endocrine lectures]
- -Describe the location, gross function & morphology of the thyroid gland
- -Thyroid hormones
Feedback loop
Synthesis & role of iodine
Secretion
Regulation by TSH
Activity
-Explain the pathophysiology underlying disorders of thyroid function
Relates to other modules (e.g. Pathology & Medicine)
Tests understanding of basic physiology (many symptoms are predictable if basic mechanisms are understood)
Anatomy/Function of the Thyroid Gland
-Adheres to the trachea, just below the larynx
-Tissue mass: 10-20g
-2 flat lobes connected by an isthmus
*Usually, right lobe > left
-Secretes thyroxine (T4), tri-iodothyronine (T3) and calcitonin
*T3, T4: iodine containing hormones
acting throughout the body
*Calcitonin: regulates plasma
calcium (see later lecture)
Morphology of the Thyroid Gland
-
*Functional unit = follicle
-Basement membrane anchors
follicle to connective tissue
-Epithelial outer layer (“follicular
cells”): secrete T3 and T4
-Central colloid-filled cavity
-Changes morphology between
active and inactive states (↑ activity
→ ↓ colloid storage)
*Colloid: mainly consists of glycoprotein (thyroglobulin)
*C-cells present in basement membrane and between follicles
-Secrete calcitonin
*Rich blood supply
-Approx twice kidney blood flow
-Regulated by ANS
lumen- is made of colloid
thyroid epithelial cells are follicular cells
-c-cells make calcetonin
-we also find blood capillaries because hormones are defined as signalling molecules that act through the blood, One thing that you will find of any endocrine tissue is it has a really rich, dense capillary network supplying it with blood. And that makes intuitive sense because hormones are secreted through the blood. And therefore, if you are a tissue whose main job in the body is to produce and secrete hormones that make sense, you’ve got a really dense blood supply because it’s the blood, which is the thing that carries your hormone signal to the rest of the body.
- And you will also find various nerve terminals, such as sympathetic nerve terminals here, because the sympathetic nervous system can also regulate thyroid hormone production.
Thyroid Feedback Pathways
Hypothalamus
↓Thyrotrophin Releasing Hormone (TRH
Anterior Pituitary
↓ thyroid stimulating Hormone (TSH)
Thyroid
↓(T3/T4)
→→ → → → → → → → → → → → ↑ (pathways feedback up to the anterior pituitary and hypothalamus)
the T3/T4 hormones have their effects all around the body, particularly in terms of things like growth and metabolism. But what they also do is close the negative feedback loop.
And T3 and T4 will inhibit both TRH from the hypothalamus and TSH from the anterior pituitary- classical feedback loop
Synthesis of Thyroid Hormones (T3/T4): Thyroglobulin & Iodination
*Two components are necessary: the glycoprotein thyroglobulin and iodine, which comes from the diet
*Thyroglobulin = 670kDa glycoprotein- very large glycoprotein, - a glycoprotein is a protein with a sugar molecule attached or has oligosaccarides attached to it
—-Comprises 2 peptides of 330kDa and carbohydrate moieties covalently bound to them
—–Synthesised in follicular cell rough endoplasmic reticulum, package and maturation occurs in the Golgi complex found within the cytoplasm, it is then released into the lumen of the thyroid follicle by exocytosis
——Packaged into vesicles and released into lumen by exocytosis
Stored as colloid
*Iodination
-T3 and T4 require dietary iodine (≈
75mg/day; 140µg/day recommended
in UK)- required via our diet only
-“Iodide trapping”: Inorganic iodide
enters follicular cells via Na/I co-
transporter- this requires an active transport against the concentration gradient to maintain a low intercellular Na+ concentration inside the cell
* so we have the bilayer of the cell membrane on the outside of the follicular cell, And then we’ve got this tube that sits through that membrane, And this represents an ion channel. And it’s an ion channel that Co-transports sodium ions and iodide ions. so, first of all it requires an active energy dependent process from the follicular cells, And what they do is using energy. They actively pump sodium ions from the cytoplasm of the cell into the extracellular space. So it’s acting against a concentration gradient to set up a high concentration of sodium outside the cell and a low concentration of sodium within the cell cytoplasm. What then happens is sodium wants to flow back into the cell down its concentration gradient, but it can only do this through these specific ion channels, So to try and restore this concentration balance, Sodium ions flow back into the follicular cell down its concentration gradient, But when the sodium ions come back into the cell, each sodium ion pulls an iodide ion with it. so the iodide gets into the follicular cell because it’s pulled into the cell As sodium flows down its concentration gradient. Okay. And that is the process of iodide trapping.
