Thyroid Flashcards
Name 2 reasons why the thyroid gland is so vascularised
- needs to get iodine out of the blood
- secretes hormones into the blood
Name the 2 membranes lining the thyroid follicles
Basal membrane (faces out to capillaries) Apical membrane (faces in towards lumen)
What is stored in the lumen of thyroid follicles / colloid
Thyroglobulin
Other name for T4?
Thyroxine
Which thyroid hormone is the MOST inactive
Reverse T3 (reverse triiodothyronine)
Which thyroid hormone binds more readily to plasma proteins?
T4 - thyroxine
Which plasma protein does T4 bind to?
Thyroxine binding globulin (TBG)
There are 2 reservoir mechanisms for thyroid hormones which prolong their effect and means drugs take a while to take effect. What are they?
- stores or thyroglobulin in colloid of follicles
- 99% of T4 binds to TBG
Explain the role of the TPO enzyme
Once iodide enters the cell through the sodium potassium pump, it then reacts with TPO which takes another electron away, making it more negatively charged. This increases its reactivity
Iodide reacts with thyroglobulin to form which possible compounds?
MIT - mono-iodotyrosine
DIT - do-iodotyrosine
A condensation reaction between which molecules creates the thyroid hormones?
MIT and DIT (different combinations create the different hormones)
Why is iodide brought into the cell via a sodium potassium pump?
Because the concentration in the cell is higher than in the blood, therefore moving against its concentration gradient. This process requires energy
MIT + DIT =?
T3 or rT3 (depending on order)
DIT + DIT = ?
T4
How does t4 or T3 move from the colloid where it was produced into the cell?
Through endocytosis
Once in the cell, thyroglobulin with T3 or T4 attached fuses with which molecule?
A lysosome
What happens with the lysosome fuses with thyroglobulin with T4 or T3 attached?
It digests / breaks down the thyroglobulin, leaving just the hormone, which is then released into circulation
Around 90% of thyroid hormones secreted are in which form?
T4
What impact would declined liver function have on thyroid hormones?
Inability to effectively convert T4 into T3, meaning less activity
What hormone is released from the hypothalamus that acts on the anterior pituitary in relation to thyroid hormones?
TRH - thyrotrophin releasing hormone
The anterior pituitary releases which hormone that acts on the thyroid gland?
Thyroid stimulating hormone (TSH)
What effect does TSH have on the thyroid gland?
Promotes growth of the gland (tropic effect)
Promotes the release of hormones
Describe the negative feedback loop of thyroid hormones
T3 and T4 feedback to the hypothalamus and anterior pituitary which shuts of release of TRH / TSH
Describe the effect of thyroid hormones on metabolism
Thyroid hormones increase the oxygen consumption of cells, resulting in heat production. This increases the basal metabolic rate (BMR)
How does excess thyroid hormones cause muscle weakness
Has a catabolic effect on proteins and causes muscle breakdown
How does thyroid hormone deficiency cause muscle weakness?
Not enough metabolism / energy production
Other than skeletal muscle development, the growth of which other area of the body is dependent on normal thyroid hormone levels?
The CNS. Thyroid hormones are essential for CNS maturation during early years and maintenance of brain function in adults
Why are thyroid conditions increased during pregnancy?
Due to high metabolic demand
Define euthyroid
Normal levels of free thyroid hormones
Other than gland failure, list some causes of hypothyroidism
- secondary to deficiencies of TSH / TRH
- low dietary iodine intake
Explain why hypothyroidism results in increased sensitivity to the cold
Because the body is not producing enough heat
Excessive weight gain is a symptom of hypothyroidism that can be associated with which other symptom?
Reduced BMR
Slow reflexes, slow speech and slow pulse are symptoms of which condition?
Hypothyroidism
Define myxoedema
Oedema around the eyes and feet
Associated with hypothyroidism
Describe the consequences of congenital hypothyroidism
Underdeveloped CNS, small stature, low metabolic rate
- stunted growth in all areas
Name synthetic T4
Levothyroxine
Name synthetic T3
Liothyronine
In which case would you use liothyronine over levothyroxine?
Liothyronine (synthetic T3) is used when a faster response is needed, whereas levothyroxine (T4) is used more long term / for sustained therapy
Name the autoimmune condition associated with hypothyroidism
Hashimoto’s Thyroiditis
Explain how Hashimoto’s thyroiditis decreases the production of thyroid hormones
The autoimmune condition promotes antibodies for TPO or thyroglobulin. A reduction in these two molecules limits the production of thyroid hormones.
How does Hashimoto’s thyroiditis lead to goitre
A decrease in thyroid hormone release means there is no negative feedback to the hypothalamus or anterior pituitary. This means the release of TSH is increased, leading to constant growth of the thyroid gland
Graves’ disease and excess TSH or TRH are potential causes of….
