week 4, lecture 2 Flashcards
what does the thyroid develop from in embryo?
Originates from the endodermal lining of the primitive pharynx
where does the thyroid develop at (embryo)
- The thyroid begins to develop as a pit at the base of the tongue in the midline (Foramen Cecum)
- Begins as a small endodermal thickening in the floor of the pharynx, near the base of the tongue.
- foramen cecum, between the 1st and 2nd pharyngeal pouches in the 3rd week
- Here is when the the thyroid diverticulum forms, which descends through the neck.
- The thyroid descends from the foramen cecum (at the tongue base) via the thyroglossal duct.
what week in embryo does the thyroid reach its final position in front of the trachea
7th week
what is the thyroid composed of
Thyroid develops into two lateral lobes connected by an isthmus.
what is the thyroglossal duct
- Temporary duct that connects the developing thyroid to the tongue.
- Normally, the duct disappears by the 10th week
- In some, the pyramidal lobe is an extension fo the duct
- but remnants of it can lead to thyroglossal duct cysts.
- 7% of the population has this. A Midline swelling can possibly be apparent
by the 7th week in embryo what happens
- the thyroid gland is in its final anatomical position.
- Anterior to the trachea and Below the larynx
what does the thyroid consist of
- Two lateral lobes * Isthmus
what does the thyroid look like
- Shaped kind of like a butterfly, the isthmus usually lies below the cricoid cartilage
▪ Right and left lobes, connected via the Isthmus
▪ In some individuals, a pyramidal lobe extends superiorly from the isthmus (remnant of the thyroglossal duct)
arterial supply for thyroid
- Superior thyroid artery (branch of external carotid artery). * Inferior thyroid artery (branch of subclavian artery).
venous drainage of thyroid
- Superior thyroid vein.
- Middle thyroid vein.
- Inferior thyroid vein
All drain into the SVC (superior vena cava) via the brachiocephalic trunk
what is a cricothyrotomy?
Cricothyrotomy is a “famous” urgent airway procedure
- Locate the junction of the cricoid and the thyroid cartilage
- Small incision provides quick and pretty save access to the trachea
- The thyroid is extraordinarily vascular – if one slices indiscriminately in this area, hemorrhages happen
what is the capsule of the thyroid
- The thyroid gland is enclosed by a thin fibrous capsule.
- This capsule serves both as a protective layer and as an anchor for the gland to nearby neck structures.
- The capsule is not just superficial—it sends septa (thin partitions) deep into the thyroid, dividing the gland into smaller lobules.
- This internal structure helps compartmentalize the tissue for efficient blood flow and hormone production.
- The capsule is also firmly attached to the cricoid cartilage and the upper part of the trachea
- The thyroid moves up and down when you swallow, a key clinical sign used during physical examination of the gland.
what is the thyroid made up of
thyroid follicles
The functional units responsible for hormone production.
A follicle is a spherical structure, typically surrounded by a single layer of cuboidal epithelial cells (known as follicular cells or thyrocytes).
what are thyroid follicles filled with
colloid (fluid) that contains pro hormone thyroglobulin
what are follicular cells responsible at synthesizing
synthesizing and secreting thyroid hormones thyroxine (T4) and triiodothyronine (T3) via enzymes
what is in the parafollicular area
Between the follicles, in the interstitial spaces, are clusters of parafollicular cells (also called C cells).
what are parafollicular cells responsible for
These cells are responsible for producing calcitonin, a hormone that helps regulate calcium levels by inhibiting bone resorption when calcium levels are high
what do parafollicular/ c cells produce? and why?
calcitonin
regulate calcium levels (inhibit bone resorption when calcium levels are high)
calcitonin is not directly involved in metabolic processes but plays a role in calcium homeostasis.
