Thyroid problems

anatomy of thyroid

types of cells in the thyroid

-embryology of thyroid gland
-what does it develop from ?
-grows from which laryngeal arches for form \___ duct?

develops from ENDODERMAL DOWNGROWTH of pharynx between ant 2/3 and post 1/3 of tongue
grows from FORAMEN CAECUM
between 1st and 2nd laryngeal arches to thyroid cartilage
forming THYROGLOSSAL DUCT

where would ectopic thyroid tissue be found?
and when is it important to check for this?

sites along thyroglossal duct
need to check when removing thyroid

what 2 types of hormones does the thyroid produce?

T3, T4
calcitonin

what is the thyroid made up of, what is its structure?
what does septa carry?

series of follicles surrounded by connective tissue capsule
septa invest gland carrying blood vessels, lymph , nerve

what produces hormones in thyroid, and what are these?

FOLLICULAR CELLS\= cuboidal epithelia cells arranged in follicles
PARAFOLLICULAR CELLS\= c cells, neuroendocrine

where is hormone stored in thyroid?
how is it stimulated and then released into blood?

stores inactive hormone in lumen of follicles (colloid)
activated by follicular cells on demand
follicular cells take up colloid, activate it and pass it into bloodstream

what do T3 and T4 contain?
what is their full name?
which is converted into active?
what do they do?
how is secretion stimulated?

iodine containing low molecular weight horomones
T3\= tri-iodothyronine
T4\= thyroxine
T3 is active, T4-\>T3
regulate basal metabolic rate, growth, maturation
secretion regulated by TSH from ant pit

what particular tissue does T3/4 cause maturation of?

nerve

what is calcitonin?
what is its function?
it's the antagonist of?
what is it produced by?

polypeptide hormone
regulates blood calcium levels
antagonist of PTH
produced by parafollicular c cells

how does calcitonin regulate blood calcium levels?

lowers blood calcium
-inhibits osteoclast reabsorption of bone
-increases osteoblast activity

what regulates calcitonin?

blood calcium levels
independent of pituitary

what 2 places are c cells found in thyroid gland?
how do they stain?
what do they contain?
what do they produce?

singly in follicles or interstitium in clumps
large, pale staining
have neuroendocrine granules
calcitonin

what are the 2 arteries that supply the thyroid?

superior thyroid -ext carotid
inferior thyroid -subclavian

what are the 3 veins that drain the thyroid?

superior thyroid -int jugular
middle thyroid -int jugular
inferior thyroid -SVC/subclavian

what happens in hyperlasia in the thyroid?

increased number of cells due to overstimulation of glands to produce thyroid hormones
thyrotoxicosis

what happens in graves disease?
how do the cells look?

autoimmune autoantibodies stimulate TSH receptors on follicular cells
cells appear columnar with little stored colloid
tumour like nodules

what is the main thyroid cancer?

adenocarcinoma of follicular cells

how many parathyroid glands are there, where are they normally located?

normally 4
posterior surface of thyroid glands
can be up to 8

embryology of parathyroid glands,
from which pharyngeal pouches do they develop?

3rd and 4th
migrate down

what do the parathyroid glands secrete?
what is this hormone involved in?

parathyroid hormone
involved in calcium homeostasis

what does PTH do, and how?

increases serum Ca2+
-osteoclast reabsorption of bone
-increased ca reabsorption in kidney
-increase ca uptake in gut

What is hyperparathyroidism?
-primary
-secondary

excessive secretion of PTH
-primary\= tumour
-secondary\= kidney failure

how does kidney failure cause hyperparathyrodism?

no reabsorption of ca
increases PTH secretion
more bone resorption

what care needs to be taken when removing parathyroid glands?

thyroid gland
recurrent laryngeal nerve

what is the structure of the parathyroid glands?

Clusters of glands surrounded by connective tissue capsule septa that infiltrate gland body and carry blood/lymph/nerves

what cells are present in parathyroid gland?

Main secretory cell is the pale chief cells (P).
Other darker-staining cells of unknown function are oxyphil cells (O).

what is the functional unit of the thyroid?
where are hormones made?

follicle
hormones made in follicle

what is colloid?

viscous, protein rich storage unit of hormones

what is the chemical structure of T3/4?

tyrosine amino acid
with iodines attaches

what is tyrosine?

chiral carbon
carboxyl
amine group
r chain
aromatic ring
oh on c4

how are thyroid hormones made from tyrosine?
1. what 2 points can iodine be attached, what does this make?
2. what iodotyrosines are coupled, to make what?