Hyperthyroidism
Thyroid hormone’s effects on catecholamines causes which symptoms of hyperthyroidism?
Excessively alert, irritable, anxious, etc
List at least 3 symptoms of hyperthyroidism
- elevated BMR
- weight loss without trying (coupled with increased appetite)
- muscle weakness
- heart palpitations
Exopthalmos (protrusion of the eyeballs) is common in which condition?
Grave’s disease
Surgical removal of a portion of the gland is a treatment option for which condition
Hyperthyroidism
Why is a large dose of potassium iodide sometimes used before surgery?
It shrinks the gland and temporarily inhibits function (used in hyperthyroidism)
Explain how radioactive iodine can be used as hyperthyroidism treatment
The beta rays from the I-131 isotope cause local tissue destruction
Carbimazole, a prodrug to methimazole, is used to treat which condition?
Hyperthyroidism
Explain the MOA of carbimazole and methimazole
Inhibit thyroperoxidase (TPO) which prevents the production of thyroid hormones.
Explain why hyperthyroid drugs take a few weeks / months to start working
Because the body has stores of thyroglobulin in the colloid as well as T4 bound to TBG. The drug is working right from day 1, but the body has to use up these stores before the effects of the drug / the effects of less thyroid hormones is seen
Neutropenia is a side effect of anti-hyperthyroid drugs. Explain this adr
Depletion of neutrophils, which increases the risk of bacterial infections
Explain why goitre occurs in hyperthyroidism
TSI (thyroid stimulating immunoglobulin) acts on TSH receptors on the gland which promotes excessive growth.
What is TSI and which auto-immune disease is it associated with?
Thyroid stimulating immunoglobulin
Associated with Grave’s disease
Explain Grave’s disease
TSI acts as an agonist on TSH receptors and increases the activity, as well as the growth, of the gland.
What percentage of thyroid hormones are bound to thyroxine binding globulin (TBG)in plasma?
99%. Because they are so lipophillic
What happens when TSH is released from the anterior pituitary?
It acts on the thyroid gland to stimulate the release of T3 and T4 into the plasma. Because it is also a trophic hormone, it also causes growth of the gland
Describe the different MOAs of primary and secondary secondary hypothyroidism.
Primary = gland failure, leading to reduced TH levels and an increase in TSH (which tries to increase levels). Increased TSH causes goitre Secondary = hypothalamus or anterior pituitary failure. Reduced TH levels and reduced TRH or TSH
Goitre is caused by …
TSH
What effect does insufficient dietary intake of iodine have on hormone levels?
Decreases T3 and T4 levels and increases TSH (meaning goitre can occur)
Name the 2 secretory cells of the thyroid Gland + what they secrete
- follicular cells - secrete T3 and T4
- C cells - secrete calcitonin
Where does thyroid hormone synthesis occur
In the colloid
Explain why a Sx of hyperthyroidism is being overly alert, anxious and emotional?
Due to increased activity of catecholamines, since thyroid hormones increase cells’ responsiveness to these molecules.
Catecholamines = adrenaline, noradrenaline and dopamine
Where is T3 and T4’s target receptor?
Located intracellularly in most cells. It binds to a nuclear bound receptor (the thyroid-response element of DNA). Once bound, gene transcription is altered which allows for production of enzymes which carry out the cellular response
Thyroid hormone causes xxx of the adrenaline receptors, causing xxxx
Proliferation
SNS like effects
Consequence of low TSH levels?
Atrophy of gland and hypo-secretion TH
Main the 3 causes of hypothyroidism (non-autoimmune)
- Failure of gland
- Secondary to TSH or TRH deficiency
- Inadequate iodine intake
Though their actions are similar, how is TSI different from TSH
TSI is not regulated by negative feedback
In which scenarios will goitre be present in hypothyroidism
- primary gland failure or iodine deficiency
These both activate the feedback system to produce more TSH to try increase TH levels
Would a hypersecretion tumour cause goitre?
No. This would activate negative feedback and shut up TSH release. Goitre only occurs when there is increased TSH (Or TSI)
Name T3
Triiodothyronine
Once the lysosome breaks T3 and T4 off, why is the iodine from MIT and DIT recycled?
Because the cell spent a lot of energy trying to get the iodine out of the blood, and it doesn’t want to waste it
Explain radio active iodide therapy.
The radioactive isotope is taken up into the thyroid gland and kills off some of the surrounding tissue. Causes hypothyroidism and some destruction of the gland.
Pneumonic to remember thyroid Sx?
Big (BMR) wedgies (weight loss or gain) Must (muscle weakness / energy levels) Hurt (heart) Gnomes (Goitre)
