Thyroid Flashcards
what are the three types of hormones
Peptide
steroid
amine
what type of hormone is thyroid hormone
Amine as it is made from tryosine
- has this is common with other steroid hormones such as dopamine
what is thyroid hormone originally made from
Tryosine
how does T3 and T4 form
- Tryosine has an iodine put on it and this produces monoidotryosine
- another iodine is stuck on it and you produce di-iodotryosine
- another iodine is stuck on and you produce liothyronine (T3)
- another iodine is stuck on and you produce levothyroxine (T4)
which is produced is larger amounts T3. or T4
T4
What was the first organism to trap iodine
seaweed
what form is iodine stored in
oxidised iodine - this is lipophilic so you can store it in the thyroid gland
- therefore the thyroid gland has to have some kind of oxidation properly
what does the thyroid gland do to iodine when it enters
- it attaches iodine to thyroglobulin(a protein) which can then be used in transport
what does the thyroid hormone do to metabolism
thyroid hormone stimulates metabolism
How much does the thyroid gland weigh
15-20g
How large are the lobes in the thyroid gland
The lobes are about 2cm thick and 4cm long
Describe the structure of the thyroid
Divided into two lobes – sometimes the right lobe is larger than the left lob
Isthmus in the middle
what part is going to be papable if the thyroid gland enlarges first and why
The right lobe is normally larger, so when the whole gland enlarges the right is usually the first one to become palpable.
describe the blood flow for the thyroid gland and what is its clinical relevance
- receives more blood flow per unit volume of any of the organs in the body
- can hear a bruit in graves disease
all iodine is ..
trapped in the thyroid gland in a short period
describe the embryo development of the thyroid
- develops over 24 days
- made from 2 pharyngeal pouches and 1 groove, more over following days
- then we develop additional grooves and pouches over the following days.
- Pouch 3 - inferior parathyroid and thymus
- Pouch 4 - superior parathyroid and ultimobranchial body
Ultimobranchial body - C-cells - Thyroid diverticulum starts at foramen cecum and descends Non duct closure - thyroglossal cyst
What is a pharyngeal pouch
endodermal outpouching of pharynx
how do follicular cells vary
- they vary in height and activity, as they become more active they are converted from cuboidal to columnar
how many follicles are there per lobule in the thyroid
20-40 follicles per lobule - single artery
what fluid is present in the thyroid follicle
colloid
what happens in destructive thyroditisi
- follicular cells are damaged
- this leads to all the thyroid hormones being released so the levels initially rise and then they fall down and go to nothing
Describe the structure of a thyroid follicular cell
- The apex has numerous microvilli extending into the colloid
- The cytoplasm has extensive ER and microsomes
- Thyroglobulin has a carbohydrate portion so there is predominant Golgi apparatus
- Has to break down Tg so numerous lysosomes
Describe how the thyroid follicular cell works
So there is a TSH receptor – this is a sodium iodine symporter because if you are bringin in iodine you need to bring in sodium to maintina electroneutraliing
- 2 sodiums and an iodine
- Iodine this goes into the colloid via PDS (pendrin)
- TPO – thyroid peroxidase
- ER – produce thyroglobulin
- Thyroglobulin transported into the colloid where it become iodinate this will then be digested inside the thyroid follicular cell to release MIT AND DIT and also T3 and T4
- D1 convers T4 to T3
What does mutations in pendrin(PDS) lead to
mutations in PDS lead to hypothyroidism and deafness as it is also expressed in the semi circular canals
How does the thyroid cell take up iodine and transport it into the colloid
A means of iodide uptake from the circulation – a thyroidal sodium iodine symporter NIS – and of transporting it to the colloid – pendrin PDS
What does the TSH receptor on the thyroid follicular cell do
A TSH receptor to receive signals from the pituitary gland - TSHR
What oxidised iodide
thyroid peroxidase TPO
what recycles iodide
– iodotyrosine dehalogenase 1 (IYD)
what converts T4 to T3
– thyroidal type 1 and type 2 deiodinases.
