Thyroid Flashcards
Shape and location of thyroid
Butterfly shape and located below larynx
Blood supply of thyroid
large blood supply, like all endocrine organs
Which kind of nerve innervate thyroid gland?
Innervated by sympathetic nerves
What is the functional unit of thyroid gland
thyroid follicles
What are thyroid follicles made of?
consisting of a single layer of epithelial cells surrounding a lumen that contains colloid
WhaT is colloid made of
contains the prohormone thyroglobulin
What are parafollicular cells? What is their role?
Parafollicular cells, also called C cells, are neuroendocrine cells in the thyroid.
The primary function of these cells is to secrete calcitonin. T
hey are located adjacent to the thyroid follicles and reside in the connective tissue.
What is the function of thyroid hormone?
to secrete the quantity of thyroid hormone to meet the demand of peripheral tissues
each follicle is marked by a __
each follicle is marked by a basement membrane
Difference between inactive and active epithelium lining the folicular cells?
inactive epithelial cells are cuboid active-> columnar
What regulates the thyroid hormone release? How?
The blood flow regulates the thyroid hormones release by affecting the the delivery of TSH, iodine and nutrients
Where are cilia found in thyroid follicular cells
present towards the epical end of the cells, towards the lumen where colloid is
__nerves control the blood flow through the gland
What does this control in effect?
Postganglionic sympathetic nerves control the blood flow through the gland
thus determines iodine and TSH supply, determining T3 and T4 synthesis
Overactive vs inderactive throid gland cells
What are the biologically active forms of thyroid hormones? WHat are the inactive forms?
T4 and T3- active
inactive: rT3 and T2
Wher are rT3 and T2 formed?
in the periheral tissues
Which percursors of thyroid hormones do not leave the cells?
Monoidootyrosine
Diiodotyrosine
Chemcial names of T4 and T3? How are they assigned?
the one ring closest to COOH amino terminal is numbered witout primes
the furthest ring is given a prime
What kind of receptor is used by TSH? Which pathways?
GPCR receptor- cAMP or IP3/DAG
How does iodine get into our bodies?
- Epical side of intestinal cells have cilia
- iodine has to come from the diet and enter the epithelial cells
- PDS is present on the epical side; a transporter of iodine that moves it into the collide
- iodine is charged- is brought into the blood by a transporter NIS (sodium iodide symporter) -co-transporter; ions are transporter in the same direction
- iodine levels in the blood are much lower than the levels in epithelial cells or colloid-> iodine is transported by active transport against the gradient
- Sodium is brought down the gradient, iodine is brought against the gradient
- Sodium-potassiumATPase- maintains sodium gradient across cell membrane; present in all cell; results in less sodium in the cell compared to the outside
Describe iodine synthesis pathway
1) Iodine, as it is charged, is transported from plasma into follicular cells across the basal lateral membrane via Na-I symporter (NIS); uses electro-chemical gradient to drive the transport of 1 iodine ion and 2 Na in the same direction
2) Na is then transported out of the cell back to the blood via K-Na ATPase;
via the iodine ion is transported across the epical membrane into the colloid space via PDS that is present on the epical side; a transporter of iodine that moves it into the collide
Thyroglobulin is protein that comes to colloid where now thyroglobulin has to be iodinated
iodination requires hydrogen peroxide
Dual oxidase (DUOX) creates H2O2-> thyroglobulin is now iodinated
Iodinated thyroglobulin can have mono or diiodo tyrosine; It also has T3 and T4;
Iodinated thryglobulin is internalized => mono or diiodo tyrosine are cleaved off and are deiodinated; this iodine that comes from mono and diiodo tyrsines are recyceld
they come back to the pool of iodine in colloid; tyrosine gets recycled for the synthesis of thyroglobulin
T3 and T4 are now created and are transported out but we don’t know how
Iodination of tyrosine molecules causes thyroid peroxidase to conjugate neighbouring tyrosine residues, forming either T3, T4or rT3
TG protein which is now iodinated will be endocytosed
Lysosomes containing proteases will fuse with TG protein containing versicle and cleave peptide bonds where T4. T3 or rT3 are located
Once cleaved T4 and T3 are transported out of the cell
What is “trapping” in the process of T4/T3 synthesis
active transport of iodine into the thyroid cell via Na-I symporter
lots of iodine is required- at least 3 iodines per hormone-> iodine is trapped
What is “organifaction” in the process of T4/T3 synthesis
oxidation of iodide and iodination of tyrosyl residues in thyroglobulin
iodine cannot stay in its organic form as it would contribute to the charge
becomes organic as it is present in an organic molecule
What is known as “coupling” in the process fo T4/T3 production
linking pairs of iodotyrosines in thyroglobulin to form T3 and T4
WHat is proteolysed in the process fo T4/T3 production
proteolysis of TG to release T3 and T4
WHat is deiodinated in the process fo T4/T3 production
5) deiodination of iodotyrosines in thyroid cell and recycling of I-
6) intrathyroidal 5’-deiodination of T4 to T3
What are the 3 components required for thryoid gland synthesis?