what happens to the follicular cells when they are inactive vs active
- Inactive: flat cells, lots of colloid
- Active: cells become cuboidal or columnar as they take up the colloid via “reabsorption lacunae”
- Fenestrated capillaries
what are the main ingredients to make thyroid homrone
tyrosine and iodine
what is produced in a high amount but less active and what is produced in low amounts but is more active ; t3 or t4
t4: * High amount is produced, but it is less active
t3: * Very little is produced, but it is VERY active
how can t4 be converted into t3
- Can be converted into T3 in the periphery by deiodination
(removal of iodine)
what is reverse t3
- Produced in the periphery; small amount; activity unclear
what are thyroid hormones the derivative of
tyrosine
- Thyroid hormones (T3 and T4) are derivatives of the amino acid tyrosine.
- Tyrosine is an aromatic amino acid that forms the backbone of the thyroid hormones.
amino acid to make thyroid hormones
tyrosine
what are thyroid hormones made of
The production of thyroid hormones involves the coupling of two tyrosine molecules that undergo a series of modifications, particularly iodination.
what is the structure of tyrosine? what are the carbon positions where it can get iodinated?
- Each tyrosine molecule has an aromatic ring structure with carbon atoms at positions 1 through 6.
- For thyroid hormone synthesis, iodination occurs specifically at the 3- and 5-carbon positions on the ring.
what is iodination
Iodination refers to the process where iodine atoms are added to these carbon positions.
what is monoiodotyrosine (MIT)
A tyrosine molecule with one iodine at the 3-carbon.
what is diiodotyrosine DIT
A tyrosine molecule with two iodines, at both the 3- and 5-carbons.
what is T3 made of (i.e. DIT or MIT)
Formed when one MIT combines with one DIT, resulting in a molecule with three iodine atoms.
what is T4 made of (i.e DIT or MIT)
Formed when two DIT molecules combine, creating a molecule with four iodine atoms.
t3 vs t4 for DIT and MIT
t3= dit and mit
t4 = 2 dit
where does the coupling process of adding mit and dit to make t3 and t4 happen
takes place within the colloid of the thyroid follicles.
what is thyroid hormone derived from
- Two tyrosine molecules “stuck” together with variable levels of iodination on the 3- and 5-carbon of aromatic ring
what are tyrosine initially part of
a larger protein known as thyroglobulin
what is thyroglobulin
- Thyroglobulin is a large glycoprotein that acts as a precursor and scaffold for thyroid hormone synthesis.
- It is a large protein, containing about 2750 amino acids, and is synthesized and secreted by follicular cells into the colloid of the thyroid follicles.
how many tyrosine residues in thyroglobulin; how many can be used
123
4-8
- Within the thyroglobulin protein, there are 123 tyrosine residues available.
- However, not all of these residues are used for hormone synthesis.
- Only 4-8 tyrosine residues within thyroglobulin are actually iodinated and incorporated into the final thyroid hormones (T3 and T4).
- These specific tyrosine residues are selectively iodinated, and the iodinated tyrosine pairs are linked together to form T3 and T4.
where is thyroglubin made and stored?
Synthesis and Storage: Thyroglobulin is produced in the follicular cells and secreted into the colloid, where the tyrosine residues undergo iodination and coupling to form hormone precursors.
why is thyroglobulin endocytose
Endocytosis and Proteolysis: When thyroid hormones are needed, the thyroglobulin is taken back into the follicular cells via endocytosis.
where is thyroglubin released itno
Release: Inside the follicular cells, enzymes cleave the thyroglobulin, releasing the active hormones (T3 and T4) into the bloodstream.