- iodide is then transported across the cell membrane and released into the lumen of the follicle and there it covalently binds with the thyroglobulin to form the colloid complex that sits in the lumen of the thyroid follicles
and how this is released is that the colloid sitting there in the lumen at the follicle, when the thyroid follicular cell is stimulated to release its hormone, it actually engulfs some of the colloid from the thyroid lumen by endocytosis, So it takes up, the vesicle containing colloid from the lumen into the cytoplasm of the follicular cell. That vesicle containing the colloid then fuses with lysosomes. lysosomes are structures within the cell that are packed full of enzymes, And these enzymes within the lysosomes digest the colloid that’s being brought into the cell. And these digestion products of colloids include the hormones T3 and T4 and also various other waste products, which are then recirculated back in to aid the formation of new thyroglobulin. But in terms of the endocrine status, when the colloid is degraded by the lysosomal enzymes, it causes the production of T3 and T4.
T3/T4 are part of that lipophilic family that includes the steroids, because T3 and T4 are lipophilic, there is no active secretory process. They are able to diffuse passively across the cell membrane of the thyroid follicular cell into the blood. but because they’re lipophilic. They don’t dissolve readily within the blood plasma. And therefore you will find them almost entirely bound to carrier proteins within the blood. These carrier proteins enable them to be dissolved within the blood and therefore become soluble. So that is how colloid is important for the production of T3 and T4.
-Iodine transported → follicle lumen
-Iodination of free tyrosine residues of thyroglobulin
-Hydrolysis of iodinated thyroglobulin → T3/T4
-Some T3 synthesised, but approx
20-fold more T4
-Thyroid stores several weeks supply
of T3/T4
Summary of Synthesis and Secretion of thyroid hormones
Synthesis and Secretion of Thyroid Hormones:
The thyroid gland produces two main hormones, thyroxine (T4) and triiodothyronine (T3), which are crucial for regulating metabolism, growth, and development. Here’s a summarized overview of their synthesis and secretion process:
- Iodide Uptake:
Iodine from the bloodstream is actively transported into the thyroid follicular cells via the sodium-iodide symporter (NIS) located on the basolateral membrane of the follicular cells. The iodide trap. - Iodide Oxidation and Organification:
Once inside the follicular cell, iodide is transported to the apical membrane of the cell, where it is oxidized to iodine by the enzyme thyroid peroxidase (TPO).
The oxidized iodine is then covalently attached to the tyrosine residues on thyroglobulin (a large glycoprotein produced by the thyroid) in a process called organification.
This leads to the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT). - Coupling of Iodinated Tyrosines:
Two DIT molecules couple to form thyroxine (T4), or one MIT and one DIT molecule couple to form triiodothyronine (T3). This coupling is also catalyzed by TPO.
These iodinated thyroglobulin molecules are stored in the colloid of the thyroid follicles. - Endocytosis of Thyroglobulin:
When thyroid hormones are needed, thyroglobulin is taken back into the follicular cells by endocytosis from the colloid. - Proteolysis of Thyroglobulin:
Inside the follicular cells, thyroglobulin is broken down by lysosomal enzymes, releasing T3 and T4 into the cytoplasm. - Secretion of Thyroid Hormones:
The free T3 and T4 are then secreted into the bloodstream via diffusion.
The ratio of secreted T4 to T3 is about 90% T4 and 10% T3. However, T3 is the more active form, and T4 can be converted to T3 in peripheral tissues by deiodinase enzymes. - Transport in the Blood:
Once released into the bloodstream, thyroid hormones are mostly bound to transport proteins like thyroxine-binding globulin (TBG), transthyretin, and albumin, with a small fraction remaining free and biologically active.
Regulation:
The synthesis and secretion of thyroid hormones are regulated by the hypothalamic-pituitary-thyroid axis:
The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH).
TSH stimulates the thyroid gland to produce and release T3 and T4.
Elevated levels of T3 and T4 exert negative feedback on both the pituitary and hypothalamus, reducing TRH and TSH release.
Summary:
Iodide uptake into thyroid follicular cells.
Iodine is oxidized and attached to thyroglobulin.
MIT and DIT couple to form T3 and T4.