what provides energy for the thyroid follicular cell to work
Nak ATPase
describe how T3 and T4 are formed in the thyroid follicular cell
- TSH binds to the TSH receptor
- 2 sodium and an iodide go in
- Iodide then goes into the colloid out of the thyroid follicular cell via pendrin (PDS)
- DUOX2 provides hydrogen peroxide that. is needed to activate TPO
- TPO is thyroid peroxides
- ER and golgi produce thyroglobulin
- thyroglobulin is then transported into the colloid out of the thyroid follicular cell where it combines with the iodide ions
- this moves back into he thyroid follicular cell and is then digested inside the cell to release MIT and DIT as well as T3 and T4
- D1 – deodinese enzyme that converts T4 to T3
- MIT and DIT have there iodine recycled
what do mutations in the PDS (pendrin) lead to
Mutations in PDS lead to hypothyroidism and also sensory neural deafness as it is expressed in the semi circular cannals
what do autoantibodies against TPO mean
autoantibodies against TPO are in autoimmune thyroid diseases
what is T4 release inhibited by
T4 release from thyroid cells is inhibited by iodide
- This action is probably mediated by iodide inhibiting adenylyl cyclase activity
the more iodine on a Tg molecule..
the more iodine on a Tg molecule, the more resistant it becomes to hydrolysis and release of T3/T4
what causes hyperplasia of the Thyroid
TSH
describe the control of thyroid hormone release
- works via a negative feedback loop
- TRH from the hypothalamus stimulates TSH in the pituitary
- TSH goes to the thyroid and stimulates the production of T4 and T3
what does TRH stand for
thyrotropin releasing hormone
what does TSH stand for
thyrotropin stimulating hormone
- produced in the thyrotroph cells in the pituitary gland
what happens to T4 in the gut
In the gut T4 gets glycolated and this enables it to be excreted into the gut
what converts T4 to T3
deiodinease enzymes
what is the difference between D1 and D2
D1 upregulated by high TH
D2 downregulated by high TH
D1 has a higher Km than D2 this means that D1 is less deficiency than D2 in converting T4 to T3
D1 in plasma membrane
D2 in the ER
why is D2 unregulated in a fall in T4 and down regulated in high T4
Fall in T4 ——> D2 upregulated to convert more T4 to T3; buffers changes in T4 before leading to increased TRH and TSH
High T4 ———> D2 down regulated to protect brain tissue from excess TH
what up regulates D3
Ischaemia and hypoxia upregulate D3 in myocardium and brain so metabolism slows down.
why are steroids useful in thyrotoxicosis
High dose steroids inhibit both D1 and D2, and activate D3
D1
- substrate
- distribution
- intracellular location
- function
- hypothyroidism
- hyperthyroidism
substrate - T3>T4>T3
Distribution - liver, kidney, muscle and thyroid
intracellular location - plasma membrane
function: plasma T3 production
hypothyroidism - down-regulated
hyperthyroidism - unregulated
D2
- substrate
- distribution
- intracellular location
- function
- hypothyroidism
- hyperthyroidism
- substrate - T4>T3
- distribution - brain and pituitary, brown fat, skeletal muscle
- intracellular location - ER
- function - local T3 production
- hypothyroidism - unregulated
- hyperthyroidism - downreugulated
D3
- substrate
- distribution
- intracellular location
- function
- hypothyroidism
- hyperthyroidism
- substrate - T3>T4
- distribution - brain, placenta, foetus
- intracellular location - ER
- function - T3 degradation
- hypothyroidism - dowregulated
- hyperthyroidism - unregulated
what is the main portion that thyroid binds to in the blood
thyroid binding globulin
- some bids to albumin but not as strongly - but therefore albumin levels changing can have an effect on thyroid function
- some binds to transthyretin
what does TBG have a higher affinity for
TBG affinity highest for T4 (20x T3 affinity)
what inhibits TBG binding
Binding inhibited by phenytoin, salicylate, furosemide
what effects the level of free T4 and T3
TBG
describe an example of how changing TBG effect free thyroid levels