overview of formation and secretion of thyroid hormone
- Iodide absorption and transport
- Iodide uptake by the follicular cells + thyroglobulin synthesis (not “connected”)
- Transport of thyroglobulin and iodide into the follicle (not “connected”)
- Iodination of tyrosine residues on thyroglobulin
- Endocytosis of thyroglobulin (now with iodinated thyronine residues on it)
- Lysosomal destruction of endocytosed thyoroglobulin release of thyroid hormone into the cytosol
- Thyroid hormone enters the circulation and is carried to peripheral tissues via transport proteins
what symporter helps bring iodide from the diet into the follicular cell
a significant proportion of the iodide in the diet is absorbed into the follicular cell from the circulation by a very high-affinity sodium-iodide symporter
where is iodide mostly secreted to
- Iodide is mostly secreted into the urinary system, some into bile
how does iodide circulate
- As thyroid hormone is metabolized, iodide is liberated and circulates
where is iodine absorbed
small intestine
where is iodine stored/ used
Thyroid (for thyroid hormone production)
Up to 2 months supply Kidneys (excreted in urine)
Secondary locations: salivary glands, gastric mucosa, placenta, ciliary body of eye, choroid plexus, mammary glands (physiological role of iodine in these tissues is unclear)
how is iodine excreted
Liver metabolizes thyroid hormones and releases some iodine into bile attached to the metabolites (some is reabsorbed)
80% is excreted via kidneys
how is iodide absorbed and transported
- Dietary iodide is rapidly absorbed through the gastrointestinal (GI) tract into the bloodstream.
- Most dietary iodide comes from sources like iodized salt, seafood, and dairy products.
- Once in the bloodstream, iodide is transported to the thyroid gland, where it is actively concentrated for thyroid hormone synthesis.
how is iodide uptake by follicular cells
Na/I cotransporter (NIS)
sodium iodide symporter
where is the sodium iodide symporter located?
- Located on the basolateral membrane of the thyroid follicular cells (the side facing the blood).
- The NIS (also known as SLC5A5) is a specialized Na+/I− cotransporter responsible for actively transporting iodide from the blood into the follicular cells.
which way does the iodine and sodium go in the Na/I symporter (NIS)
- The NIS moves two Na+ ions and one iodide ion (I−) simultaneously into the cell.
where is iodide concentration highest (in blood or cell)? hint- active transport occurs
- Iodide transport by the NIS occurs against its electrochemical gradient, meaning iodide is moved into the cell even though its concentration inside the follicular cell is already higher than in the blood.
what energy is needed to actively transport iodide into the cell
- The energy for this process is provided by the sodium gradient, which is maintained by the Na+/K+ ATPasepump located on the basolateral membrane.
Sodium gradient:
* The Na+/K+ ATPase pumps sodium ions out of the follicular cell in exchange for potassium ions.
* This creates a low intracellular Na+ concentration, which drives the movement of Na+ into the cell along with iodide.
once iodide gets into the follicular cell how does it get into the lumen
Cl-/I- exchanger AKA pendrin
Once inside the follicular cell, iodide needs to be transported into the lumen of the thyroid follicle (colloid), where it will be used for hormone synthesis.
what is the purpose of pendrin
- Iodide is transported across the apical membrane (the side facing the follicular lumen) by the Cl−/I− exchanger, known as pendrin.
- Pendrin moves iodide (I−) into the follicle in exchange for chloride (Cl−) ions.
pendrin: Cl-/I- exchanger
- Pendrin is a protein located on the apical surface of the follicular cell, responsible for secreting iodide into the follicle lumen.
- Pendrin (SLC26A4) exchanges one chloride ion (Cl−) for one iodide ion (I−), allowing iodide to leave the cell and enter the colloid where it is used for thyroid hormone synthesis.
pendred syndrome (mutations in pendrin) symptoms
-goiter
-hearing loss
-Impaired iodide transport can lead to hypothyroidism or compensatory goiter, as the thyroid enlarges in an attempt to capture more iodide.
pendred syndrome
- Caused by mutations in the SLC26A4 gene, which encodes the pendrin protein.
where is thyroglobulin made? what groups does it contain? and how is it made into t3 and t4?
- Thyroglobulin (TG) is a glycoprotein synthesized by the follicular cells of the thyroid gland.