Thyroglobulin is endocytosed and broken down, releasing T3 and T4.
T3 and T4 are secreted into the bloodstream, where they are mostly protein-bound.
Thyroid hormone secretion is regulated by the hypothalamic-pituitary-thyroid axis via TRH, TSH, and negative feedback from T3 and T4.
picture breakdown-
in the light blue colour This represents a thyroid follicular cell. So we’ve got a whole cell in the middle. And then we’ve got a bit of a cellalong the sides, at the top in pink this is the lumen of the thyroid follicle, And this is where the colloid, um, is stored. And what this diagram is showing you is the entire process of T3 and T4 production and release. So we start on the bottom left of the slide here we’ve got this black circle This represents the sodium iodide um transporter protein. And this is the thing that’s essential for iodide trapping the highly specific mechanism that enables the thyroid tissue and only the thyroid tissue to take up iodine. So the way in which this works, sodium ions are actively pumped from the cytoplasm into the extracellular space They then flow back down their concentration gradient back into the cell. And then when the sodium ions flow back into the cell. They pull iodide ions with them through this ion channel. The iodine then travels across the cell and into the colloid, where it’s covalently bound to a glycoprotein called thyroglobulin. thyroglobulin is produced in the same basic way that any protein is. You get transcription of the mRNA, which is then translated at the rough endoplasmic reticulum, You get packaging and processing within the Golgi apparatus and then little vesicles bud off and are released into the lumen by a classical exocytosis pathway. The colloid is then formed by the iodine and thyroglobulin covalently binding together. When the cell wants to release a hormone, what it does is it takes up some of this colloid by endocytosis, so you get a vehicle of colloid that’s taken into the cell cytoplasm, shown here by this pink, circle, The vesicle containing the colloid fuses with a lysosome. Lysosome is shown by the yellow circle, The enzymes within the lysosome digest the colloid, and two of the products of the colloid being digested are the molecules T3 and T4, Because they are lipophilic. They diffuse passively across the cell membrane into the blood, and also because they are lipophilic, they are found almost entirely bound to carrier proteins within the blood
Roles of TSH in Thyroid Function
TSH stimulates pretty much every single component of that T3, T4 synthetic pathway, by binding through its receptors, TSH stimulates all of these different components
- It causes an increase in iodide trapping by making the follicular cells produce more of these sodium iodide cotransporter molecules.
-It increases the rate of thyroid globulin synthesis
- It increases the rate at which the thyroglobulin is iodinated (joined to iodine) in the lumen to form colloid
- It also causes an increase in the uptake of colloid from the lumen back into the follicular cells
- So all of the different stages within that T3 T4 synthetic pathway are all stimulated by TSH
- It’s also essential for the maintenance, of the thyroid tissue itself
- the size of the thyroid gland is proportional to the amount of TSH that we have.
- If we have more TSH, the thyroid gland tends to get bigger.
- If we had no TSH, then the thyroid gland actually atrophies and dies
- So the TSH doesn’t just stimulate the biochemical pathways within the thyroid, it actually maintains the size of the thyroid tissue itself.
*TSH receptors on follicular cell surface by binding to its receptors results in:
-GPCR coupled to adenylate cyclase
*Stimulation of hormone synthesis
-↑ Iodide trapping via Na/I co-
transporter
-↑ Thyroglobulin synthesis
-↑ Iodination of thyroglobulin
*Stimulation of hormone secretion
-↑ Uptake of colloid by follicular cells
*Necessary for thyroid gland maintenance
-Gland rapidly atrophies in absence
of TSH!
Action of Thyroid Hormones
What is the physiological function of T3, T4. What do they do. Well I mentioned that we get about 20 fold more T4 secreted than T3. However, T3 is the biologically active form, SO why is the thyroid gland primarily secreting the inactive form of its hormone?
- there’s actually a very good reason for that. And the reason is that by secreting the inactive form of the thyroid hormone, it enables cells around the body to choose how sensitive they are to thyroid hormone secretion, because cells in the body are capable of producing an enzyme called Deiodinase 2. Deiodinase literally means removal of an idodine, and this converts the inactive T4 to the active T3. so the deiodinase 2 a cell expresses, the more sensitive it is to the hormones produced by the thyroid gland
- So because the thyroid secretes the inactive form, it’s enabling cells to regulate how sensitive they are to its hormonal output, Likewise, if a cell doesn’t express the deiodinase 2 enzyme the thyroid Hormones are there but won’t really have any effect because the cell can activate it.
