patient sem 1 : Thyroid

Question 1

where is the thyroid gland?

Answer 1

the thyroid gland is found infront of the trachea and Adams apple

Question 2

how many lobes does the thyroid have ?

Answer 2

2: left and the right , some people (10-30%) have a 3rds lobe - the pyramidal lobe

Question 3

Describe the microscopic structure of the thyroid gland

Answer 3

functional units : thyroid follicles
each follicle is full of thyroid globulin which is an iodide store (essential for gland functioned for thyroid hormone)
follicles also contain follicular cells on the perimeter
and colloid glycoprotein in the centre
parafollicular C cells between the cells

Question 4

what is the function of a parofollicular c cell?

Answer 4

production and secretion of calcitonin ( responsible for calcium homeostasis)

Question 5

How is the thyroid gland regulated?

Answer 5

hypothalamus releases TRH
ant. pituitary releases TSH
thyroid gland releases Thyroid hormones (T3 and T4)

Question 6

describe the differences between t3 and t4 (thyronine hormones)

Answer 6

t3 is more active
t3 is secreted in a smaller quantity
t3 has 3 iodide molecules ,t4 has 4 
t3 is invoelt in negative feedback loop for HPT axis
t3 has a shorter half life

Question 7

what happens when there is a low body temperature

Answer 7

hypothalamus detects low body temperature, triggers release of thyroid hormone via HPT axis, leads to an increase in basal metabolic rate, heat generated
homeostasis achieved.
negative feedback brings thyroid hormone back to normal

Question 8

describe the effects of low t3 on thyroid gland

Answer 8

if there are low levels of T3, likely low TRH , stimulates pituitary thyrotropes increasing TSH levels,TSH causes enlargement of thyroid via follicular cells overactivity

Question 9

describe the effects of high t3 on thyroid gland

Answer 9

if there are high levels of T3, TRH will be low, high T3 cause thyrotropes to reduce TSH production, , reduces thyroid gland activity, less hormone produces, decreased size

Question 10

describe how TSH has an effect on the thyroid

Answer 10

TSH in blood stimulates follicular cells to produce thyronine hormones

follicular cells have cell surface receptors for TSH
(gPCR)
activates adenylate cyclase to produce cAMP

Question 11

name 4 functions of the thyroid cells

Answer 11

thyroglobulin synthesis

iodide pumping into follicular cells and follicular men

iodination by thyroid peroxidase

endocytosis,proteolysis and hormone release

Question 12

What is thyroglobulin? where is it found

Answer 12

(backbone of thyronine synthesis), found in centre of follicles

Question 13

how does iodide enter the follicular cells?

Answer 13

transported into basolateral cell membrane via sodium/iodide symporters (NIS) (is a co transporter)
co- transports NA and I- to maintain Na+ gradient which powers iodide movement
gradient maintained by Na/K+ ATPase transporter to actively transport Na out to maintain gradient

then over apical membrane into lumen via the Pendrin transporter : an ionexchanfer (cl- and iodide -) found in many body cells

once in cell, iodide oxidised to iodine

Question 14

how is thyroglobulin produced?

Answer 14

produced by the endoplasmic reticulum in the follicular cells nd exocytosed into thyroid lumen

Question 15

how are iodotryrosines formed and coupled in the thyroglobulin molecules

Answer 15

TPO adds iodide onto the backbone
addition occurs either side of the Oh molecules, max 2 iodide per backbone
backbones can join together (conjugate) tp produce t3 (3 iodides) or t4 (hormones)

Question 16

what does DIT and MIT mean?

Answer 16

di- iodotryosine

mono-iodotyrosine

Question 17

ROLE OF TPO?

Answer 17

addition of iodide to thyorogobulin backbone

conjugation and DIT and MIT

Question 18

How are T3 and t4 formed

Answer 18

DIT + DIT = T4

MIT + DIT = T3

Question 19

describe the release of T3 and T4?

Answer 19

conjugated into a huge inactive complex , lysosomal endocytosis transports back into follicular cell, proteolysis of complex releases thyroxine (t4) and triiodothyronine (T3)
excess iodide receyles into lumen to produce more hormone
T3 and T4 ready for secretion into blood

Question 20

why is T4 used as a medicine rather than t3

Answer 20

longer half life

easily converted to t3

Question 21

what is reverse t3?