1. iodine attached at 3'
\=MIT
iodine attached at 3' and 5'
\=DIT

2.
DIT + DIT\= T4
MIT + DIT\= T3
DIT + MIT\= rT3

what is rT3?

inactive
antagonist at T3 receptor

what are most thyroid hormones present as?

T4

what 2 things are needed for thyroid hormone synthesis?

source of iodine
source of tyrosine residues

where does source of iodine come from?
how does it enter the body?
via what transporter?
and what is required?

comes from diet
active uptake of iodide across basal membrane into follicular cell
via sodium-iodide symporter,
requires ATP hydrolysis

steps of thyroid hormone synthesis

1. iodide in follicular cell transported across apical membrane via pendrin molecule
2. iodide oxidised via TPO
3. thyroid hormone synthesised on thyroglobulin
4. thyroglobulin transported into colloid by exocytosis
5. organification, tyrosine molecules are iodinated
6. MIT and DIT coupling\= T3/4
7. but still attached to thyroglobulin
8. iodinated Tg stored in colloid

what is TPO?
where is it located?
what does it do?

thyroid peroxidase
integral membrane protein
on apical membrane
iodide-\>iodine

what is thyroglobulin (Tg)?

large glycoprotein with many tyrosine residues
not all tyrosine is exposed

what are the major steps in thyroid hormone synthesis?
what are they catalysed by?
where does this occur?

oxidation of iodine
iodination of tyrosine molecules on thyroglobulin
coupling of iodotyrosines

thyroid peroxidase
apical membrane

how is thyroid hormone released?

thyroglobulin taken up by endocytosis
vesicles fuse with lysosomes
proteilysis
T3/4 release into plasma

release mechanism of T3/4?

unclear
lipophilic so readily pass
attached to TG\= cant be contained for exocytosis
once cleaved by proteases, they just diffuse out

regulation of thyroid hormone secretion

endocrine axis
T3/4 has negative impact on ant pit and hypothalamus
TRH and TSH stimulate thyroid gland

what does TSH do to thyroid gland?
what type of hormone is it?

regulates it, stimulates synthesis and release of T3/4
trophic hormone
maintains integrity of thyroid gland

what 5 steps does TSH increase?

Na+I- symporter
pedrin
endocytosis
lysosomes
release

what happens in TSH excess?

increase size and number of follicular cells

what other factors regulate thyroid hormone secrtion?

cold ^TRH
stress decreases TRH, ^somatostain, decreasing TRH

How are thyroid hormones transported in the blood?
and why?

bound to carrier proteins
because they are lipophilic
when bound they are biologically inert, free hormones bind to receptor

what carrier proteins do T3/4 bind to?
%

thyroxine binding globulin (TBG) -70%
transthyretin 10%
albumin 20%

what thyroid hormone is a better measure of thyroid function?

free T4 not total T4

What do deiodinase enzymes do?

gradually remove iodine molecules off tyrosine
T4 -\> T3
some T3 -\> rT3

what is the route of T4 dependent on?

isoform of deiodinase enzyme

T4 function as \___
T3 is the \___

T4 function as prohormone
T3 is the active hormone

how do thyroid hormones increase metabolism in the body?

increase metabolism of CHOs, proteins, fats
increase O2 consumption, heat prod
^BMR
^functional activity in almost all cells

what are thyroid hormones synergistic with?

SNS
catecholamines

what do thyroid hormones upregulate?
what does this do?

expression of B-adrenoceptors
mediate effects of adrenaline and NA

how do thyroid hormones act?
what happens once they bind to receptor?
what does it effect?

bind to intracellular receptors
promote genes
change in gene expression\= change in protein level and function
direct effect on mitochondria\= ^metabolic activity

what can affect peripheral conversion of thyroid hormones?
what will this affect?

altered deiodinase activity
kidney, liver disease, stress, drugs
alter T3 levels, lower metabolic rate

what is a goitre and what are the 2 types?

enlarged thyroid gland
diffuse
nodular

what causes a diffuse goitre?

overstimulation of thyroid gland by TSH or TSI
graves, thyroid stimulating immunoglobulins

what is a nodular goitre?