- thyroid hormones act by regulating the transcription of multiple genes. And note the phrase multiple genes. It’s not just 1 or 2.
- It’s hundreds, at least hundreds of different genes within a target cell are regulated by these thyroid hormones.
- - Some will have the transcription increased. Some will have their transcription decreased
- The T3 acts by working through the nuclear receptor/intracellular receptor mechanism, to regulate the transcription of hundreds of different genes within that target cell. In general, the genes are regulating metabolic physiology within that cell. So for example, protein metabolism is particularly sensitive to thyroid hormones but also BMR, that stands for basal metabolic rate. thyroid hormones are a strong stimulator of our basal metabolic rate. over a hundred different enzyme systems are actually sensitive to thyroid hormones and together increase our basal metabolic rate. The thyroid hormone is acting through a really complex network of different molecular pathways within its target cells.
*T3 has far greater activity than T4
-Intracellular conversion of T4 to T3
by deiodinase 2
-Deiodinase 2 provides a mechanism
by which cells control sensitivity to
thyroid hormones
*Act as “growth factors” in multiple tissues
*Regulate gene transcription
-Cytoplasmic receptors → nucleus
-Effects take hours-days
*Induce specific tissue effects; also ↑ O2 consumption and heat production of whole body
-Altered protein metabolism
-↑ BMR (>100 enzyme systems
sensitive to T3)
-↑ activity of Na+/K+-ATPase
-↑ glucose uptake & lipolysis
Abnormal Thyroid Function
like in most cases where we get abnormal endocrine function, we can either have too much of the hormone produced or too little of a hormone produced.
So we’re going to start off by looking at what’s called hypothyroidism, which is an overactive thyroid where we get too much of a hormone produced, sometimes referred to as being thyroid toxicosis.
And the main example of a hypothyroidism is a disease called graves disease.
And graves disease is an autoimmune condition. And in graves disease, the body produces antibodies,
and these antibodies bind to TSH receptors and stimulate the activity of these receptors independent of the hormone TSH.
So in graves disease, antibodies are made which cause a permanent long term activation of the thyroid follicular cells by activating the TSH receptors.
So what are the symptoms?
Well first of all we have a symptom called goitre, which is probably one of the most obvious, external physiological signs.
And goitre is an enlarged thyroid gland.
Now, if you remember I mentioned a couple of slides ago, the TSH doesn’t just stimulate all the biochemical pathways within the follicular cell.
It also maintains the activity of the tissue and increases the size of the tissue.
So if you have too much stimulation of THC receptors, we get increased growth of the thyroid.
Normally you can’t see the thyroid externally, but in severe cases it can get to the size of up to about a tennis ball.
So you get a really large lump in severe cases at the front of the neck.
So that’s goitre. You also get something called exophthalmos, which is the other main symptom that you might be able to see externally. And this is a protrusion of the eyeballs. And the reason for that is because you get an increase in the pressure within the the ocular socket.
This causes the eyebrows to go back and the eyes to be pushed forward a little bit.
Um, and so you get this look of a kind of intense stare from these individuals because
literally they’ve got their eyeballs are being pushed forward a little bit.
So those are the two classical symptoms that you may be able to see externally in a severe case.
What happens in terms of your physiology. Well remember that thyroid hormone stimulates metabolic rate.
So in the case of hypothyroidism where you have too much of these hormones produced in an uncontrolled fashion,
it makes sense that your basal metabolic rate will be very high.
And that is indeed true. So then these individuals have a high basal metabolic rate and a high heart rate.
And because of their high basal metabolic rate, they tend to have quite extreme weight loss.
So how can you treat this? How can you treat it?
You want to basically remove the activity of the thyroid gland itself.
And there are two main ways in which that can be done. First of all is you can surgically remove some of the thyroid tissue.
Um, but there is another way which can be used, and that is to make use of the iodide trapping mechanism of I explained,
because it is only specifically taken up by the thyroid and no other part of the body.
You can treat these patients with a radioactive form of iodine.
And that radioactive iodine will locate very specifically in the thyroid tissue and nowhere else in the body,
which means it’s relatively safe in that localised concentration of radioactivity will actually destroy some of that excess thyroid tissue.
So it’s a non-surgical way of actually getting rid of excess thyroid tissue.
That’s hyperthyroidism.
What happens in hypothyroidism where we have an underactive thyroid?
