Thyroid Flashcards
how is thyroxine T4 produced ?
TSH controls uptake of Iodide into thyroid follicular cell
Iodide converted to Iodine
Tyrosine residues iodinated (blocked by
thionamides)
Iodotyrosines join to form thyroxine - MIT, DIT. TIT, rTIT
iodide uptake from blood into thyroid follicular cells is inhibited by what?
blocked by perchlorate
outline the microscopic structure of the thyroid gland?
The functional unit is called a ‘Thyroid follicle’:
Which is lined with Thyroid follicular cells (and occasionally parafollicular cells)
The Lumen consists of Colloid
iodide enters the thyroid follicular cells from blood how?
how is it carried into colloid?
at which point is iodide converted to iodine?
via the NAI- ; sodium iodide symporter/transporter
2 sodiums and 1 iodide are transported into the tfc at the same time.
colloid - enters via transporter called PENDRIN. 2Cl- into tfc for 1 I- into colloid.
what enzyme catalyses the following I- –> I2
Thyroid peroxidase
which membrane transporter encourages the uptake of iodide?
NAK transporter
how is thyroxine T4 made?
what different subsets of products can be made on the way? including T3?
I2, iodine is uptaken by Thyroglobulin :
Iodination of tyrosine residues on the thyroglobulin molecule with just 1 iodine -> Monoiodotyrosine
Iodination with 2 iodine -> diiodotyrosine
Triiodothyronine T3 = MIT + DIT
Thyroxinee T4 = DIT + DIT
where is thyroglobulin made?
thryoid follicular cells
What is the higher regulation of t4 production
Hypothal releases TRH
Anterior Pitiutary releases TSH
TSH stimulates absorption of thyroglobulin from colloid then process starts
what is the negative feedback loop of t4?
inhibits BOTH hypothalamus AND anterior pituitary from hormone production.
how is the iodination of Tyrosine residues regulated?
blocked by thionamides
what happens at the conclusion of t4 production?
stored in thyroid.
packed in eendosomes and uptaken into TFC by pinocytosis.
endosome fuses with lysosome to cause separation of t3 and t4
t4 and t3 can then be taken up into capillary blood - when tsh stimulates
what happens at the conclusion of t4 production?
stored in thyroid.
packed in eendosomes and uptaken into TFC by pinocytosis.
endosome fuses with lysosome to cause separation of t3 and t4
t4 and t3 can then be taken up into capillary blood
what happens with t3/4 at target cell?
t4 gets converted into t3
enter nucleus
bind to thyroid hormone receptor there
starts transcription for mrna to promote thyroid hormone response; increasing metabolic rate, growth etc.
what are the methods of Thyroid Hormone Transport?
fT4 - 0.03% -> Active
- subsequent conversion to fT3, reverseT3
TBG T4 75% thyroxine binding globulin
Thyroxine-binding pre-albumin-T4 (TBPA) 20%
Albumin-T4 5%
All must be converted to fT4 before conversion to fT3 for use
list some causes of hypothyroidism?
- Hashimoto’s disease - autoimmune
- Atrophic
- Post Graves’ disease - RAI, surgery, natural history or thionamides.
Post thyroiditis
Drugs (amiodarone and lithium)
Thyroid agenesis or dysgenesis
Iodide deficiency and dyshormonogenesis
Secondary hypothyroidism, pituitary disease (TSH no utility)
Peripheral thyroid hormone resistance
give symptoms of hypothyroidism involving the different systems;
○ Metabolic rate - slowed ○ Cardiovascular (e.g. bradycardia) ○ GI (e.g. constipation) ○ Respiratory (e.g. laboured breathing) ○ Reproductive (e.g. oligomenorrhoea) ○ Others (e.g. pituitary symptoms) ○ Weight gain with decreased resting energy expenditure and poor appetite
○ Cold and dry hands, feels cold
○ Hyponatraemia
○ Normocytic anaemia unless pernicious anaemia
goitre
Myxoedema
- altered mental state: ‘trouble thinking’
- very low Body temperature
- Swelling of face n eyes
- precipitating health event eg Infection, stroke etc
- may have forgotten to take anti-thyroid meds for some days
ivx for hypothyroid of varying causes?
○ High TSH + Low T4 in primary hypothyroidism
○ Thyroid peroxidase TPO autoantibodies (suggests autoimmune hypothyroidism - eg Hashimotos) also graves
○ Think of other autoimmune conditions that the patient may also have (e.g. pernicious anaemia, coeliac disease, Addison’s disease)
ivx for hypothyroid of varying causes?
○ High TSH + Low T4 in primary hypothyroidism
○ Thyroid peroxidase TPO autoantibodies (suggests autoimmune hypothyroidism)
○ Think of other autoimmune conditions that the patient may also have (e.g. pernicious anaemia, coeliac disease, Addison’s disease)
name the benefit of giving too much t4 or giving t3 instead of t4?
NO EVIDENCE BASE
Too much t4 -> osteopaenia and AF