A discrete area that is clearly different from surrounding thyroid gland
thyroid tumour

what happens in hypothyroidism?

fall in T3/4

primary failure hypothyroidism
what happens?
what causes ?
what does it impact?
goitre?

something wrong with thyroid glands, not enough hormone prod
autoimmune
less T3/4, less activation of -ve feedback loops
^TSH but no stimulation because thyroid gland failed
diffuse goitre
^TSH, trophic effect

secondary hypothyroidism
goitre?
impact?

hypothalamic, ant pit failure
low TSH low T3/4
no goitre
low TSH could lead to atrophy

what happens to thyroid when there is lack of dietary iodine?
is there a goitre?

missing component for T3/4
less -ve feedback
^TSH
goitre

what are other causes of hypothyroidism?

drug induced
radioactive iodine therapy
thyroid hormone resistance

signs and symptoms of hypothyroidism

weight gain
dry skin
hoarse voice, slow speech
cold intolerance
constipation
low HR/BP
depression, confusion, poor memory

what are the effects of hypothyroidism?

reduction in BMR and overall metabolism
myxoedema\= puffy face, hands, feet
facial myxoedema\= thick dry skin
cretinism in neonates

what will a thyroid function test show in \___ hypothyroidism?
-primary
-secondary

-primary\= low T3/4, high TSH
-secondary\= low T3/4, low TSH

what tests should be done if hashimoto's is suspected?

test for thyroid antibodies
anti-microsomal TPO, anti-thyroglobulin antibodies
some may be -ve for antibodies

goal of thyroid treatment?

euthyroid state

treatment for hypothyroidism?
what is treatment of choice?

synthetic thyroid hormones
levo-thyroxine T4

levothyroxine T4
dosing?
caution?
monitoring?

drug of choice, orally active, once day
may worsen angina, then use B blocker
baseline ECG with dosing

liothyronine T3
max effect
rapid onset\=
used in

max effect 24ht
not really used
can induce heart failure
used in severe hypothyroidism

What is thyrotoxicosis?

hyperthyroidism
^T3/4

what disease is the abnormal levels of TSI?

graves
thyroid stimulating immunoglobulins

what happens in hyperthyroidism secondary to excessive TSH?
will there be a goitre?

hypothalamic/ant pit secretion
^TSH
^T3/4
goitre

what else can cause hyperthyroidism?

drug induced

signs and symptoms of hyperthyroidism?

weight loss
sweating
tremor
nervousness, anxiety
goitre
heat intolerance
palpitations
exopthalmous
restlessness
diarrhoeao

what increases due to the excessive thyroid action?

cellular and tissue metabolism
enhancement of B adrenoceptors

what will a thyroid function test show in \___ hyperthyroidism?
-primary
-secondary

-primary\= ^T3/4 low TSH
-secondary\= ^T3/4 high TSH

if suspected graves, what test should be done?

thyroid stimulating immunoglobulin

if thyroid tumour suspected, what test should be done?

iodine uptake test
123I

goal of hyperthyroid treatment

euthyroid state
symptomatic relief from increased sympathetic activity

3 treatments of hyperthyroidism

anti-thyroid drugs
radioiodine surgery
B blockers

what are 3 antithyroid drugs?

thionamides
carbimazole
propylthiouracil (TPU)

how do anti-thyroid drugs work?
reponse seen after \__ why?
course for how long?
drug of choice?
if not drug of choice then ?

decrease T3/4 prod by inhibiting TPO
block T4-\>3 iodination (TPU)
response seen after weeks due to colloid storess
12-18months
carbimazole
if not then PTU

complications of carbimazole

rashes, pruritus
neutropenia, agranulocytosis
bone marrow suppression

what are the 2 approaches for using anti thyroid drugs?
which has least side effects?

-dose titration (less side effects)
-block and replace

dose titration method for anti-thyroid drugs

only anti-thyroid drugs used
dose adjusted to achieve normalisation of thyroid hormone production

block and replace method for anti-thyroid drugs

given with thyroxine replacement

when might radioactive iodine be used?
-dose
-effect
-result

nodular goitres
hyperthyroidism
thyrotoxicosis after anti-thyroid therapy
-single dose
-max effect seen after 2-4months
-hypothyroidism may occur

when might thyroidectomy be done?
-results in

severe thyrotoxicosis
large goitre
tumour development risk
obstructive symptoms
may result in hypothyroidism

what is obesity, and what is it caused by?

too much body fat
caused by chronic positive energy balance

BMI
\>23
\>27.5 high risk
for asians
means what?

increased risk of of CVD

what does measuring skin folds do?

relationship between subcutaneous fat and %body fat
biceps and triceps are common area

what is a good measurement of intra-abdominal fat?

waist circumference
waist:hip ratio

what risk increases with an increased waist circumference?

high total cholesterol
low HDL cholesterol
high BP

what are the consequences of obesity?

CHD
high BP
plasma cholesterol
T2DM
resp problems
OA
stroke heart attack
cancers