Well, there are two main causes for this. One is the iodine deficiency.
So remember the iodine is is essential for colloid production.
And therefore T3 and T4 production. And iodine must come through the diet.
We can’t get it through any other source.
So if we have a dietary insufficiency of iodine over a long period of time, we use up all the colloid that we store in our thyroid follicles.
We can’t make any T3 or T4, and therefore the amounts of thyroid hormone we produce goes down.
But one of the symptoms of this is that we get a goitre.
And I’ve already just mentioned that goitre is a symptom of hypothyroidism.
So how can we get goitre in hyper and hypothyroid states.
Well this can be explained by thinking about negative feedback loops.
If you are insufficient in iodine, you cannot make T3 and T4 because you haven’t got part of the molecular make up of those hormones.
So if you can’t make T3 and T4, you reduce the negative feedback loop,
which means you get more TRH produced from the hypothalamus and more TSH secreted from the pituitary gland.
So even though you can’t make T3 and T4 part of the negative feedback loop, physiological response is you get an increase in TSH production,
=and TSH will still be able to act on its receptors on the thyroid follicle and increase the size of the thyroid gland.
It’s just unable to stimulate the hormone production because there’s no iodine.
Without the iodine, you don’t get the hormone.
So in this case, you can get goitre from one of the forms of hypothyroidism, as well as being a symptom of hypothyroidism.
A good example of how understanding negative feedback can explain something which initially sounds, a little bit paradoxical.
So that is one way in which you can be hypothyroid by having insufficient dietary iodine for a long period of time.
But there is another cause of hypothyroidism which has a completely different cause.
And this is a disease called Hashimoto’s disease. And this is another autoimmune condition.
But in this case, due to the antibodies that the body produces, the cosequences are completely different.
In graves disease, the antibodies bind and stimulate TSH receptors, causing hyperthyroidism in Hashimoto’s disease.
You get different antibodies produced and these actually stimulate the immune system to destroy the thyroid tissue itself.
So in Hashimoto’s disease, you get, um, physical destruction of the thyroid tissue caused by an autoimmune, response.
Okay. So in this case there are two different ways in which we can have an underactive thyroid.
What are the diseases associated with this.
Well we get two different types of disease depending upon what developmental stage the hypothyroidism began.
And there were other examples of this. you can have a different disease
depending upon whether that disease initiated during childhood or during adulthood.
In adults, if you grow up and develop normally but then become hypothyroid whilst you are an adult,
you get symptoms including a decrease in that basal metabolic rate.
That should be pretty obvious. Thyroid hormones stimulate basal metabolic rate.
If you don’t have enough thyroid hormone, you get a decrease in that basal metabolic rate.
You also get a decrease in mental function and therefore lethargy.
So that all ties in, I think very nicely and very simply with the basic idea that thyroid hormones stimulate your metabolism.
However, if hypothyroidism occurs in childhood and is untreated here,
you get additional problems because thyroid hormones are also involved in the developmental process,
particularly in terms of growth of the body and brain development.
So individuals who are hypothyroid and untreated in childhood, they have a disease called cretinism.
and these patients tend to be physically smaller than average because they don’t have that impact of thyroid hormones on growth as they go through childhood.
They also tend to have mental retardation, which reflects the fact that thyroid hormones are involved in mental, physiology as well.
If they don’t have sufficient thyroid hormone, as they are growing and developing,
they get long term mental retardation as well as a decrease in their physical size.
So how can you treat this? Well, the way in which you treat a decrease in normal hormone production is pretty much the same,
irrespective of what that hormone is, and that is to give hormone replacement.
we can give hormones as replacement when any part of the endocrine system doesn’t produce enough hormone.
And so the way in which you do this is by giving, um, a tablet of thyroxine or T4.
And I know elderly members of my family have had thyroid tablets.
You may well know members of your family who have thyroid tablets.
It’s not an uncommon thing. And so simply you treat the fact that the body isn’t producing enough of these hormones by
giving them a tablet that contains an increased amount so they get the hormone through,
um, the tablet, rather than through the thyroid gland.
But the key point again is if you understand the basic physiology of these thyroid hormones and negative feedback loops,
you should be able to predict most of what is on this slide
*Hyperthyroidism (thyrotoxicosis)
-e.g. Grave’s disease (autoimmune –
antibodies activate TSH receptor?)
