Feb2 M1,2-Thyroid Flashcards
structures near thyroid
parathyroid glands
recurrent laryngeal nerve
composition of thyroid on histology
follicles made of single layer of epith cells (follicular cells or thyrocytes)
content of follicle cavities
colloid. amorphous eosinophilic material
active vs inactive thyrocytes
active = tall and columnar inactive = flat and cuboidal
species that have thyroid gland
all vertebrates (poikilotherms = cold blooded and homeotherms = warm blooded)
thyroid gland role in cold blooded vs warm blooded vertebrates
cold blooded = growth and development only
warm blooded = growth and dev + thermogenesis and metabolic effects
congenital hypothyroidism: main reason to treat as quick as possible
avoid developmental problems
why thyroid hormone said to not work in isolation
works with growth axis and reproductive (gonad) axis
hypothyroidism effect on puberty
puberty and growth retarded by a couple years (hockey stick sign)
how thyroid hormone influences BMR in homeotherms vs poikilotherms and how can be measured
homeotherms: increased O2 consumption. higher BMR
poikilotherms: same O2 consumption as no TH.
thyroid hormone molecule backbone + name without the iodine atoms
two benzene rings with ether linkage between them: called thyronine when no iodine atoms
T4 vs T3 vs rT3
T4: I on 3’5’ (outer ring) and 3,5 (inner ring) = 3,5,3’,5’ tetraiodothyronine
T3: 3,5,3’ triiodothyronine (lack 5’ I in outer ring)
rT3: 3,3’,5’ triiodothyronine (lack 5 I in inner ring = bio inactive)
other name for T4 (when 4 iodines)
thyroxine
2 atoms important in thyroid hormone synthesis
iodine and selenium
3 pools of iodine in the body
- exchangeable (plasma inorganic I)
- Organic pool (I attached to T3 and T4 and to TGB: thyroglobulin)
- Stored in thyroid (most of iodine)
how to determine if someone is iodine deplete
urine iodine. if too low, means I deficient
iodine conc in thryoid vs plasma
200x more
transporter on basolateral surface of thyrocytes + fct
NIS (sodium-iodine cotransporter). Na+ and I-
what drives energy of NIS (Na I Symporter)
Na K ATPase
4 ions that can compete with iodine on NIS
perchlorate, pertechnetate, thiocyanate or fluoride
why iodine makes its way to apical surface of the thyrocytes
can’t remain in the cell. hallogens are very reactive and corrosive so need way to store it and not destroy the cell
What makes iodine exits thyrocytes on apical surface
pendrin: an iodine-chloride exchanger
inside what large protein is TH produced
thyroglobulin (TGB)
3 functions of TGB
- Storage
- template for TH synthesis
- autoregulates TH synthesis
TGB protein structure
dimers. 330 000 kDa
TGB produced where and stored where
prod in thyrocytes
stored in colloid of follicles
TGB: relative amount of tyrosine
not that much
TGB tyrosine residues where and name for that site
strategic sites (close to each other) so that enzymatic rxs are efficient: called hormogenic sites
hormogenic sites fct (sites where tyrosine residues strategically placed)
serve as template for TH synthesis
other name for hormogenic site of TGB with the tyrosine residues
tyrosyl residues
iodine vs iodide
iodine = I iodide = I- (think d = deficient = negative)
3 first steps of TH synthesis
- iodide conc into the cell (NIS)
- moves to apical surface (unknown mech)
- iodide conc in colloid (by pendrin)
tyrosyl vs tyrosine
tyrosyl is the radical, or a.a residues, of the a.a tyrosine
next step after iodine conc in colloid (2)
TPO (tyroperoxidase) does 2 things
- oxidize iodide to iodine
- attach iodine covalently to tyrosyl residues to make MIT (monoiodotyrosyl) or 2 iodines to make DIT
Importance of TPO step
is a rate limiting enzyme
What TPO does after it has created DIT and MIT
attaches them together
MIT + DIT = T3
DIT + DIT = T4
where is the TH formed from DIT and MIT and why
it is in TGB and is stored in TGB (all steps to its synthesis were done on TGB. TGB = template)
how much reserve ot thyroid
for 4-6 weeks
How T3 and T4 move from colloid to blood stream
thyrocytes endocytose pieces of colloid. phagosome fuses with lysosome to make phagolysosome. T3 and T4 then secreted in blood stream
how does body avoid losing iodine stores
MIT and DIT are not secreted (tyrosyl residues) but are recycled
T4 (thyroxyl) produced where
thyroid gland only
T3 produced where and how
30 ug daily
20% (6 ug in thyroid)
80% (24 ug in liver or kidney from conversion of T4 to T3)
what proteins convert T4 to T3 and give 2 of them
selenoproteins: deiodinase type 1 and type 2
deiodinase type 1 location
liver and kidney
deiodinase type 2 location
brain (hypothalamus included) and brown adipose tissue
which protein can deactivate T4 and is responsible for the load of rT3 in the blood + what it does
