Thyroid Hormone Physiology Flashcards
In a series of lectures in 1905 to the Royal College of Physicians in London, Starling first used the term ‘hormone’ - what did this describe?
‘Hormone’ described those chemical messengers which ‘have to be carried from the organ where they are produced to the organ which they affect by means of the blood stream’
The thyroid gland plays a pivotal role in what?
human and animal physiology
The thyroid gland hormones determine what?
the rate at which chemical reactions take place in cells
What is this image showing?
The anterior and posterior parts of the thryoid gland
What does the thyroid gland look like?
The thyroid is a butterfly-shaped gland that sits low on the front of the neck.
It is also lumpy / has nodules
How many lobes in the thyroid gland?
What joins them?
Two - left and right lobe
Two lobes are joined by a small bridge called the isthmus
Posterior view of thyroid gland - it wraps around the …
trachea - not the whole way round
Blood supply to the thyroid:
What Arteries? branches of what?
sometimes the … … artery is present which is a branch from the arch of … or brachiocephalic trunk can be found
superior thyroid artery - branch of external carotid artery
inferior thyroid artery - from thyrocervical trunk branch of the first part of subclavian artery
thyroidea ima artery
Blood supply to the thyroid: Veins
3 major veins drain the thyroid gland. These are…
they drain to what?
Superior thyroid vein drains to the internal jugular vein
middle thyroid vein drains to the internal jugular vein
inferior thyroid vein drains to innominate veins
Lymphatic drainage of the thyroid gland:
The drainage is to …
pretracheal and prelaryngeal then to deep cervical, supraclavicular and mediastinal lymph nodes
Nerve supply of thyroid - isnt innervated but is the risk during a thyroidectomy? also want to avoid removing what?
good surgeon figure will be near to
surgeon who doesnt know what they are doing - can damage the recurrent laryngeal nerves when they do thyroidectomy
avoid removing parathyroid
zero
Microscopic structure of the thyroid
The thyroid gland is composed of … each consisting of a … of epithelial cells enclosing a large core of viscous homogenous …
this acts as a reservoir of … …
follicles - each consisting of a monolayer of epithelial cells enclosing a large core of viscous, homogenous colloid
thyroid hormone reservoir
The primary hormones secreted by the thyroid gland are …, … and …
tri-iodothyronine (T3), tetraiodothyronine (T4) and calcitonin
Calcitonin is concerned with … homeostasis, is secreted independently of the other thyroid hormones
calcium homeostasis
What is this diagram showing?
thyroid hormone physiology
Chemical structures of thyroid hormones
MIT and DIT are rapidly degraded by … to free the …, which is then re-utilised by combination with …
The T3 and T4 leave the … cells and enter the blood stream for distribution to the …
approximately … % of the thyroid hormone leaving the thyroid gland is in the form of …
halogenases to free iodide which is then re-utilised by combination with thyroglobulin
The T3 and T4 leave the follicular cells and enter the blood stream for distribution to the target tissues
Approximately 95% of the thyroid hormone leaving the thyroid gland is in the form of T4 (thyroxine)
What structures are shown? left to right
tyrosine, thyroxine (T4), Triiodothyronine (T3), Reverse T3 (inactive)
2 biological active thyroid hormone (… and …), reverse … is inactive
T4 product of what?
… largely produced in other tissues
… gland stores large quantities of thyroid hormones
T3 & T4, reverse T3 is inactive
T4 product of thyroid gland
T3 largely produced in other tissues
Thyroid gland stores large quantities of thyroid hormones
Mechanism of thyroid hormone action
The receptors for the thyroid hormones are …, specifically …
The effect of the interaction of the thyroid hormones with their receptors is to influence … … and thus protein …;
intracellular, specifically nuclear
influence gene transcription, thus protein synthesis
Thyroid hormones control rate at which what reactions take place?
chemical reactions take place in every cell in the body
The main effect of the thyroid hormones is to increase basal metabolic rate:
increased in … metabolism
increased in the synthesis, mobilisation and degradation of …
increased protein …
carbohydrate
lipids
protein synthesis
Thyroid hormones are essential for the normal development of the …, especially … of … fibres
CNS, especially myelination of nerve fibres
Overview of thyroid hormone biosynthesis:
Thyroid follicles - each composed of a single layer of epithelial cells which surrounds a fluid substance called …
the follicle cells produce a glycoprotein called … - secreted into lumen
these molecules contain the amino acid … residues and generate the thyroid …
In between thyroid follicles in the connective tissue there are scattered … “…” cells
Which form is more active?
These produce the hormone called … - not a thyroid hormone - involved in … and … regulation
thyroid has a rich … supply - multiple blood vessels in between the thyroid follicles - two types of hormones?
The The thyroid gland secretes …% T4 and …% T3
thyroid follicles - each composed of a single layer of epithelial cells which surrounds a fluid substance called colloid
the follicle cells produce a glycoprotein called thyroglobulin - secreted into lumen
these molecules contain the amino acid tyrosine residues and generate the thyroid hormones
In between thyroid follicles in the connective tissue there are scattered parafollicular “C” cells
C cells produce the hormone called calcitonin - not a thyroid hormone - involved in calcium and phosphate regulation
thyroid has a rich vascular supply - multiple blood vessels in between the thyroid follicles - two types of hormones
thyroxine (T4) or triiodothyronine (T3)
The thyroid gland secretes 90% T4 and 10% T3
T3 is more active
Regulation of thyroid hormone synthesis:
Production of thyroid hormones T3 and T4 are stimulated by a hormone called
TSH (thyroid stimulating hormone)
TRH stands for what?
where is it released from?