example of this is in pregnancy, in pregnancy oestrogen levels is higher, oestrogen attaches little side chains to TBG and increases the half life of TBG so it binds more of the thyroid hormone so it reduces the amount of free thyroid hormone so hypothyroidism in pregnancy can happen as T4 levels go down and causes negative feedback –therefore some people take thyroxine when you pregnant by 25% increase
name the three types of hormones
steroid
peptides
amines
name the three types of hormone receptors
nucleus
cytoplasm
cell surface
describe in terms of genetic elements what happens when the thyroid binds to the thyroid hormone receptor
- Thyroid hormone enters the cell and there is some transporters allowed to enter the cell
- Binds to the thyroid hormone receptor and causes the complex to fall apart
- Converts a retonic acid receptor and a coactivator protein and this can cause transcription to be activated
what type of receptor is the thyroid hormone receptor
it is a homodimer
what are the transports that regulate thyroid hormone uptake
MCT8
MCT10
OATP1C1
name the effects of the thyroid hormone
Increase BMR
Increased o2 consumption
Increased rates ATP hydrolysis
“blowing on a smouldering fire”
Increased fat mobilisiation
Enhanced fat oxidation
Cholesterol high in hypothyroidism
Carbohydrate metabolism:
Increased glucose entry into cells
Increased gluconeogenesis
Increased glycogenolysis
Growth retardation in thyroid deficiency
Fetal brain development - iodine supplementation for women seeking fertility
Heart rate, contractility, cardiac output
Vasodilation - enhanced blood flow to organs (including thyroid itself)
Neurologically slow or jittery
Mostly metabolic effects – easier to think amount what the thyroid hromoen effects are - by presentation of patients that have underactive thyroid and overactive thyroid
what is the difference between hyperthyroidism and thyroxicosis
hyperthyroidism – means thyroid gland producing to much thyroid hormone
Thyrotoxicosis – state of too much thyroid hormone – can be due to hyperthyroidism or damage to the thyroid gland or from someone who is taking too much thyroid hormone themselves
name the effects of hyperthryodism
- cardiovascular system
- metabolism
- nervous system
- eyes
- skin
- GI tract
- bone
- haematological
- reproduction
cardiovascular
- 20% toxic patients have AF - increases basal metabolic rate
- thyroid hormone increases alpha to beta myosin ratio so has a positive inotropic effect
- increases NO - decreases peripheral resistance
metbaolism
- Increased BMR
- Increased Appetite
- Heat intolerance
- Protein and lipid degradation - increase the basal metabolic rate so need to supply fuel
- Weight loss and myopathy - protein loss due to supplying fuel
- Increased insulin turnover
- Increased gluconeogenesis
- Reduced insulin secretion
nerouvs systemic m
- seizures
- hyperphagia - increase basal metabolic rate - increase in the expression of D2 in the hypothalamus, so there is a local increase in TH. This activates AgRP neurons and inhibits POMC neurons leading to an increase in appetite.
eyes
- autoimmune tissue effects - in graves leads the eyes to pop out
skin
- plummers nails
- pretibial myxoedema (rash you get in graves)
GI tract
- increase in appetite
- weight loss
- increase in motility
- transaminitus
bones
- accelerated osteoclast activity
- hyperclaemia
- osteoporosis - increase osteoclast activity this can therefore lead to hyperclaemia and osteoporosis
haemotalogical
- pernicious anaemia - more to do with autoimmune part
- B12 deficiency
reproduciotn
- Oligomenorrhoea
- Gynecomastia
- Erectile dysfunction - androgens are converted to oesteotrogne
why do patients with hyperthrydosim fill hot
- increase in basal metabolic rate produces an increase in heat
- need to get rid of heat therefore the body sends more blood to the skin - increase in CO increases blood to the skin
what is graves disease
- autoimmune condition against the thyroid resulting in hyperthrydoism
how does graves disease cause hyperthryodism
Graves is characterised by the production of the antibody against the TSH receptor and it activates the TSH receptor and does all of the things the thyroid does – most of the lymphocytes in a pathological specimen of a graves disease are T cells