thyroid hormone synthesis requires that NIS (Na+/I- symporter), TG (thyroglobulin), TPO (thyroid peroxidase)
Long nad short inhibiton loops of T4/T3 synthesis
WHat is the major source of iodine in our diets?
salt
How do iodine reuqirements change throughout life?
Highest durign pregancy, lower in adults, lowest in children
NIS (Na/I Symporter) stimulated by _
NIS (Na/I Symporter) stimulated by TSH
Is idoine transported down or against the concentration gradient when it is transported from blood plasma into cytoplasm?
Transport of iodine against a steep concentration gradient
- Iodine concentration in the blood plasma is extremely low; 30-40- fold difference between ECF and cytoplasm
What can block uptake of iodine?
how can this be used in hyperthyrodism?
Anions (such as ClO4-) block uptake of iodine;
perchlorate ( a chemical compound containing the perchlorate ion, ClO4-) can be used to block hyperthyroidism (also environmental inhibitor of thyroid)
What is NIS stimulated by?
NIS (Na/I Symporter) stimulated by TSH
Na+ gradient used by NIS is maintained by t__
Na+ gradient used by NIS is maintained by the ATP driven Na+/K+ pump
How are radioractive isotopes and Thyroid gland connected?
Radioactive iodine (oral I131) can be used to destroy thyroid tissue (in case of cancer or hyperthyroidism)
Bromide (Br-) and nitrite (NO2-) in the diet and iodine connection
Bromide (Br-) and nitrite (NO2-) are competitive inhibitors. Present in the diet. Causes apparent iodine deficiency in some areas of the world
sodium interacts with hallogens- Iodine, chloride, bromide, nitrates
these are salts of sodium
anions can compete with iodine for transport as its the charge that dictates the uptake
if these halogens are consumed-> iodine deficiency
What is Thyroshield?
ThyroShield Potassium Iodide- potassium iodide supplies a lot of iodide that can compete with radioactive iodide
Describe the structure of Thyroglobulin (Tg)
Large glycoprotein
- Dimer
- Contains about 140 tyrosines
How is Thyroglobulin and TSH connected?
TSH stimulates transcription/translation of TG in the follicular cells of the thyroid.
What happens to thyroglobulin in the Golgi?
Extensively glycosylated in the Golgi
Packaged into vesicles, exocytosed into the lumen of the follicle into the colloid
Tg is _% carbohydrate by weight
Tg is 10% carbohydrate by weight
Describe how iodination of Tg occurs
What is it also known as
Also known as organification
- Carried out by thyroperoxidase (TPO)
- Packaged in an inactive form together with thyroglobulin (Tg) into vesicles in the Golgi
- Activated at the apical membrane by co-factors
- also requires dualoxidase that creates H2O2 for incorporation of iodine into TG protein
What is the targt of Drugs inhibiting iodination?
Give an example of such drugs
Thyroperoxidase is the target for many drugs to reduce thyroid hormone production e.g. thiocarbamide inhibitors
inhibition of TG iodination-> less thyroid hormone production
What else, apart form drugs, can result in thyroid hormone production inhibition?