-Symptoms inc:
-goitre (enlarged thyroid)
-exophthalmos (protrusion of eyeballs)
-↑ Basal Metabolic Rate (BMR) & heart rate
-weight loss (due to ↑ BMR)
-Treatment: surgical removal or 131I ingestion
*Hypothyroidism
-Causes
-Iodine deficiency → ↓ T3 feedback
→ ↑ TSH → goitre
-Hashimoto’s thyroiditis
(autoimmune) → thyroid
destruction
*Myxedema: adults
-Iodine deficiency → ↓ T3 feedback → ↑ TSH → goitre
-Hashimoto’s thyroiditis (autoimmune) → thyroid destruction
*Myxedema: adults
Symptoms inc. -facial swelling
-↓ mental function
- lethargy
-↓ BMR & heart rate
*Cretinism: congenital, children
Symptoms inc. -mental retardation
-↓ body growth
*Treatment: hormone replacement (T4) or iodine supplements (in deficiency states)
*Diagnoses confirmed by assay of plasma T3 and T4
Summary
We started off by looking at the anatomy and the morphology of the thyroid tissue.
And the key point here is that the main functional structure within the thyroid gland, the structures called follicles,
which are spherical structures that sit within the cellular tissue and the follicles, have an important structure in the middle.
They have a lumen which is filled with a substance called colloid.
Colloid is a precursor for the hormones T3 and T4.
Sitting around this lumen of colloid, we have a ring of cells called follicular cells.
And these follicular cells are the key cells involved in T3 and T4 production. And there’s a relatively complex mechanism by which these hormones are produced and secreted.
But it all depends upon basic cell biology that you should already know.
The one thing that’s a little bit different is iodide trapping.
And this is the specific mechanism that the thyroid follicular cells have for taking up iodine.
What happens here is the follicular cells actively pump sodium ions from the cytoplasm into the extracellular space.
These sodium ions flow back into the cell down their concentration gradients.
As they do so, they pull iodide ions with them. So this very specifically brings iodine into the thyroid cells.
Iodine then gets transported into the lumen of the thyroid, where it covalently binds to a glycoprotein molecule called thyroglobulin.
And this iodine-thyroglobulin complex is what we call colloids.
When the cell needs to secrete the hormones, it takes up colloid by endosytosis, the vesicle containing the colloid fuses with lysosomes.
The enzymes within those lysosomes digest the colloid, and two of the products of that digestion are T3 and T4.
Because they are lipophilic, they diffuse passively out of the cell.
There’s no active secretory process, and they are found bound to carrier proteins.
Once they get into the blood, these cells again, because theyre lipophillic when they get to the target cells,
they can diffuse across the membrane to the target cells and bind to intracellular receptors.
And they act by regulating the transcription of hundreds of different genes within their target cells.
And the net simplistic response of that is that they increase basal metabolic rate.
*Functional thyroid unit = follicles
*Follicular cells produce T3 and T4
-Dietary iodine necessary for synthesis (“iodide trap”)
-Iodination of thyroglobulin & hormone synthesis in lumen of follicle
-Thyroglobulin degradation in follicular cell, then hormone secretion
-Multi-step regulation by TSH
*Secreted hormone bound to plasma proteins (esp. TBP)
*Target tissues
-Convert most T4 to T3
-Multiple tissue responses
What would be the likely effect of 5 days without dietary iodine on,
TRH, TSH, T3, T4
If someone goes 5 days without dietary iodine, the following effects on TRH, TSH, T3, and T4 levels would likely occur:
- T3 and T4 Levels:
T3 and T4 levels would decrease. Iodine is a crucial component for the synthesis of thyroid hormones (T3 and T4). Without sufficient iodine, the thyroid gland would not be able to produce adequate amounts of these hormones.
However, after just 5 days without iodine, the decrease might be mild since the body has some stored iodine reserves. - TSH Levels:
TSH levels would increase. As T3 and T4 levels fall, the anterior pituitary detects this decrease and responds by secreting more thyroid-stimulating hormone (TSH). TSH stimulates the thyroid to increase hormone production. In the absence of sufficient iodine, the thyroid is unable to keep up with TSH stimulation, leading to elevated TSH levels. - TRH Levels:
TRH levels would increase. As T3 and T4 levels decrease, the hypothalamus would sense the drop and increase its production of thyrotropin-releasing hormone (TRH) to stimulate the pituitary to release more TSH. This increase in TRH is part of the negative feedback loop attempting to restore normal thyroid hormone levels.