- It contains the tyrosyl groups (tyrosine residues) that will be iodinated to form thyroid hormones (T3 and T4).
- It contains 123 tyrosine residues, but only 4-8 of these will be used to form the thyroid hormones.
where is thyroglobulin synthesized and where is it packaged? how is it transported to then get exocytosed?
- TG is synthesized in the rough endoplasmic reticulum (RER) and packaged in the Golgi apparatus of the follicular cell.
- It is transported in secretory vesicles that carry it to the apical membrane, where it is exocytosed into the follicle lumen (colloid).
what is thyroid peroxidase? where is it located?
- Along with TG, the secretory vesicles also carry the enzyme thyroid peroxidase (TPO), which is an integral membrane protein.
- TPO is anchored in the apical membrane of the follicular cell, with its catalytic domain facing the follicle lumen (colloid), where iodination occurs.
what is the function of thyroid peroxidase?
turn iodide into iodine
- TPO catalyzes the oxidation of iodide (I−) into iodine (I*), which is a key step in thyroid hormone synthesis.
- The oxidized iodine forms a highly reactive iodine radical (I*), which is essential for attaching to tyrosine residues on thyroglobulin.
what turns iodide into iodine
thyroid peroxidase
what is DUOX2
membrane protein used to help thyroid peroxidase do the oxidation reaction
- The oxidation reaction carried out by TPO requires the activity of another apical membrane protein, known as DUOX2 (Dual Oxidase 2).
- DUOX2 generates hydrogen peroxide (H2O2), which is necessary for TPO to oxidize iodide into the iodine radical.
how are the iodinated tyrosines (DIT and MIT formed)
TPO gets iodide into iodine radical which can be added to tyrosines
Once the iodine radical is formed, it reacts with the tyrosine residues on thyroglobulin in the follicle lumen.
* This process is catalyzed by TPO and leads to the formation of iodinated tyrosines:
* Monoiodotyrosine (MIT): Tyrosine with one iodine attached. * Diiodotyrosine (DIT): Tyrosine with two iodines attached.
what DIT and MIT make T4 and T3
- TPO then facilitates the coupling of iodinated tyrosines:
- Two DIT molecules combine to form T4 (thyroxine).
- One MIT and one DIT combine to form T3 (triiodothyronine).
what stimulates iodinated thyroglobulin to get endocytosed
TSH
Endocytosis of Iodinated Thyroglobulin
* Thyroglobulin has been iodinated and contains some coupled MIT and DIT residues (forming T3 and T4) remains in the colloid until the thyroid is stimulated to release hormones.
Endocytosis:
* When stimulated by TSH (thyroid-stimulating hormone), the iodinated thyroglobulin is taken back into the follicular cell via endocytosis.
* This forms vesicles containing TG, which are transported into the cell for further processing.
*
what do the iodinate thryoglubin fuse with to break it down and release T3 and T4
lysosomes
what is lysosomal hydrolysis of iodinated thyroglobulin for?
release t3 and t4 into cytosol
- Once inside the follicular cell, the vesicles containing iodinated thyroglobulin fuse with lysosomes.
- Lysosomal enzymes hydrolyze the thyroglobulin, breaking it down and releasing T3 and T4 into the cytosol.
what happens to t3 and t4 when lysosomes hydrolyze them from thryroglublin? what happens to the unmodified part of the TG?
- T3 and T4 are freed from the thyroglobulin backbone
- While unmodified tyrosyl residues (MIT and DIT) are deiodinated and recycled within the follicular cell.
how does t3 and t4 get into blood
unknown… but in blood bind thyroxine-binding globulin, transthyretin and albumin to get to periphery
After being released from thyroglobulin, T3 and T4 need to leave the follicular cell and enter the bloodstream to exert their effects on target tissues.
Transport Mechanism:
* The exact mechanism of how T3 and T4 leave the cell is not fully understood.