Several inhibiting compounds (goitrogens) are present in food (e.g. milk from cows fed certain plants, brassicae).
Block of iodination results in increased TSH production, resulting eventually in __ and __
Block of iodination results in increased TSH production, resulting eventually in hyperplasia and goiter
Which tyrosine become iodinated in the process of thyroid hormone production?
Only the tyrosines on the surface of the Tg become iodinated (about 1/3rd), only the ones on the periphery
WHat is the consequence of tyrosine iodination on Tg?
Causes structural change which leads to the formation of Triiodothyronine (T3) and thyroxine (T4) within the structure of thyroglobulin
__ catalyzes coupling.
TPO catalyzes coupling.
__ + __ -> T3
__ + __ -> T4
MIT + DIT -> T3
DIT + DIT -> T4
__ +__-> tyronine
happens on __
tyrosine ring + tyrosine ring-> tyronine
happens on thyroglobulin
__ reaction occurs simultaneously with the __ reaction.
__ may be broken during reaction
Coupling reaction occurs simultaneously with the iodination reaction.
Peptide may be broken during reaction
How many T3/T4 homrones can be formed within each Tg molecule?
Maximum of four T3 and/or T4 hormones within each Tg molecule are formed.
Describ the kinetics of thyroid hormone production
The kinetics is such that it keeps the level of T3 (the active form of the thyroid hormones) steady despite fluctuations in the dietary intake of iodine.
How is the rate of thyroid hormone production determined>
the occurrence of this process is determined by the requirement of T3 which in turn is regulated by TSH
Whered does the conversion of T4 to T3 coccur?
conversion of T4 to T3 coccurs in thyroid epithelial cells
What happens to Tg after it has been released into the colloid (follicle lumen)?
It has to be incorporated into the cell such that T3 and T4 get proteased and released
this happens via endocytosis which requires cilia - they form pseudopodocytes
once it is inside, this vesicle containing TG is lyzed by peptidases in lyzozymes
this enzymes cleave off tyrosines with iodines (MIT and DIT) and they cleave of T3 and T4
DIM and MIT are deiodinated by deiodinase, iodine goes back to colloid through buffer system; tyrosine goes to AA pool
T3 and T4 are transported out
How are T4/T3 transported out of the cell?
They are lipophilic-> diffuse out
Where are inactive thyroid horomones found?
Some are found in the serum
What is sick euthyroid syndrome
High levels of r-T3 in conjunction with low levels of T3 (“sick euthyroid syndrome” i.e. thyroid normal function but hypothyroidic as a metabolic adaption to some other condition e.g. anorexia, cancer)
What produces most of r-T3?
most of r-T3 is produced by peripheral tissues
How are thryroid hormones found in the circulation?
Lipophilic therefore bound to carrier proteins synthesized in the liver (99%)
Name thyroid hormone carrier proteins
– Thyroxine binding globulin(TBG)
– Transthyretin (thyroxine-binding prealbumin i.e. TBPA) - specific for T3 and T4
– Albumin
Effect of drugs on binding proteins and T3/T4 levels
examples
side effects
Some drugs compete with binding to the carrier protein and therefore elevate free T4 and T3
– Examples are some drugs for treating epilepsy and inflammation
→ Hyperthyroidism as a side effect
Half lives of T3 and T4 vs rT3
Half-life 1-3 days for T3 and 5-7 days for T4
- rT3 is cleared rapidly with a half-life of 5h
T3 vs T4 activity
T3 is 2-10 times more active than T4
T3 vs T4 levels in the circulation and their importance
- Total T3 is only about 2% of T4. However, stronger binding of T4 makes that the free concentration of T3 is about 30% of that of free T4
- Overall serum T3 and T4 are equally important (not counting tissue specific conversion)
importance of free thyroid hormones
Cells can only take up the free thyroid hormones, but not the carrier proteins → Free hormone concentration is important (only the free thyroid hormones are biologically active)
What determines the levels of free thyroid hormones?