- antibodies are from thyroid B cells
describe the autoantibodies that can develop against the thyroid
- against TSHR - leading to graves disease
- Against TPO - leading to hasmitos thyroiditis
- against thryoglobumin
why does graves eye disease develop
- the TSH receptor is expressed on retroorbital fibrocytes, therefore the fibrocytes secrete GAGs and become fibrotic
- this causes the growth of cells behind the eye and leads to proturisis of the eye
what are the risk factors of Graves disease
- HLA Status
- Infection – can be a trigger
- Stress – in graves disease stress is a trigger
- Female sex – more common – may be due to genes expressed on the X chromosome when men do get it it tend to be more sever and diffiuclt ot treat
name some other causes of thyrotoxicosis
- toxic multi nodular goatees
- toxic andeoma
- excess iodine - most common
- Amiodarone – anti arrhtymic – contains iodine
- HCG – this is a hormone that we measure when we are doing a pregnancy test – looks like TSH structurally
- Thyroiditis
- Struma ovarii– teratoma – becomes highly differetoated into thyroid tissue
- TSHoma
- Hamburger thyrotoxicosis – a lot of thyroid gland ended up in hamburgers in the early 1980s
what causes a toxic multinodulaur goitre
this happens when the TSH receptor in one cell mutates and becomes active - this can cause hyperplasia and causes the cells to divide therefore you have two cels with the mutated receptor and then they divide and so on
how can a toxic adnoma be seen
- thyroid gland traps iodine therefore give the contract I-123 or technetium and the adenoma thyroid gland will take up and stored th iodine
how do you treat a toxic adenoma
- radioactive iodine
- this radioactive iodine can also be used in treating graves disease but this can destroy the thyroid gland
How do you diagnose hyperthyroidism
Blood test
Elevated T4 and T3
Suppressed TSH
how do you treat hyperthyroidism
Thionamide drugs
- Propylthiouracil
- Carbimazole
Radioactive Iodine I-131
Thyroidectomy
describe the symptoms in hypothyroidism
- skin
- cardiovascular
- GI tract
- nerves, msucles, bone
- renal
- haematological
- metabolism and endocrine
Skin
- the skin and hair becomes dry
- outer 1/3 of the eyebrow is lost
- reduced sweat and sebum
- wounds heal slowly
cardiovascular
- reduced cutaneous circulation so you have increase sensitivity to cold
- sinus bradycardia
- LDL cholesterol increases
- J waves of hypothermia
GI
- reduced appetite
- constipation
- weight gain due to fluid retention by hydrophilic glycoproteins in the tissue
nerves, muscle, bones
- impaired fatal brain development
- dementia
- slow relaxing reflexes
- growth retardation - result in dwarfism, leads to epiphyseal dysgensis
renal
- reduced GFR
- mild hyponatremia - retention of water by hydrophilic deposits in the tissue
haemotological
- normochornic and mormocytic anaemia
- decreased red cell mass and less EPO
- B12 deficiency?
metabolism and endocrine
- delayed puberty
- reduced libido
- erectile dysfunction
- reduced Basal metabolic rate
- decreased GLUT4 sitmualtion
what are the causes of hypothyroidism
Hashimoto’s disease – TSH goes up and T4 goes down
Endemic goitre
Lithium - this inhibits TH release
Cabbage
Infiltrative diseases – such as amyloid
Pendred’s syndrome
Hypopituitarism – TSH goes down and T4 goes down
what is the recommended iodine intake for pregnant and lactating women
Pregnant and lactating women: 250μg per day
200ml cows milk: 80μg
200ml almond milk: ZERO
how much does pregnacare conception tablet and prenacare regular tablet contain of iodine
Pregnacare conception: 200μg per tablet
Pregnacare regular: 140μg per tablet
what is creatinism
- lived where there is low levels of iodine in the soil therefore they developed hypothyroidism,
- have large goitres
- mothers had hypothyroidism therefore the babies brain was impaired
what does hypothyroidism look like in a blood test
Hight TSH
- Low T4
what is a treatment of hypothrydoidsm
levothyroxine - covered to T4 when entering the body
can have
- liothyronine - T3 tablets but not in the UK
- armour thyroid - not in the UK
