PBL 5 Flashcards
(36 cards)
What are the two thyroid hormones
Triiodothyronine (T₃) and Thyroxine (T₄)
what do the thyroid hormones do
regulate metabolism
what is the main thyroid hormone in the blood
T₄ is the main form in the blood (ratio T₄:T₃ is 20:1)
How is T4 converted into to T3
T₄ is converted into active T₃ within cells by deiodinases
which is more potent T3 or T4
T₃ is 4x more potent
what is thyroid hormone in the blood bound to
Most thyroid hormone in blood is protein bound
mainly Thyroxine-binding globulin TBG
free thyroid hormone is…
biologically active
How are thyroid hormones produced
Iodide trapping: Iodide (I-)moves
into follicular cell through Na+/I-
symporter
I- moves into colloid
I- is oxidised to Iodine (I) by thyroid peroxidase (TPO)
Meanwhile, thyroglobulin is
synthesised on rough ER and is exocytosed into colloid
Iodine is reactive & iodinates
tyrosyl residues of thyroglobulin (catalysed by TPO) to form MIT
and DIT
The tyrosyl residues pair together
Iodinated thyroglobulin is
endocytosed back into cell
Lysosomes fuse and cause
proteolysis, resulting in formation of T3 & T4
Thyroid hormones are then
released into blood
describe then hypothalamic pituitary thyroid axis
Hypothalamus secretes
thyrotropin-releasing
hormone (TRH)
TRH stimulates the Anterior
pituitary to release thyroid
stimulating hormone (TSH)
TSH stimulates T3 and T4
production from the thyroid
gland
- T3 and T4 loop back and inhibit TRH and TSH when the concentration of T3 and T4 get too high
Negative feedback loop
what is the difference between hyperthyroidism and hypothyroidisms
Hyperthyroidism
- T3 and T4 is risen
- TSH decreased
hypothyroidism
- T3 and T4 decreases
- TSH increases
deiodinase activity varies…
Deiodinase activity varies from tissue to tissue
describe how deiodinase activity varies in different tissues
Deiodinase 1 = liver & kidney activates T4 🡪 T3
Deiodinase 2 = brain, heart, skeletal muscle activates T4 🡪 T3
Deiodinase 3 = fetal tissue, brain neurones inactivates T3&4
describe the T4 and D2 hormones
If T4 levels fall, D2 is upregulated. Elevated levels of T4 will downregulate D2, to protect brain tissue from excess thyroid
hormone.
What is the role of T4 and T3
Increases basal metabolic rate
- Increased heat production
Increased triglyceride breakdown, fatty acid
oxidation and cholesterol
- Hypercholerstrolaemia is an indication of
hypothyroidism
Increase insulin dependent entry of glucose into
cells via GLUT4 in the muscles
increase glycogen breakdown and increase gluconeogenesis in the hepatocytes
Increases cardiac output
- Increased contractility, heart rate, and and promotes
vasodilation
Stabilises GI motility and tone
- Imbalances in thyroxine levels causes either diarrhoea
(too much) or constipation (too little)
Ensures normal reproductive physiology
- Imbalances are associated with reduced reproductive
function
What is the role of T4 and T3 in children
Essential for growth in children
- Congenital hypothyroidism is tested for in
heel prick test
- Cretinism
Essential for brain development
- Too much thyroid hormone causes anxiety
and nervousness
- Too little thyroid hormone causes sluggish
thinking
- Plays a role in foetal and neonatal brain
development
what are the causes of hypothyroidism
- iodine deficiency - most commenst cause
- Hashimoto’s thyroiditis
- post-partum thyroiditis
- pituitary disease
- congenital hypothyroidism - cretinism
- lithium or amiodarone
what is hashimotors thyroditisi
Autoimmune condition characterised by lymphocytic infiltration of
thyroid gland and anti-TPO and anti-Tg antibodies
describe the epidemiology of Hashimoto’s thyroiditis
Commonest in the UK
Commonly affects women
Type 2/4 hypersensitivity
what are the symptoms of hyothyrodisim
Weight gain, obesity – with a low appetite
Cold intolerance, hypothermia
Depressed/low mood/tired/lethargic
Constipation
Dementia
what are the signs of hypothyroidism
Bradycardic
Slow relaxing reflexes
Hoarse voice
Ataxia
Thin and brittle hair
Loss of lateral one third of eyebrow
Cold hands
Ileus (paralytic obstruction of bowels)
How do you distinguish between primary and secondary diseases
Interpreting TFTs:
- Check T4 first to determine if hyper or hypo
- Then check TSH to see if 1o or 2o disease
Primary diseases originate in the thyroid gland
- TFTs will go in “opposite directions” i.e. Primary
hypothyroidism has reduced T4 and high TSH
Secondary diseases originate from higher up the
HPT axis
- TFTs will go in the “same direction” i.e. secondary
hypothyroidism has low TSH and subsequently low T4
All to do with negative feedback
what is the management of hypothyroidism
Levothyroxine
- Doses are tapered up in patients with cardiac
issues/severe hypothyroidism
- Doses are dependent on patients body weight
- Measure cortisol level
- Treatment is life long
- start on a low dose and work up as it can cause angina and an MI
Treat underlying cause (e.g. surgery for pituitary
adenoma)
TFTs three months after administration
- Yearly follow ups after this
what does a decrease in cortisol cause
Addison’s presents with similar symptoms
Addison’s is an autoimmune condition
Cortisol is important to test before administration to
avoid an addisonian crisis
what does a decrease in B12 cause
Symptoms
Pernicious anaemia is autoimmune
Hypothyroidism can cause B12 deficiency