The level of binding proteins determines the free hormone concentration
Consequence of high binding protein levels
What are the conditions associated with high thyroid hormone levels?
Binding protein high → More total hormone required to maintain free hormone level
- Pregnancy, oral contraceptives
Consequence of low binding protein levels
What are the conditions associated with low thyroid hormone levels?
Binding protein low → Less total hormone required to maintain free hormone level
- Starvation, liver disease
Tg vs thryoid binding protein site of production
thyroglobulin is made in thyroid glands; needed for thyroid gland produciton
thyroid binding globulin is made in the liver
Types of deiodinases, their location and function
Where is type 3 Deiodinase mostly expressed
mostly in peripheral tissues
What is the speicality of protein makeeup of Deiodinases?
All three deiodinases contain selenium in the form of the rare amino acid selenocysteine, the 21st amino acid (codon UGA). Only 25 selenocysteine containing proteins have so far been identified, 11 in thyrocytes
Basic organization of the Selenodeiodinases
seleno containing enzymes
Extracellular domain: NH2
Intracellular domain: COOH
Exists as a Dimer
Transmembrane enzyme
Deiodinases: Physiological Importance (3)
- permit local tissue and cell modulation of thyroid hormone
- help animal to adapt to changes including iodine deficiency or chronic illness e,g, D3 increases during hyperthyroidism and decreases during hypothyroidism
- regulate thyroid actions during early development
How’s most of T4 metabolized?
about 80 % of T4 is metabolized by deiodination (35 % to T3 (type 1,2) and 45 % to rT3 (type 3))
rest inactivated by liver by glucuronidation and biliary secretion
Describe thyroid hormone storage
- how big is it?
- Function?
The thyroid is unique by virtue of the large store of hormone even though it is lipid soluble ; The stored amount is enough to maintain a euthyroid state for at least 50 days.
Function: the reservoir provides prolonged protection in case synthesis ceases.
only a small amount of produced T3 and T4 get released to the circulation
if there’s something that effects the synthesis of thyroid hormones, such as lack of TSH, the effect of this will not be expressed for a long period of time-> survival in iodine deficient conditions
What is a con of such a large store of thyroid hormone?
negative side of storages:
- if all the stored amounts are released in response to a stimuli-> thyroid storm
What are the functions of thyroid hormone?
1) growth and development
2) Maintenance of basal metablic rate
Effect of receptor activation by T3/T4
How does the effect differ between T3 and T4?
The receptors activated by T3 and T4 modulate gene transcription (T3>T4)
What provides tissue specificiyt of response to thyroid hormones?
Interaction with other transcription factors provides tissue specificity
T3 and T4 are transcription factors
What kind of receptor is used by thryoid hormones?
In which form does it act?
Lipohilic-> nuclear receptor
ligand dependent transcription factor
Acts as monomer, homodimer or heterodimers
Effects of injection of T3 on thyroidectomized rats
Where do these changes occur
These changes occur in the liver
What is the effect of T3/T4 receptor binding on transcription?
may activate or inactivate transcription (Example: Activation of GH transcription, inactivation of TSH transcription
What is the Most common heterodimer partner of thyroid hormone receptor?
RXR
What are the genes that encode T3/T4 receptors?
THRA (NR1A1)- thyroid hormone alpha
and THRB (NR1A2)- thyroid hormone beta
Which class of nuclear receptors does thyroid horomone receptor belong to?
Where are they found?
thyroid hormones belong to the second family of nuclear receptors (NR)-> NR2
`Found in the nucleus, but some are also found in the mitochondria
How many receptor isoforms does each gene of thryoid nuclear receptor give rise to?
How?
How many possible types of receptors are there overall?
Each gives rise to two receptor isoforms by alternative splicing
thus there are 4 possible receptors
WHat modulates the effect of T3 and T4 on different tissues?
Tissue specific expression of these receptors modulates the effect of T3 and T4 on different tissues
How do thyroid hormones eneter the cell?
