The thyroid gland Flashcards
Which nerve runs close to the thyroid gland and supplies the vocal chords?
left recurrent laryngeal nerve
see diagram 3-5/33
Describe the embryology of the thyroid gland.
Midline outpouching from floor of pharynx (originates from base of tongue)
Development of thyroglossal duct
Divides into 2 lobes
Duct disappears leaving foramen caecum
Final position by week 7
Thyroid gland then develops
(see diagram 6-7/33)
Describe the action of TSH on the follicular cell.
- TSH arrives through systemic circulation
- TSH binds to the TSH receptor on the follicular cell
- Na+ and I- arrive, and enter through the NA+-I- co-transporter (I- goes into the follicular cell to be transported into the colloid)
- I- are oxidised (iodination)
- TSH binding produces thyroglobulin (TG)
TG is a protein - a pro-hormone
TSH stimulation of TSH-R creates TPO (an enzyme) which goes to the colloid
TPO + H2O2 acts as an enzyme for the reaction of iodine + TG -> MIT + DIT
DIT + MIT ( coupling reaction ) also using TPO as enzyme = T3 + T4
T3 + T4 bind to TG to enter back into follicular cell, they are separated by TG by lysosomes and released into bloodstream
Describe the production of T3 and T4 via the mechanism of TSH on the follicular cell.
- TSH arrives through systemic circulation
- TSH binds to the TSH receptor on the follicular cell
- Na+ and I- arrive, and enter through the NA+-I- co-transporter (I- goes into the follicular cell to be transported into the colloid)
- I- are oxidised (iodination)
- TSH binding produces thyroglobulin (TG)
TG is a protein - a pro-hormone
- TSH stimulation of TSH-R activates an enzyme, TPO (thyroperoxidase) [this enzyme is important in the production of thyroid hormone]
- TPO + H2O2 catalyses iodination reactions to produce MIT (monoiodothyronine) and DIT (diiodothyronine)
- these products join together to give you thyroid hormone
- T3 + T4 are still bound to TG, enters the cell; in the lysosomes the protein bonds are broken down and thyroid hormone enters the bloodstream
(see diagram 8/33)
What is the active thyroid hormone?
T3
What enables TG to be iodinated (in terms of structure)?
TG has thyrosine residues (which have an aromatic ring)
there are around 100 residues
of these 100, ~20 can be iodinated
(see diagram 9/33)
What is the main hormone product of the thyroid gland?
T4
By which process can you turn T4 into T3?
Deiodination
Is T3 the bioactive form?
yes
Where is T4 turned into T3?
In target tissues
What would happen i you deiodinated T4 in a different position?
produce reverse T3 (this is inactive)
Which enzyme enables the conversion of tetraiodothyronine (thyroxine/T4) into its more active metabolite triiodothyronine (T3)?
deiodinase enzyme
What is circulating T3 composed of?
80% from deiodination of T4
20% from direct thyroidal secretion
What is the role of T3
provides almost all of the thyroid hormone activity in target cells
How are T4 and T3 transported in blood?
bound to plasma proteins
Which plasma proteins are T3 and T4 bound to?
thyroid-binding globulin (TBG) - 70~80%
albumin (10~15%)
prealbumin (transthyretin)
only 0.05% of T4 and 0.5% of T3 is unbound (bioactive components)
Describe the mechanism in which T3 and T4 can effect gene expression.
they enter the bloodstream from the thyroid gland and act on target tissues
enter cells through its respective receptors
T4 is deiodinated to T3
T3 enters nucleus with the thyroid responsive element
when T3 binds to thyroid hormone receptor, it can alter gene expression by activating or repressing gene transcription
What is thryoid hormone important for?
essential for fetal growth and development
especially for the brain and CNS
- ↑Basal metabolic rate
- Protein, carbohydrate & fat metabolism
- Potentiate actions of catecholamines (e.g. tachycardia, lipolysis)
- Effects on the GI, CNS, Reproductive systems
What is cretinism?
when a baby is born without either a thyroid gland or any functioning thyroid hormones
looks drowsy, sleepy
this is quite rare now
What is the heel-prick test?
on day 5 of life
drops of blood removed from heel of feet
compulsory in UK
measurement of TSH
to see whether they have an underactive thyroid
if TSH levels are high, suggest that baby might have congenital hypothyroidism
- -> if so, can be treated with thryoid hormone replacement
- -> requires lifelong treatment
What is the half lives of T4 and T3?