* In the bloodstream, T3 and T4 bind to transport proteins like thyroxine-binding globulin (TBG), transthyretin, and albumin to be carried to peripheral tissues.
what do t3 and t4 bind to (3 things) to get carried to target tissue in bloodstream
thyroxine-binding globulin (TBG), transthyretin, and albumin
effects of increased secretion of TSH from anterior pituitary
▪ Increase the activity of the sodium-iodide symporter
▪ Increases the synthesis of thyroglobulin
▪ Increases the activity of thyroid peroxidase
▪ Increases endocytosis of “iodinated” thyroglobulin
▪ Increases the proteolysis of thyroglobulin
▪ Stimulates the growth of the follicular cells and gland in general
what are the active vs inactive forms of thyroid hromones
inactive- mit and dit
active- t3 and t4
Inactive Forms:
* MIT and DIT represent half of the iodinated tyrosines, are not secreted, and are recycled within the thyroid cells.
Active Forms:
* T3 and T4 constitute the other half, with T4 being the predominant hormone released into the bloodstream.
t3 and t4 function vs reverse t3
- T3 and T4 regulate critical physiological functions, whereas rT3 serves as a regulatory metabolite in certain conditions.
are t3 and t4 hydrophilic or hydrophobic
hydrophobic
- T3 (triiodothyronine) and T4 (thyroxine) are hydrophobic molecules due to their structural composition
- This limits their solubility in aqueous environments like blood plasma.
- Only a very small fraction of these hormones exists in their free (unbound) form within the bloodstream.
how do t3 and t4 travel in blood
99% are bound to plasma proteins
- Approximately 99.98% of T4 and 99.8% of T3 in circulation are bound to plasma proteins.
- This high degree of binding protects the hormones from rapid metabolism and excretion, prolonging their half-lives.
what’s more tightly bound, t3 or t4
t4 is tighter
- T3 is less tightly bound to carriers compared to T4.
- This results in a higher proportion of free T3 available to tissues for immediate action.
longer vs shorter half life of t3 and t4
t4 longer, t3 shorter
- T4 has a longer half-life
- T3 has a shorter half-life
- The shorter half-life of T3 makes it more readily available for tissues that require immediate responses, even though it circulates at lower concentrations.
t3 is also less tightly bound
is t3 or t4 more available
t3
- The free (unbound) fractions of T3 and T4 are biologically active and capable of entering target cells to exert their effects
. - The relatively higher availability of free T3 allows it to more quickly influence metabolic processes in various tissues.
what is the primary carrier for t3 and t4
albumin; is the most abundant protein in the blood
what is the affinity albumin has for t3 and t4
low
While it has a lower affinity for thyroid hormones compared to other carriers, its abundance means it plays a significant role in transporting these hormones.
transthyretin; affinity for t3 and t4
- Transthyretin is another important transport protein that binds both T3 and T4.
- It has a moderate affinity for these hormones and helps in stabilizing their levels in circulation
what transport protein has the highest affinity for t4
thyroid binding globulin (TBG)
what does thyroid binding globulin bind for with high affinity
t4
- TBG has the highest affinity for T4 among all transport proteins, meaning it binds T4 more tightly than T3.
- As a result, TBG is responsible for carrying the majority of T4 in circulation, which helps maintain its stable concentration over time.
how do thyroid hormones enter cells
diffusion or transportes
- While some studies suggest that thyroid hormones may enter cells via simple diffusion due to their lipophilic nature
- it is increasingly recognized that specific transporters may facilitate their uptake but still being characterized
what happens when t4 enters the target tissues
deoiodination
a process that removes iodine atoms to convert T4 into its more active form, T3, or its inactive form, rT3.
what does t4 become when it gets deiodinated
t3
what are the enzymes for deiodination
- Deiodinase type 1 (D1) * Deiodinase type 2 (D2).
and also
deiodinase type 3 (slightly different role)
what does deiodinase type 1 do
convert t4 to t3
can also produce small amount of reverse t3
where is deiodinase type 1 found
- D1 is predominantly found in the liver, kidneys, thyroid, and pituitary gland.
what is the significance of deiodinase type 1 (D1)
- By generating T3, D1 helps maintain the physiological effects of thyroid hormones in tissues where T4 levels are higher.