Ligand entry by passive diffusion, but in certain cells it may be aided by special transport systems like MCT8 or MCT10
What happens if there is too much of T3? Why?
rT3 is formed and readily cleared.
local regulation by cells, to reduce the effect of T3
Where is THRA gene found in choromosome?
Which receptors does it code for?
Describe those receptors
THRA gene is found on chromosome 17
Codes for a1 and a2 receptors
a1-> Widely distributed
a2-> Acts as an inhibitor (binds to TRE sequence but not ligand → transcriptional
repression); increased a2 receptor expression-> decreased thyroid hormone signalling
Where is THRB gene found in choromosome?
Which receptors does it code for?
Describe those receptors
Chormosome 3
β1-receptor and β2-receptor
β1-receptor-> widely distibuted
β2-receptor-> Anterior pituitary and specific brain regions
Mechanism of action
nucleus vs mitochondria
Nucleus:
TF is vound to HRE
- When not activated by the ligand, most of the time it is associated with co-repressor such as NCor (nuclear co-repressor) or SMAR (silencing mediators of RXR)
- the presence of co-repressor blocks the formation of pre-initiation complex -> no gene expression
When ligand (T3 or T4) binds-\> co-repressors are released and co-activators are recruited activators allows pre-initiation to be formed-\> transcription
Mitochondria
- One of the target genes of thyroid receptors is a transcription factor that is functional in the mitochondria
- This TF is expressed in the nucleus, goes into the cytoplasm, gets translated into a protein
- That protein is transported into mitochondria where it acts as a mitochondria-specific TF
- Thyroid hormones will act as transcriptional regulators
- Usually, the isoforms of nuclear co-activators and co-repressors that are present in the mitochondria are truncated proteins
- mitochondrial genes regulated by thyroid hormones are mostly involved in mitochondrial function in terms of TSA cycle, steroidogenesis and oxidative-phosphorylation
- Cytochrome C is involved in electron-transport chain/oxidative phosphorylation -activated by T2, which is diiodotyronine (not tyrosine!!! two benzine rings)
- T2 is inactive in terms of transcriptional activity as they cannot bind to classical NR
- T3 can activate UCP1- uncoupling protein/thermogenin- highly expressed in brown adipose tissue
- T3 interacts with complex of proteins, without depending on thyroid receptors and can activate UCP1
- thus thyroid hormones are important in general metabolism
- T2 binds to cytochrome c to increase oxidative phosphorylation
- T3 binds to uncoupling proteins to increase heat production
THRs to increase mitochondrial transcriptio
Thus T3 and T4 can signal via:
- gene activation in the nucleus
- gene activation in the mitochondria
- interaction with a membrane protein
Non-genomic function of thyroid hormones
Non-genomic function: ligand doesn’t activate smth in the nucleus
Sites of non-genomic action are localized to the plasma membrane, cytoplasm, cytoskeleton and sub-cellular organelles.
typically they need a membrane receptor : integrins are present in the plasma membrane and they connect the cytoskeleton with the extracellular matrix
Integrins are proteins that function mechanically, by attaching the cell cytoskeleton to the extracellular matrix (ECM), and biochemically, by sensing whether adhesion has occurred. The integrin family of proteins consists of alpha and beta subtypes, which form transmembrane heterodimers.