Answer 21

inactive hormone, less than 1% of thyroid hormone production
t4 is easily converted to rT3

Question 22

name the four groups of thyroid anti-thyroid drugs ?]what are theorems

Answer 22

Thyronine hormones : 
levothyroxine sodium (T4) ( tablets and oral solution)

liothyronine sodium (t3) (tablets and sole iv selection)

antithyroid drugs:
carbimazole (tablets)
propylthiouricil

Question 23

How do we get thyronine hormones to target tissues?

Answer 23

thyroxine conjugates with binding proteins which are synthesised in the liver, albumin (5-10%
thyroxine binding globulin (binds 70-75%) and transthyretin (TTR) (binds 20% and takes to CNS)

Question 24

Why is the liver important in thyroid disease?

Answer 24

liver disease leads to loss of effective t4 transport

Question 25

Describe the importance of thyroxine binding globulin?

Answer 25

large circulating reservoir binds to any t4 to prevent loss in the urine

Question 26

Describe the function and half life of thyroid binding hormones

Answer 26

TBG bind T3 and T4, half life 5 days transthyretin binds T4 only half life of 2-3 days albumin binds T3 (30%) and t4 (10%) protein bound T4 and T3 20:1

Question 27

how are T3 and t4 transported into cells?

Answer 27

free (non protein bound) T3 and T4 enter cells by specific transporters (e.g. MCT8, MCT10 and OATP1c1) t3 is bio active, t4 inactive, converted toT3 by intracelluclar iodthyronine deiodinases

Question 28

what are the types iodiothyronine deiodinases ? what do they do

Answer 28

DIO1 and DIO2 converts t4 into t3 DiO1 and DIO3 converts T4 into rT3 they are selenocysteine- containing enzymes selenium accepts iodides

Question 29

where is DIO1 found | what is its major product

Answer 29

liver, kidney,muscle,thyroid | circluating T3

Question 30

where is DIO2 found | what is its major product

Answer 30

``` areas of the CNS pituitary thyrotropes intracellular T3 (important for feedback regsulation ```

Question 31

what is the importance of DIO3? | what is its major product?

Answer 31

rT3 | protective enzyme - decreases high concentrations of thyroid hormone

Question 32

describe the thyroid hormone receptor

Answer 32

produced by TR(alpha) and TR(beta) found in nucleus heterodynes with retinoid X receptor functions as a transcription factor i.e. binding to response element to increase transcription binds to TRE inhibit gene transcription when thyroid hormone not bound to it or in some cells binding decreases

Question 33

compare t3 and t4 binding affinity to TR

Answer 33

15: 1 t3: t4

Question 34

what affect does binding of T3 to the TR have on growth hormone concentrations?

Answer 34

increases them

Question 35

what affect does binding of T3 to the TR have on prolactin concentrations?

Answer 35

decrease

Question 36

what affect does binding of T3 to the TR have on concentrations of alpha and beta subunits of TSH?

Answer 36

reduce alpha and beta sub units of TSH

Question 37

what are the 5 biological actions of thyroid hormones

Answer 37

``` control of basal rate control of growth foetal development Cardiovascular effects Musculoskeletal effects ```

Question 38

what problems can arise from iodine deficiency in foetus?

Answer 38

foetus: miscarriage, stillbirth, congenital abnormalities

Question 39

what problems can arise from iodine deficiency in childhood and adolescent

Answer 39

goiter - can be subclinical impaired mental function impaired physical development

Question 40

what problems can arise from iodine deficiency in neonates

Answer 40

neonatal loiter neonatal hypothyroidism impaired mental function

Question 41

how does thyroid have cardiovascular effects?

Answer 41

``` T3 increases cardiac contraction and output heart rate oxygen supply CO2 removal from tissues INCREASED OUTPUT ``` inc of myocardial ca 2+ uptake inc expression of alpha myosin heavy chain and decrease in delta inc expression of Ryanadone receptor in SR inc metabolism thermogenesis vasodilation sensitivity to catecholamines

Question 42

how does thyroid have musculoskeletal effects?

Answer 42

T3 has a potent stimulatory effect on bone turnover inc both formation and resorption t3 inc linear bone growth after birth T3 inc rate of muscle relaxation normal skeletal muscle function requires T3