- The presence of D1 in the liver is particularly important for the regulation of systemic thyroid hormone levels.
where is deiodinaase type 2 found
- D2 is primarily found in the brain, pituitary gland, and brown adipose tissue.
deiodinase type 1 vs 2 vs 3 location
- D1 is predominantly found in the liver, kidneys, thyroid, and pituitary gland.
- D2 is primarily found in the brain, pituitary gland, and brown adipose tissue.
Deiodinase Type 3 (D3) is predominantly found in the brain and reproductive tissues.
deiodinase type 2 role
convert t4 to t3
role of deiodinase type 2
D2 plays a crucial role in local T3 production in the brain, which is important for regulating metabolism and overall brain function.
what adaptive mechanism does deiodinase type 2 have
- The expression of D2 can be influenced by various physiological conditions (e.g., caloric intake, temperature), allowing the body to adapt thyroid hormone availability to its metabolic needs.
where is deiodianse type 3 found
Deiodinase Type 3 (D3) is predominantly found in the brain and reproductive tissues.
what is deiodianse type 3 role
convert t4 into reverse t3 and inactivate t3
deiodinase type 1 2 and 3 what do they convert
3 converts t4 tp reverse t3 and also inactivate t3
1 and 2 convert t4 to t3
importance of deioidanse type 3 and producing reverse t3
- D3 facilitates the removal of iodine from T4, leading to the formation of rT3, which is biologically inactive.
- This function is particularly important in contexts where reduced metabolic activity is needed, such as during stress or illness.
what cofactor do the deiodinases (D1, D2, D3) alll need for their enzymatic activity
selenium
why does selenium as a cofactor for the deiodinases (D1, D2, D3)
due to the presence of selenocysteine residues in their active sites, which are essential for the deiodination process.
what residues do thyroid hormones have that need selenium
selenocysteine resideus
selenium importance
- Selenium is a vital trace mineral that plays a crucial role in thyroid hormone metabolism and overall endocrine health.
- A deficiency in selenium can impair the function of deiodinases, leading to altered thyroid hormone levels and potentially contributing to conditions such as hypothyroidism.
how is reverse t3 formed? is it active or inactive?
- rT3 is formed during the deiodination of T4, typically when one iodine atom is removed from the outer ring of T4.
- Although rT3 is considered an inactive metabolite, its levels can rise in certain conditions, such as fasting or illness, serving as a mechanism to downregulate metabolism.
what is the physiological role of reverse t3? what does it do to reduce t3
- rT3 competes with T3 for receptor binding but does not activate the thyroid hormone receptors, thus effectively reducing metabolic activity during times of stress or caloric restriction.
what are deiodinases influenced by
▪ Age (less T3 made during fetal life)
▪ Drugs
▪ Selenium deficiency
▪ Illness (burns, trauma, advanced cancer, cirrhosis, chronic kidney disease, MI, febrile state)
▪ Diet
* Fasting: reduces T3 by 50% in 3-7 days (rT3 is increased)
* Overfeeding: increases T3 and reduced rT3
impact of fasting vs overfeeding on t3 and rt3
- Fasting: reduces T3 by 50% in 3-7 days (rT3 is increased)
- Overfeeding: increases T3 and reduced rT3
what has a higher affinity for thyroid hormone receptor in the cell; t3 or t4
t4 has lower affinity than t3
what type of receptor is TSH recepetors
g-protein coupled receptor
what activates the GPCR of the TSH receptor
phospholipase C
what do TSH receptors GCPR increase?