Thyrotropin releasing hormone
hypothalamus
TSH stands for what?
where is it released from?
Thyroid stimulating hormone / thyrotropin
Anterior pituitary
Within the target tissues, … enzymes convert the T4 to either … (80%) or … (20%)
Deiodinase enzymes convert T4 to either T3 (80%) or reverse-T3 (20%)
T3 has a biological … approximately 40 times greater than that of T4, whilst reverse-T3 is biologically …
activity
reverse-T3 inactive
Up to 90% of the biologically active thyroid hormone within the cell is in the form of what?
T3
The plasma half-life of T4 is …-… days whilst that of T3 is … day
T4 - 6-8 days
T3 - one day
The thyroid hormones in the blood are bound to …
They bind to Thyroxine binding …, thyroxine binding … and thyroxine binding …
a very small amount is unbound
this is called … and biologically …
… T4 = what %?
… T3 = what %?
proteins
Thyroxine binding globulin, thyroxine binding albumin, thyroxine binding prealbumin
very small amount unbound - free and biologically active
Free T4 - 0.04% , Free T3 -0.4%
Control of thyroid hormone secretion
… increases secretion of …
… stimulates secretion of T3 and T4
T3 and T4 inhibit … direactly and indirectly by suppressing release of …
T4 converted to … in liver and other tissues
TRH increases secretion of TSH
TSH stimulates secretion of T3 and T4
T3 and T4 inhibit TSH directly and indirectly by suppressing release of TRH
T4 converted to T3 in liver and other tissues
Hypothalamic releasing hormones
The median … secretes small peptides and …
These hormones control the secretion of …, …, …, …, and … (all end in tropes)
Discovery of these hormones and the blood supply connecting the hypothalamus and pituitary led to the Nobel Prize physiology/medicine in … for Andrew Schally and Roger Guillemin
The median eminence secretes small peptides and dopamine
These hormones control the secretion of gonadotropes, somatotropes, lactotropes, corticotropes, and thyrotropes
Discovery of these hormones and the blood supply connecting the hypothalamus and pituitary led to the Nobel Prize physiology/medicine in 1977 for Andrew Schally and Roger Guillemin
TRH increase secretion of …
… stimulates secretion of both … and …
These inhibit … directly and indirectly by suppressing release of TRH
… converted to T3 in … and other tissues
Both … and … conjugated and excreted in …
TRH increase secretion of TSH
TSH stimulates secretion of both T3 and T4
These inhibit TSH directly and indirectly by suppressing release of TRH
T4 converted to T3 in liver and other tissues
Both T4 and T3 conjugated and excreted in bile
What is shown in this image? (thyroid hormone physiology)
10 yo with severe hypothyroidism due to primary myxedema before and after treatment
What is shown in this image?
prominent thyroid gland - goitre - was known as derbyshire neck in the past
Hyperthyroidism
treated by … thyroid hormones with drugs or … out the thyroid or radioactive iodine
reducing
or removing thyroid (surgery)
Hypothyroidism
treated with … therapy
what is used?
replacement therapy
T4 (thyroxine)
… is used to treat thyroid deficiency
It can be used to suppress … secretion in the treatment of some thyroid …
it can be given by … or injection
levothyroxine
used to suppress TSH secretion in the treatment of some thyroid tumours
it can be given by mouth or by injection
Levothyroxine
oral bioavailability - ?
protein binding - ?
metabolism ?
half-life ?
excretion ?
standard maintenance dose?
100%
> 99%
metabolised in liver by glucoronidation
half-life - approx 7 days
20-40% excreted in urine
maintenance dose - 50-100 micrograms daily
Levothyroxine - adverse effects
at excessive doses: (6 things)
palpitations, arrhythmias, diarrhoea, insomnia, tremor, weight loss
… and … are both used to treat hyperthyroidism
carbimazole and propylthiouracil
Carbimazole
used to treat …
it is a …-drug, after absorption it is converted to the … form, methimazole which prevents peroxidase iodinating the tyrosine residues on thyroglobulin, hence reduing the production of the thyroid hormones T3 and T4
Hyperthyroidism
pro-drug
converted to active form after absorption
Carbimazole
oral bioavailability?
protein binding?
metabolism?
half-life?
excretion?
standard maintenance dose ?
oral bioavailability - >90%
protein binding - 85%
metabolism - rapidly metabolized to methimazole
half-life - 6.4 hours (methimazole)
excretion - 90% excreted in urine as metabolites
standard maintenance dose - 5-15mg/day
Carbimazole - adverse effects
.. and … are common which can often be treated with …
the most serious rare side effect is … and …. Also is …
rashes and pruritus are common - use antihistamines
side effect - serious - neutropenia and agranulocytosis
also is teratogenic (can cause abnormal fetal development)
Propylthiouracil
oral bioavailability?
protein binding?
metabolism?
half-life?
excretion?
standard maintenance dose ?
oral bioavailability - 80-95%
protein binding - 70%
metabolism - 90% hepatic glucoronidation
half-life - 2 hours
excretion - renal
standard maintenance dose - 50-150mg / day
Propylthiouracil adverse effects
… and … are common which can be treated with …
notable side effects include a risk of … and risk of serious … injury, including failure and …
rashes and pruritus are common which can be treated with …
notable side effects include a risk of agranulocytosis and risk of serious liver injury, including failure and death
Chernobyl nuclear accident - lots of radioactive … released
iodine