T4: 7-9 days
T3: 2 days
How does thyroid hormone effect growth, CNS, BMS, metabolism, cardiovascular?
Thyroid hormone binds nuclear receptor -> synthesis of new proteins
Growth: Growth formation, Bone maturation
CNS: maturation of CNS
BMS: ↑Na+/K+ ATPase, ↑O2 consumption, ↑Heat production, ↑BMR
Metabolism: ↑glucose absorption, ↑gylcogenolysis, Gluconeogenesis, ↑lipolysis,
↑protein synthesis & degradation
Cardiovascular: ↑cardiac output
Are thyroid disorders more common in men or women, or the same?
Women (4:1)
Describe the hypothalamo-pituitary-thyroid axis.
TRH produced within the hypothalamus
TRH acts on thyrotrophin cells of the anterior pituitary to stimulate the release of TSH
TSH enters systemic circulation and arrives at thyroid gland
production of T3 and T4
but this has negative feedback! (homeostasis)
Is an overactive thryoid gland or an underactive thyroid gland more common?
the same
overactive = hyperthyroidism underactive = hypothyroidism
What impact can somatostatin have on the production of TSH?
It can inhibit TSH production
What impact can iodide have on the production of TSH?
in large quantities, it can inhibit the production of T3 and T4
if someone has hyperthyroidism, could give them a large amount of potassium iodide to stop any more thyroid hormone being produced from the thyroid
—> this is the Wolff-Chaikoff effect
What is primary hypothyroidism?
Autoimmune damage to the thyroid
- Thyroxine levels decline
- TSH levels climb
Why are the most common forms of autoimmune thyroid disease?
Hashimoto’s thyroiditis and Graves’ disease.
• Hashimoto’s is usually associated with hypothyroidism
- Graves’ disease tends to cause hyperthyroidism but sometimes can also cause hypothyroidism
you can also get hypothyroidism as a result of a thyroidectomy
What are the symptoms and signs of hypothyroidism?
- Deepening voice
- Depression and tiredness
- Cold intolerance
- Weight gain with reduced appetite
- Constipation
- Bradycardia
- Eventual myxoedema coma
- fatigue, memory impairment, depression
- swollen face, swelling of the eye socket, rough, deep or hoarse voice
- weight gain, constipation
- dry, rough skin, paresthesia, muscle cramps
- shaggy hair, hair loss
- enlarged thyroid gland
- slowed heart rate, weakness
- diminished potency and fertility, low sexual desire, cycle disorders
What is the proposed mechanism of action of levothyroxine?
Normally, you would get T4, produced from the thyroid gland, which is deiodinated to give the active hormone T3.
–
Levothyroxine is almost identical to T4 and can be deiodinated to get T3
What is the common dosing for Levothyroxine?
Adjusted according to TSH (aim to get into normal range)
Common dose 100 micrograms
Most commonly administered orally
What are the potential complications of using Levothyroxine?
Minor:
weight loss
headache
Major:
heart attack
rapid HR
What is combine thyroid hormone replacement usually composed of?
T4 = prohormone, converted by deiodinase action to T3
Combination T4 / T3 – some reported improvement in wellbeing
What is Liothyronine used for?
It is like T3; however, it is an expensive drug compared to levothyroxine and there is no evidence to show that it works better.
What is hyperthyroidism?
Thyroid makes too much thyroxine
• Thyroxine levels rise
• TSH levels drop
What is hyperthyroidism?
Thyroid makes too much thyroxine
• Thyroxine levels rise
• TSH levels drop
What can cause hyperthyroidism?
- Graves’ disease – whole gland smoothly enlarged and whole gland overactive
- Toxic multinodular goitre
- Solitary toxic nodule
What is Graves’ disease?
Autoimmune disease
Antibodies bind to and stimulate TSH receptor in the thyroid
• Smooth goitre
Other antibodies bind to muscles behind eye
• Exophthalmos
(see diagram 28-29/33)
What are the symptoms and signs of hyperthyroidism?
- Heat intolerance
- Weight loss with increased appetite
- Myopathy
- Mood swings
- Diarrhoea
- Tremor of hands
- Palpitations
- Sore eyes, goitre
- nervousness, irritability, insomnia, depression
- weight loss, strong feeling of hunger, diarrhoea
- fragile fingernails, shaking hands
- warm, moist skin, increased body temperature
- broken hair, hair loss
- enlarged thyroid gland
- increased heart rate, arrhythmia, high b.p.
- muscle cramps, muscle weakness
(- cycle disorders)
