4 - Hypothyroidism Flashcards
(31 cards)
What does the thyroid gland secrete?
T3 = Tri-iodothyronine T4 = Tetraiodothyronine (Thyroxine)
What hormone stimulates the thyroid to release T3/T4 and where does it come from?
TSH = Thyroid-Stimulating Hormone
[thryotropin]
- from the pituitary
What is T4 and how is it made useful in the body?
It is a pro hormone
- converted by deiodinase enzyme into the more active metabolite triiodothyronine (T3)
Where percentage of circulating T3 comes from the thyroid?
20% = from direct thyroidal secretion 80% = from deiodonation of T4
What does T3 do in a general sense?
T3
- provides almost all the thyroid hormone activity in target cells
- controls basal metabolic rate
Explain the mechanism TSH’s effect on the thyroid
BLOOD SIDE = BASAL MEMBRANE
COLLOID SIDE = APICAL MEMBRANE
- TSH binds to thyrotropin receptors on serosal/basal membrane of follicular cell
- Iodide is pumped into the follicular cells from the blood via iodide pumps
- Iodide is then pumped into the colloid via Pendrin pumps
- TSH also stimulates the nucleus and Thyroglobulin is synthesised
- Thyroglobulin is also moved into the colloid but stays associated with the apical membrane
- TSH also stimulates Thyroid Peroxidase (TPO) enzyme
- TPO converts iodide in colloid into reactive iodine in presence of hydrogen peroxide
- Tyrosyl residues in thyroglobulin are iodinated in one or two position
- Monoiodothyronine (MIT) and Diiodothyronine (DIT) are formed
- TPO allows coupling reactions
- T3 and T4 are formed
- Colloid stores iodothyronines
- TSH stimulates lysosomes to move to apical membrane
- TSH stimulates the apical membrane to uptake colloid
- Internalised colloid fuses with lysosome
- Liberates T3 and T4
- T3 and T4 move out into blood
Explain the cell arrangement in the thyroid
Follicles
- follicular cells surrounding a collection of colloid
- colloid is a proteinaceous substance
Which hormone produced by the thyroid is active?
T3 = triiodothyronine
How can you tell when the thyroid is very active?
There are more follicular cells in each follicle
Which hormones are part of the thyroid gland axis?
Hypothalamus
- TRH (Thyrotropin-Releasing Hormone)
Anterior Pituitary
- TSH (Thyrotropin/Thyroid-Stimulating Hormone)
Thyroid
- T3 (Triiodothyronine)
- T4 (Thyroxine/Tetraiodothyronine)
Where does negative feedback exist in the thyroid gland axis?
T4/T3 have negative feedback on TSH
TSH has negative feedback on TRH
How long will stored iodothyronines in colloid last in no more hormone is being synthesised?
Approximately a month
How can you differentiate between Primary and Secondary Hypothyroidism?
Primary
- High TRH, High TSH, Low T4
Secondary (much less common)
- Generally low TSH
Explain Primary Hypothyroidism and its cause
- Thyroid gland itself not working
- e.g. due Autoimmune damage to the thyroid gland, Removal of thyroid, radioactive iodine damage
- High TSH
- Low T4
What’s another name for Primary Hypothyroidism?
Myxoedema
What are the signs and symptoms of Primary Hypothyroidism?
- weight gain with reduced appetite
- cold intolerance
- tiredness
- depression
- deepening voice
- constipation
- bradycardia
- thick tongue
- slow speech
- myxoedema coma (if it progresses far enough)
Explain Secondary Hypothyroidism and its cause
- Pituitary or Hypothalamus not working
How does T3 work in the body?
- T4 and T3 enter a cell
- T4 deiodinated to T3
- T3 enters nucleus
- T3 binds to heterodimer receptor (Thyroid Hormone Receptor and Retinoid X Receptor)
- Binds to certain area called the ‘thyroid response element’ which is the DNA part of the receptor
- Alters gene expression
What is the ideal treatment plan given to someone with Primary Hypothyroidism?
Thyroxine (T4)
- thyroxine or salt of thyroxine (e.g. thyroxine sodium)
- take it everyday
- dose decided when TSH starts to go down and is in the right reference range
- oral administration
Liothyronine sodium (T3)
- less commonly used
- because people can convert T4 to T3
- more expensive
What is the ideal treatment plan given to someone with Secondary Hypothyroidism?
Levothyroxine
- Synthetic thyroxine
- Oral administration
- TSH low due to APG failure so can’t use TSH level to guide dose
- Aim for fT4 (free T4) in middle of reference range
Explain Secondary Hypothyroidism and its cause
- Problem with Anterior Pituitary Gland usually
- e.g. due to pituitary tumour, post-pit surgery or radiotherapy
When would you give as treatment to someone in Myxoedema coma?
INITIALLY
- I.V. Liothyronine (Synthetic T3)
- Faster onset of action than T4
- May not be absorbing/digesting tablets well
THEREAFTER
- oral administration as soon as possible
When would give Combined Thyroid Hormone Replacement?
- Combined T4/T3
- Rarely prescribed
- Some reports about improvement in well-being
- No real evidence to support T3 use
- Complicated by ‘toxicity’ symptoms because T3 is so biologically active, can give symptoms of overactive thyroid, suppresses TSH
- Very hard to get T3 dose correct
What does fT3 and fT4 stand for?
Free T3 and Free T4
= unbound
= only small % is free and biologically active
= fT4 is what is measure in blood tests