Summary:
T3 and T4: Would decrease due to insufficient iodine for hormone synthesis.
TSH: Would increase to stimulate more thyroid hormone production.
TRH: Would increase in response to low T3 and T4 levels.
The overall result is an attempt by the body to compensate for low thyroid hormone levels by stimulating the thyroid gland to produce more, but this is limited by the lack of available iodine.
How might a loss of deiodinase 2 activity affect physiology?
A loss of deiodinase 2 (DIO2) activity would significantly impact thyroid hormone regulation, particularly the conversion of the inactive T4 (thyroxine) to the active T3 (triiodothyronine). Deiodinase 2 is responsible for converting T4 into T3 in peripheral tissues like the brain, pituitary, muscle, and brown fat.
Physiological Effects:
- Reduced Active T3:
Without DIO2, there would be less conversion of T4 to T3, leading to lower levels of T3, the more potent thyroid hormone responsible for most of the hormone’s biological effects (like regulating metabolism, growth, and development).- symptoms would be similar to someone that has hypothyroidism
2.Compensatory Increase in T4:
The body may respond by increasing T4 production due to feedback from the hypothalamus and pituitary, but this would still not compensate fully because T4 alone is less active than T3.
- Impaired Metabolic Function:
Lower T3 levels would impair the body’s metabolic processes. Symptoms could include weight gain, fatigue, cold intolerance, slowed heart rate, and cognitive issues.
- Hypothyroid-Like Symptoms:
Even though the thyroid gland may still produce normal amounts of T4, the lack of conversion to T3 can lead to symptoms similar to hypothyroidism.
- Impact on Specific Tissues:
Tissues that rely heavily on DIO2 for local T3 production, such as the brain and pituitary, may experience reduced T3 signaling, leading to cognitive dysfunction, mood changes, and impaired feedback on the hypothalamic-pituitary-thyroid axis.
- Disruption of Negative Feedback:
Lower T3 levels can impair feedback regulation, leading to an increase in TSH levels. This elevated TSH might cause thyroid gland overstimulation in an attempt to increase T3 levels.
Summary:
Loss of deiodinase 2 activity would reduce the production of active T3 from T4, leading to symptoms associated with hypothyroidism and metabolic dysfunction, despite potentially normal levels of circulating T4.
What would be the effect of iodine supplementation in Hashimoto’s disease?
a patient with Hashimoto’s disease giving them iodine supplements in their diet would be very ineffective because their problem is they haven’t got a thyroid gland in the first place
Hashimoto’s disease, also known as Hashimoto’s thyroiditis, is an autoimmune condition in which the immune system attacks the thyroid gland, leading to chronic inflammation and eventual hypothyroidism (underactive thyroid). The thyroid gland becomes less capable of producing sufficient thyroid hormones (T3 and T4), and treatment typically involves thyroid hormone replacement.
The effect of iodine supplementation in someone with Hashimoto’s disease can vary and is a subject of careful medical consideration due to the complex relationship between iodine and thyroid function.
Potential Effects of Iodine Supplementation in Hashimoto’s Disease:
- likelihood is no impact as they lack a functioning thyroid to make use of the iodine
1.Worsening of Autoimmunity:
Excess iodine can exacerbate the autoimmune response. High levels of iodine may stimulate further autoantibody production (such as thyroid peroxidase antibodies, or TPO antibodies) in patients with Hashimoto’s, worsening the attack on the thyroid gland. This can accelerate thyroid tissue destruction and worsen hypothyroidism.
- Increased Risk of Hypothyroidism:
In individuals with Hashimoto’s disease, high iodine intake may overwhelm the thyroid gland, leading to impaired hormone synthesis. The thyroid may respond to excess iodine with a Wolff-Chaikoff effect, a phenomenon where iodine overload inhibits thyroid hormone synthesis, potentially leading to more severe hypothyroidism.
Secretion of Thyroid Hormones
Secretion of Thyroid Hormones*Colloid droplets taken up by follicle cells by endocytosis
*Lysosomes fuse with colloid droplets–Thyroglobulin degrades–Degradation products recycled
*Released T3 and T4 hormones diffuse into fenestrated capillaries surrounding the follicles
*In blood, hormones bind to plasma proteins–Mostly thyronine-binding protein (TBP)–Some prealbumin (TBPA) & albumin–T4 binds with ↑ affinity → ↑ half life (t½)
