L3 - Thyroid Hormone Physiology Flashcards
THYROID GLAND BLOOD SUPPLY
i) which two arteries supply the thyroid? what main arteries are they a branch of?
ii) what other artery may also supply the thyroid? which main vessel is this a branch of?
iii) what are the three main veins that drain the thyroid gland? which vein does each drain into?
iv) which two lymph nodes does the thyroid initially drain to? which three LNs does it then consequently drain to?
i) superior thyroid artery towards back (branch of the ext carotid)
inferior thyroid artery towards front (branch of the thyrocervical trunk/subclavian)
ii) thyroidea ima artery may also supply - branch of the aortic arch or bc trunk
iii) veins 1) superior thyroid vein - drains to IJV
2) middle thyroid vein - drains to IJV
3) inferior thyroid vein - drains to innominate veins
iv) initial drainage to pretracheal and prelaryngeal nodes
- then to deep cervical, supraclavicular and mediastinal LNs
HISTOLOGY OF THE THYROID GLAND
i) what type of cells form a monolayer around a follicle?
ii) what is found in the centre of the follicle? what is the function of this?
iii) which cells produce thyroid hormones?
i) epithelial cells
ii) colloid is found at the centre of follicles and these act as a reservoir for thyroid hormone
iii) follicular/epithelial cells produce thyroid hormone
THYROID HORMONE SYNTHESIS
i) what are the three primary hormones secreted by the TG?
ii) what amino acid is the basis for thyroid hormones? what is added to it to make MIT and DIT?
iii) which thyroid hormone is composed of
a) MIT + DIT
b) DIT + DIT
iv) what are the two isomers of T3? which one is the active version?
i) TG secretes T3, T4 and calcitonin
ii) tyrosine is the amino acid base and iodine is added to make MIT and DIT
iii) MIT + DIT = T3
DIT + DIT = T4
iv) T3 = T3 and reverse T3
- reverse T3 is biologically inactive
THYROID HORMONE PHYSIOL
i) what degrades MIT and DIT and what happens to the degraded components?
ii) where are T3 and T4 made?
iii) what form is 95% of the thyroid hormone leaving the thyroid gland in?
i) halogenases degrade MIT and DIT
- this frees the iodide and it can be re-utilised by combining it with thyroglobulin (to re make T3/T4)
ii) T3 and T4 are made in the follicular cells
iii) 95% of the hormone made by the TG is in the form of T4
THYROID HORMONE ACTION
i) where are thyroid hormone receptors found?
ii) what is the effect of thyroid hormones when they interact with their receptors?
iii) what do thyroid hormones predominantly control?
iv) name three scenarios where thyroid hormone will be increased
v) what part of developement are thyroid hormones essential for?
i) intracellularly
ii) cause gene transcription and protein synthesis
iii) thyroid hormones control basal metabolic rate
iv) thyroid hormone will be increased in carb metabolism, synth/mobilisation/degrad of lipids and in protein synthesis
v) thyroid hormones are important for development for the CNS - especially myelination of nerve fibres
HORMONE SYNTH/PHYSIOL
i) label A, B and C on the diagram
ii) what happens to T4 in the target tissues? what enzymes allow this?
iii) how many x more biologically active is T3 than T4?
iv) what % of the biologically active thyroid hormone in the cell is T3?
v) what are the plasma half lives for T3 and T4?
i) A = calcitonin
B = T4
C = T3
ii) T4 gets converted to T3 (80%) or reverse T3 (20%)
- conversion by deiodinase enzymes
iii) T3 is 40 times more biologically active than T4
iv) 90% of biol active thyroid hormone in a cell is T3
v) half life T3 = one day
T4 = 6-8 days
CIRCULATING THYROID HORMONES
i) is there more bound or free T3/T4 circulating in the blood?
ii) name three proteins that thyroid hormones bind to
iii) in what scenario does the amount of binding proteins increase?
iv) what % of thyroid hormones are free and biologically active?
