Week 9 Thyroid gland Flashcards
thyroid hormone examples:
T3 and T4
T4: Thyroxine
T3: tri-iodothyronine
how are T3 and T4 made?
Tyrosine is iodinated to become T3 and T4.
Thyroid hormone functions
- thermogenesis in brown adipose tissue (BAT)
- Basal metabolic rate
- growth development
- active mental processes
HPT system: hypothalamus-pituitary-thyroid system
Hypothalamus: Thyrotrophin releasing hormone (TRH)
Pituitary: Thyroid stimulating hormone (TSH)
Thyroid: releases T3 and T4
T3 and T4 has -ve feedback loop to Hypothalamus and pituitary.
T3 and T4 production ratio
Thyroid produces much more T4 than T3, T4:T3 is 14:1
The compartments of Thyroid Follicle and C cell
Thyroid follicle:
- Inner compartment: colloid (glue-like)
- outer layers: thyroid epithelial cells and basement membrane
C cell: parafollicular
What is the function of the colloid
The colloid makes T3 and T4!!
What is the function of the C cell? (hint: c)
C cell produces calcitonin. (Very close to parathyroid!!!)
Calcitonin is made to reduce osteoclast activity and bone resorption.
Thyroid hormone synthesis steps
- Iodine is pumped from plasma into the colloid.
- middle layer thyroid epithelial cells produces many thyroglobulin
- The enzyme TPO with H2O2 can iodinate the tyrosine residues bound on thyroglobulin.
- The colloid is reabsorbed into the epithelial cells.
- Colloid undergoes proteolysis and degraded.
- T3 and T4 are released from the colloid.
What stimulates the release of T3 and T4 from the thyroid follicles?
TSH, TSH can stimulate Ca2+ influx which leads to secretion of T3/T4.
What facilitates the process of iodinating tyrosine residues
the enzyme TPO and H2O2
In what forms do Thyroid Hormones exist in circulation?
They are 99.5% bound to proteins like thyroxine binding globulins and albumin…
They ARE INACTIVE.
What happens to T3/T4 when they get into cells?
- T4 gets converted to T3 through deiodinase 1/3
- T4 also gets converted to reverseT3 (rT3 - which is inactive) through deiodinase 1/2.
- T3 will bind to nuclear T3 receptors
-»» changes
Where does the majority of T3 production happen?
In liver, kidney cells, from the conversion of T4 to T3.
Common causes of hyperthyroidism:
- Graves Disease
- Multi-nodular goitre
- single toxic nodule
Graves Disease cause
Stimulated by antibodies to the TSH receptor
Graves Disease will lead to what symptoms?
Antibodies will stimulate T3 and T4 production.
Large smooth goitre
ophthalmopathy
What’s a common imaging technique used in observing the thyroid gland
Radio-isotope uptake, technitium
ophthalmopathy
TSH will stimulate the retro-orbital tissue which also has TSH receptor.
1. stimulation of fibroblasts
stimulate adipogeneis
stimulate ECM production
2. swelling of tissue behind the eye (lipid and water retention)
Treatments of Graves Disease
- Carbimazole
- Radioiodine
- Subtotal/total thyroidectomy
- Beta blockers
Carbimazole effect
- It is used to treat Graves disease
- It can inhibit TPO activity, which involved in T3/T4 synthesis.
- Decrease TSH receptor antibodies.
Radioiodine effect
Used to treat Graves Disease:
Functions as negative feedback loop to hypothalamus and pituitary.
Radioiodine complication
It could lead to hypothyroidism.
The negative feedback also doesn’t affect TSH receptor on ophthalmopathy, may worsen it.
What can treat ophthalmopathy?
Steroids, immunosuppression, which can reduce inflammation.
What does multi-nodular goitre do?
This is the patches of autonomous tissue that releases T3/T4 hormones.
They also reduce growth of other parts of the thyroid gland.
What is the usual treatment of multi-nodular goitre?
Radioiodine: iodine is taken up by thyroid cells, radiation will kill thyroid tissues.
As it directly suppresses the thyroid tissue, it won’t have a big issue with hypothyroidism
Thyroiditis stages and need treatment?
Hyperthyroidism -> hypothyroidism due to follicule damage -> euthyroid (the thyroid has come back to normal)
Weight in hypo/hyperthyroidism?
Weight loss in hyperthyroidism
and gain in hypothyroidism.
This occurs probably because thyroid hormones have control over metabolic rate and thermogenesis…
Hypothyroidism causes
Most common cause: Hashimoto’s thyroiditis
Less common causes: Hypopituitarism (TSH dficiency), iodine deficiency, congenital…
Mechanism of Hashimoto’s thyroiditis
There are autoimmune antibodies that attack the thyroid gland that makes it underactive permanently. (Hereditary)
TSH levels may be high due to underactive thyroid gland and low T3/4.
Treatments of hypothyroidism
- oral T4, to normalise TSH and T3 (increase T3 and reduce TSH)
- some patients may require more direct T3 + T4 doses.
What test measures thyroid hormone levels in thyroid disorders?
Immunoassays
When is competitive immunoassay used?
Used for small molecules like thyroid/steroid hormones, drugs.
How is competitive immunoassay done:
- limited antibodies stuck on the wall
- labelled analyte and sample that will competitively bind to antibodies
- the more sample, the less labelled analyte. Inversely proportional to sample concentration.
When is immunometric assay done?
For large molecules, peptide hormones (TSH, ACTH..) , proteins (BNP, troponin).
What is tested in hyperthyroidism?
TSH receptor antibodies (they stimulate T3/4 production in the thyroid gland)
How is immunometric immunoassay done:
- excess antibodies (limitless)
- The hormone will bind to the antibody
- labelled antibodies will also bind to the hormone, but on another epitope
- The stronger intensity, the more hormone concentration. Directly proportional
What is tested in hypothyroidism
Anti-TPO antibodies (Autoimmune antibodies that attack the thyroid gland to make it underactive)
Hypothyroidism biochemistry and cause
Low T3/T4 and high TSH: primary
Low T3/T4 normal-low TSH: hypopituitarism
Hyperthyroidism biochemistry and cause
very low TSH: primary
Pituitary tumour (secondary): very rare, high TSH
Sub-clinical hypothyroidism test
TSH high sensitivity:
slight decrease in free T4: large increase in TSH
Sub clinical hyperthyroidism test
slight increase in free T4, large decrease in TSH.
How can thyroidal tests be affected?
Fluctuating TSH and T3/4 levels due to:
- intercurrent illness.
Stress, illness, malnutrition and thyroid hormones
- can all negatively regulate the HPT axis
- negatively regulate the nuclear T3 receptor, and inhibit deiodinase 1/3 that’s used for T4 conversion to T3.
low TSH in a clinical setting
more likely to be non-thyroidal cause than hyperthyroidism
raised TSH in a clinical setting
could be from recovery from illness.