alphaVBeta3 is one of the proteins in that family, it is an integrin-> is known to be bound by T4
Intergrins usually tend to interact with nearby kinases and lead to activation of MAPK kinase pathway
- MAPK kinase results in various signalling pathways, typically activating other transcription factors
- ERK1 binds the genome
- Whenever there’s a MAPK kinase, there’s not only cytoplasmic activation of various proteins and cytsokeleton. but also transcriptional activation
T3 diffuses acros the membrane, instead of usign integrins-> results in MAPK pathway or PKC-> Na/H anitporter activation or Amino acid transporter activation
Physiological effects of thyroid hormone
Calorigenic action of Thyroid Hormones
T3 vs T4
v Increase of O2 consumption and heat production in metabolically active tissues
v Exceptions are adult brain, testes, uterus, lymph nodes, spleen and anterior pituitary (pituitary → feedback inhibition by T4)
v Some calorigenic effects are due to fatty acid mobilization and increase of Na+/K+ ATPase Activity
T3 and T4 increase oxygen consumption, especially in metabolically active tissues
in pituitary, T3 and T4 are mostly involved in negative regulation of TSH expression, not in the metabolism
Kinetics of Calorigenic action of Thyroid Hormones
Single dose of T4 → Measurable effect in several hours, lasts for 6 days or more
Effects Secondary to Calorigenesis
vIncreased nitrogen excretion (protein turnover increases leading to decreased skeletal muscle)
vWeight loss due to catabolism of fat and protein (unless balanced by food intake)
vIn children small doses produce a positive nitrogen balance since T4 stimulates growth. not much nitrogen is excreted
vT4 is required for hepatic conversion of carotene to vitamin A in the liver → carotenemia
vLack of T4 → myxedema (puffiness of the skin due to lack of degradation of proteins, polysaccharides and hyaluronic acid)
vincreased erythropoiesis (due to increased demand for O2 because of increased tissue building effect of thyroid hormones )
Effects on the Cardiovascular system
Rise in body temperature activates heat dissipation mechanisms:
- Cutaneous vasodilation → Decreased resistance to peripheral blood flow (RAAS gets activated ) → Increase of renal Na+ and H2O reabsorption to expand blood volume
vasodilation occurs more in extremities
- Increase of cardiac output by T3/T4 and catecholamines shorten circulation time of blood by increasing pulse pressure and cardiac rate
- increased blood volume-> increased work of the heart-> increased blood pressure
T3/T4 increase strong and active myosin that using more ATP; reduce expression of myosin filaments that are weaker and have lower ATPase activity
Net result: Increased heart rate and force of contraction
Mechanism of action on the heart
- Triggered by T3 (from circulation since myocytes lack the deiodinase to form T3 from T4)
- Genes turned on: α-myosin heavy chain (high ATPase activity), sarcoplasmic reticulum Ca2+ ATPase, β- adrenergic receptors, G-proteins, Na+-K+ ATPase, some K + channels.(help in increased forcefull contractions )
- Genes inhibited: β-myosin heavy chain (low ATPase activity-> lower contraction stress ), two types of adenyl cyclase, T3 nuclear receptor, Na+-Ca2+ exchanger
Synergism with catecholamines
- Catecholamines from adrenal medulla have similar effects as T4/T3 but of shorter duration
- > Increase in the metabolic rate, stimulation of the nervous system, cardiovascular effects
T3/T4 positively modulate catecholamine effects
- Blocking β-adrenergic receptors reduces action of T3/T4
Beta blockers and thyroid storms
Thryoid storms: sudden increased T3/T4 release
- Thyroid hormone toxicity induced by infection, trauma, drugs etc. Molecular mechanism unclear but results in high temp. up to 106 F, heart rate 200 bpm etc.
- May be lethal if not treated immediately
Effects of thyroid hormones on the nervous system
neurones don’t convert T4 to T3 themselves but have astrocytes to do it
Astrocytes convert T4 to T3, which is then transported to neurones vua MCT8 or MCT10
Results in Increased responsiveness to catecholamines
What is the impact of Lack of T3/T4 during development
Effects of TH on Skeletal Muscle
- Hyperthyroidism: Muscle weakness due to increased protein catabolism.
- Hypothyroid: Muscle weakness (as no impact on ATP production, oxidative phosphorylation), cramps, stiffness.
- In both cases relationship between myopathy and thyroxin levels unclear.