Increases iodide binding
Increases synthesis of T4 and T3
Increases secretion of thyroglobulin into colloid
Increases blood flow to thyroid
what does chronic high stimulation of the TSH receptors do
hypertrophy or goiter
where is TSH secreted from and in response to what
Thyroid Stimulating Hormone (TSH) is secreted by the anterior pituitary gland in response to Thyrotropin-Releasing Hormone (TRH) from the hypothalamus.
where is TRH come from and what does it stimulate
hypothalamus and stimulate TSH in anterior pituitary
where does TSH from anterior pituitary bind to and what does it cause secretion of
- TSH binds to receptors on the thyroid follicular cells, stimulating the synthesis and secretion of thyroxine (T4).
- T4 is the primary hormone produced by the thyroid and is largely responsible for regulating metabolism throughout the body.
once t4 is secreted into the bloodstream; what are the 2 forms that it can exist as
free t4 or bound t4
what is free t4
The unbound form, which is biologically active and able to enter cells and exert effects.
what is bound t4
The majority of T4 binds to plasma proteins, such as thyroid- binding globulin (TBG), transthyretin, and albumin. This binding helps regulate the availability of T4 and provides a reservoir for hormone storage.
what is the majority of t4 in the bloodstream; bound or unbound
bound
to plasma proteins, such as thyroid- binding globulin (TBG), transthyretin, and albumin
equilibrium between free t4 and bound t4
- There is a dynamic equilibrium between free T4 and bound T4.
- Changes in protein levels (such as during pregnancy or illness) can alter the amount of free T4 available, affecting physiological responses.
how does free t4 help regulation TSH
negative feedback
- The levels of free T4 in the bloodstream are critical for regulating TSH secretion
- When free T4 levels rise, they exert a negative feedback effect on the anterior pituitary gland.
- This feedback mechanism inhibits the secretion of TSH, thus reducing stimulation of the thyroid gland and decreasing T4 production.
- This ensures that hormone levels remain within a normal physiological range.
how does t3 regulate TSH secretion
negative feedback
- T3, like free T4, also has a negative feedback effect on the pituitary gland, further inhibiting TSH secretion.
- This feedback mechanism is vital for maintaining the delicate balance of thyroid hormones and ensuring that metabolic processes function optimally.
how is TSH similar to LH, FSH and hCG
Alpha subunit is identical, beta subunit is unique (glycoprotein tropic hormone)
what is the half life of TSH, where is it excreted
60 mins and excreted in kidneysh
how is TSH secreted? when is its peak?
peak at midnight
- Pulsatile secretion, pulses increase in amplitude, frequency at night (peaks at midnight) Degraded and excreted mostly via kidneys
Pulsatile secretion with rise at 9pm, peak at midnight and decline after
t3 and t4 effects on the heart
chronotropic and ionotropic
increased number of beta andrengeric receptors
enhanced response to circulating catecholamines
increased proportion of alpha myosin heavy chain (with higher ATPase activity)
t3 and t4 effects on adipose tissue
catabolic
stimulated lipolysis
t3 and t4 effects on muscle
catabolic
increased protein breakdown
t3 and t4 effects on bone
developmental
promote normal growth and skeletal devleopment
t3 and t4 effects on the nervous system
devlopmental
promote normal Brian devleopment
t3 and t4 effects on the gut
metabolic
increased rate of carbohydrate absorption
t3 and t4 effects on lipoprotein
metbaolic
formation of LDL receptors
t3 and t4 effects on calories and metabolism
calorigenic
stimulated oxygen consumption by metabolically active tissues
increased metabolic rate
t3 activities
increase or decrease BMR
- Increase basal metabolic rate
- Greatly aid in normal growth and development
hyperthyroid and hypothryoid- decrease or increase BMR
hyper-increase
hypo-decrease
hyperthyroid and hypothryoid effect on carb metabolism
GNG
glycogenolysis
serum glucose
hyper