i) most is bound to proteins
ii) thyroxine binding globulin, thyroxine binding albumin, thyroxine binding prealbumin
iii) increase in binding proteins in pregnancy
iv) 0.04% of free T4 and 0.4% of free T3
CONTROL OF THYROID HORMONE SECRETION
i) what hormone is released by the hypothalamus? what doe this cause the pituitary gland to release?
ii) which two hormones do T3 and T4 negatively feed back to?
iii) name one place where T4 is converted to T3 and reverse T3?
iv) how are thyroid hormones they excreted?
v) where are small peptides and dopamine secreted from? what do they control secretion of?
i) HT releases TRH which causes PG to release TSH
ii) T3 and T4 neg feedback to TSH and TRH
iii) T4 is converted to T3 in the liver
iv) they are conjugated and excreted in bile
v) small peptides and DA are secreted from the median eminence (of HT) and control secretion of gonadotropes, lactotropes etc etc in the pituitary gland
CLINICAL SYNDROMES - HYPERTHYROIDISM
i) what is the name of this condition
ii) name three ways in which it can be treated
iii) which two drugs may be used to treat it?
iv) what feature may be prominent in these patients?
i) Graves disease
ii) treat with drugs, surgical removal of the thyroid or radioactive iodine
iii) carbimazole or propylthiouracil
iv) prominent thyroid gland
CORE DRUG - LEVOTHYROXINE
i) what is this principally used to treat?
ii) what other condition may it be useful in?
iii) what is its oral bioavail?
iv) how is it metabolised and how is it excreted?
v) what is its approx half life?
vi) name four adverse effects at excessive doses
i) hypothyroidism
ii) can also be used to supress TSH secretion in the treatment of some thyroid tumours
iii) 100%
iv) metabolised in the liver (glucoronidation) and excreted in the urine
v) 7 day half life
vi) adverse effects - palpitations, arrhythmias, diarrhoea, tremor, insomnia
CORE DRUG - CARBIMAZOLE
i) what is it principally used for?
ii) what type of drug is it?
iii) what does the active form of the drug do?
iv) what is its oral bioavail and how quickly is it metabolised?
v) what is its approx half life and how is it excreted?
vi) which two adverse effects are common? what can these be treated with?
vii) what are two rare side effects?
i) used to decrease thyroid hormone levels
ii) a pro drug
iii) converted to methimazole which prevents peroxidases iodinating the tyrosine residudes on thyroglobulin therefore reducing thyroid hormone production
iv) 90% bioavail and rapidly metab to methimazole
v) half life 6 hrs and excreted in urine
vi) common adverse effects are rashes and pruritis (tx w antihistamines)
vii) rare side effects are neutropenia and agranulocytosis (low WBC causing neutropenia)
CORE DRUG - PROPYLTHIOURACIL
i) what is it principally used to treat? how does it do this?
ii) at what point of life is it the drug of choice?
iii) what is its oral bioavail and how is it metabolised?
iv) what is its approx half life and how is it excreted?
v) name two common adverse effects and how these can be treated
vi) name two more serious side effects
i) used to treat hyperthyroidism by inhibiting thyroperoxidase (aids TH synthesis)
- inhibiting deiodinases that convert T4 to T4
ii) drug of choice for hyperthyroidism in the first trimester of pregnancy (as carbimazole is teratogenic)
iii) 80-95% oral bioavail and metabolised in the liver (hepatic glucuronidation)
iv) half life two hours and has renal secretion
v) common SEs = rashes and pruritis tx with antihistamines
vi) serious SEs = agranulocytosis and liver injury (can be fatal)
DRUG TREATMENT OVERVIEW
i) which drug is used to treat hypothyroidism
ii) which drug used to treat hyperthyroidism is a pro drug? what is the name of the active form?
iii) which drug is the drug of choice for hyperthyroidsm in the first trimester of pregnancy? why?
iv) which enzyme do drugs for hyperthyroidism target? what effect does this ultimately have?
i) thyroxine
ii) carbimazole is a pro drug and its converted to methimazole
iii) propylthiouracil is used in 1st trimester pregnancy as carbimazole is teratogenic
iv) hyperthyroidism drugs eg carbim and propylthio target peroxidases and prevent them iodinating tyrosine residues on thryoglobulin which causes a reduction in thyroid hormones made