Effects of TH on carbohydrate metabolism
Thyroid hormones increase absorption of carbohydrate from the gastrointestinal tract
effects of TH on cholesterol metabolism
– Decrease of cholesterol levels independent of calorigenic action
– Due to the increase of LDL receptors in the liver (→ hepatic clearance of cholesterol)
Effects Of The Thyroid Hormones On The Reproductive System
- Required for normal follicular development and ovulation in the female
- Required for the normal maintenance of pregnancyl as TH are required for CL maintenance
- Required for normal spermatogenesis in the male
Effects Of The Thyroid Hormones In Growth and Tissue Development
- Increase growth and maturation of bone
- Increase growth and maturation of epidermis, hair follicles and nails
- Increase rate and force of skeletal muscle contraction
- Inhibits synthesis and increases degradation of mucopolysaccharides in subcutaneous tissue
__ may have myxodema
hypothyroidism may have myxodema (puffiness associated with mucopolysaccharides accumulation under skin)
What is hypothyrodism usually treated with?
Levothyroxine (synthetic T4) due to longer half life
Symtomps and signs of hyporthyrodism
Symptoms – fatigability, coldness, weight loss, constipation, low voice
Signs – Cool skin, dry skin, swelling of face/hands/legs, slow reflexes, myxedema
Infants and children – Retardation, short stature, swelling of face/hands, possible deafness
Types of hypothyrodism
- Primary – Thyroid gland failure (most common cause)
- Secondary – Pituitary failure (TSH deficiency)
- Tertiary – Hypothalamic failure (TRH deficiency)
- Peripheral resistance to action of thyroid hormone
WHat is the level of iodine deficiency that would lead to goiter? WHat are the possble causes?
How does goiter progress?
- Iodine deficiency at <50 μg/day (can also be caused by perchlorates and other treatments
- Elevated TSH (decreased negative feedback) results eventually in enlargement of the thyroid.
Iodine deficiency and goiter
Iodine deficiency during pregnancy results in neurological damage (cretinism: intellectual impairment, deafness, paralysis).
T3 and T4 are one of the earliest hormones to be synthesized by the fetus
Large doses of iodine and goiter
Large doses of iodine may inhibit synthesis and excretion of thyroid hormones
Is iodine deficiency still a problem?
Why?
Iodine deficiency is still a huge problem world-wide
- Thyroid hormones are essential for growth and neural development
- Hypothyroid children → Slowed bone growth. Delay of epiphysial closure
- In hypothyroid children GH secretion is depressed
- T3/T4 potentiate the effect of GH on tissues ->inhibition of growth
- if occurs in newborn infants more severe effects including mental retardation, stunted growth, delayed puberty
What is myxedema?
Advanced hypothyrodism
Hypothyrodism and elderly
- T4 levels gradually decrease by as much as 50 % in elderly
- They may gradually develop hypothyroidism (“thyropause”)
- become more susceptible to winter
Untreated hypothyroidism during the winter :
- progressive weakness,
- hypoventilation,
- hypoglycemia,
- Hypothermia,
- progressing to coma and death
Hashimoto’s Disease- causes
- Autoimmune disease
- Major cause of hypothyroid disorders in areas of iodine sufficiency
- Goiter in younger patients
- No goiter in older patients
- Autoimmune response is against TPO and/or Tg
Hashimoto’s lab values
High TSH, Low T4, Anti-TPO Ab, Anti-TG Ab
Hashimoto’s treatment
Treat with Levothyroxine (T4)
results in less T3 and T4 production
Grave’s disease
What is it?
Symptoms?
Ethiology
graves disease is a common cause of hyperthyroidism which causes enlargement of thyroid
Symptoms – Palpitations, nervousness, fatigue, diarrhea, sweating, heat intolerance i.e. accelerated metabolism, bulging eyes
Signs – Thyroid enlargement (?), tremor
extracellular domain can be released into the circulation
auto-immunity can be developed
leads to AB binding to TSH receptor which can result in signalling. These AB act as fi there’s a lot of TSH
This leads to increased activity of thyroid gland, increased growth, high levels of T3 and T4
What is the most common cause of hyperthyrodism?
Grave’s disease
What is Grave’s a result of?
Result of immune system producing anti-TSH receptor antibodies
- Binding of Ab to receptor induces signal transduction of TSH pathway resulting in T4/T3 production without TSH
- T4 suppresses TSH release from pituitary (i.e. negative feedback)