-increase GNG and glycogenolysis
-serum glucose norma;
hypo
-decrease GNG and glycogenolysis
-serum glucose normal
hyperthyroid and hypothryoid
protein metabolism impact
hyper- increase synthesis and proteolysis
-muscle wasting present
hypo
-decrease synthesis and proteolysis
hyperthyroid and hypothryoid impact on lipid metabolism
lipogeneissi, lipolysis and cholestero
hyper
-decrease lipogenesis and cholesterol
-inceased lipolysis
hypo
-increased lipogenesis and cholesterol
-decreased lipolysis
hyperthyroid and hypothryoid impact on thermogeneiss
hyper- increased
hypo- decreawsed
hyperthyroid and hypothryoid impact on ANS (catecholamines)
hyper- increased expression of catecholamine recepeotrs
hypo- globally reduced catecholamine signalling
calorigenic (heat-producing actions of t3 and t4
- Increase energy (oxygen) consumption in almost all tissues except for the brain (including pituitary) and adult reproductive organs
what are calorigenic effects
▪ Increased fatty acid mobilization
▪ Increased activity of the sodium/potassium ATP-ase… everywhere
▪ Increased cardiac output & sympathetic nervous system effectiveness
▪ Activation of uncoupling protein in brown fat and perhaps other cells more prominent effect in young children
calorigenic action
Increase O2 consumption in almost all tissues
Increase Na+ K+ ATPase activity
Increase fatty acid metabolism
Increase metabolic rate
–May result in weight loss if intake of nutrients doesn’t match
–Small amounts of T3 stimulate growth, but high amounts promote catabolism
Increase requirement for all vitamins
–>Thyroid hormones are also needed for liver’s metabolism of carotene into vitamin A
Other general effects:
Facilitates normal menstrual cycle Allows for milk secretion
Support normal skin structure
cardiovascular impacts of t4 and t3
▪ Vasodilation –>decreased peripheral resistance –>modestly increased sodium and water reabsorption (increased blood volume)
▪ As mentioned, increased effectiveness of SNS on the heart –>
neurological impacts of t3 and t4
▪ very, very important in early neurological development in the fetus and infant
* CNS,basalganglia,specialsenses(cochlea)
▪ Increases arousal and activation of reticular activating system, overall neuronal “excitability” (i.e. hypothyroidism –>
t4 and t3 on carb metabolism
▪ Increased absorption of carbohydrates from GI, increased gluconeogenesis, increased glycogenolysis
- However, blood glucose tends to remain normal, likely due to increased consumption
impact of t3 and t4 on muscle growth, skeletal growth, cholesterol
- Lower circulating plasma cholesterol
▪increased synthesis of LDL receptors - Muscle growth
▪ Hard to characterize–seems to both aid development but also lead to
increased protein turnover (hyperthyroidism muscle weakness) - Skeletal growth
▪ Key for normal growth in childhood and skeletal maturity ▪ Facilitates function of growth hormone - Also has impacts on skin appearance/structure, milk secretion, and the normal menstrual cycle
impact of congenital hypothryoid on normal delvoepment
This is a graph of developmental age— that is, the age that the child appears based on height, bone radiograph, and mental function—versus chronological age.
For a euthyroid child, the relationship is the straight line in red
The three green curves are growth curves for a child with thyroid hormone deficiency
* At age 4.5 years thyroid hormone replacement therapy was initiated. Notice the “catching up” of bone and height parameters, but the lag in cognitive parameters
Other thyroxine, TSH, and TBG notables
- Increased metabolic rate due to hyperthyroidism –>increased requirements for all vitamins
- TSH release is induced by cold (in infants)
- TSH release is inhibited by cortisol and stress
▪ Impacts on pituitary and hypothalamus - TBG can be increased with elevations in estrogen (and during pregnancy) and with some medications
▪ Increases “store” of bound thyroxine, no impact on free levels
- TBG can be decreased by glucocorticoids, androgens, and other medications
▪ Still no impact on free levels of hormone