type 1 deiodinase (can both activate and deactivate T4 therefore: to T3 or rT3)
remove I on pos 5
metabolic pathway (of thyroid hormone desactivation or elimination) other than conversion to rT3 + when it happens
conjugation via enterohepatic pathway. (decrease amount of T3 T4 returning to circulation)
in hyperthyroidism for ex
T4 vs T3 + which is responsible for most of the activity of thyroid secretions
- T3 10x more affinity for nuclear R than T4
- T3 10x more potent than T4 (active = T3, prohormone = T4)
- T3 10x more abundant on nuclear R than T4
what stimulates thyroid to release its hormones
thyrotropes of anterior pit release TSH (or thyrotropin)
group of pituitary hormones that have similar structures and that TSH is included in
TSH, FSH, LH, CG
TSH, FSH, LH, CG: things in common
glycoproteins
alpha subunit in common
TSH, FSH, LH, CG: what makes them different
beta subunit specific to each: responsible for ligand-R interaction
TSH-R vs TH-R
TSH-R is on cell (thyrocyte) surface
TH-R is a nuclear R
what is really responsible for the activity of TSH + what makes it
its carbohydrate moiety group (CHO moiety). TRH of hypothalamus responsible for glycosylation of TSH
TSH amount if hypothalamus damaged
normal amount but is inactive (no TRH)
problem in immune assays detecting TSH
detect beta subunit but can’t detect degree of glycosylation (and therefore how much TSH is active)
what determines TSH’s half life
CHO moiety
what exactly produced TRH
paraventricular nuclei of the hypothalamus
can you have hypothyroidism if normal TSH levels?
yes, if hypothalamus is damaged, will detect normal TSH levels with immune assay but in fact TSH inactive bc no CHO moiety
how TSH transmits signal to thyrocytes for TH release
binds membrane R and activates 2 downstream GPCRs
earliest effect of TSH on thyroid gland
(release of preformed hormones)
- TGB endocytosis
- degradation and release of iodo a.a
- intrathyroidal deiodination of iodotyrosines
TSH effects on steps on TH synthesis (which stim and which are not)
increases NIS activity, iodide oxidation to iodine and organification, coupling of DITs and MITs,, TGB synthesis and procesing
DOESN’T increase pendrin activity (iodide-Cl exchanger)
what is believed to upregulate pendrin (even though real mech is unknown)
TGB (bc remember it has TH synthesis regulation fct so may act to upregulate pendrin on apical surface)
why moderate levels of hypothyroidism look normal
will see normal T3 in the blood bc high TSH from low TH stimulated thyrocytes to prod more TSH AND TO CONVERT T4 TO T3 IN THE THYROID
how TSH works to stimulate more conversion of T4 to T3 WITHIN the thyroid
upregulates (increases expression of deiodinase)
hypothalamus (paraventricular nuclei) 2 roles in HP-thyroid axis
- make TRH
- has deiodinase type 2 converting T4 to T3
feedback loops in TH and relative importance
T4 and T3 feedback on pit and hypot
hypoth feedback is even more important
why thyroid test complicated
other influences on HP-thyroid axis like neuropeptides, ntrs and hormones
external players doing positive regulation on HPT axis and where they act
cold, catecholamines (NE, E,..), CART, hormone leptin. act on hypothalamus
external players doing negative regulation on HPT axis and where they act
- cortisol and dopamine on hypothalamus
- somatostatin and dopamine on pituitary
sick euthyroid hormone syndrome def
abnormal thyroid fct test (TSH, T3, T4) but HPT axis seems to work normally bc of these external regulators
symptoms of hypothyroidism
sensitive to cold, slow mental process, low memory, weak slow heart, muscle weaknes, fatigue, constipation, thick and puffy skin, goiter sometimes*
possible complication of extreme case of hypothyroidism
pneumonia, can lead to myxedema coma
skin manifestation (important) in hypothyroidism
yellowish, thick, swollen, edematous (but not bc of fluid. it’s not edema)
all that bc deposition of mucopolysaccharides in dermis and subcutaneous tissue
hyperthyroidism symptoms
good appetite but weight loss, restless, anxious, hard to sleep, tremor, fast and strong heart, goitre
4 systems impacted by hypo or hyper T
- brown adipose tissue (thermogenesis)
- brain and cognition
- CVS
- Digestive system
thermometer area of the hypothalamus + how it controls temperature
preoptic area. has body projections to contorl tissues and organs responsible for heat prod and dissipation
normal response to cold
vasoconstriction, shivering
main mechanism of heat production and what controls it
brown adipose tissue (very active organ). thyroid controls it
main mechanisms of heat dissipation
perspiration, hyperventilation, vasodilation
2 components of BMR
- obligatory constant minimal energetic cost of living (breathing, heart beat, etc.)
- variable energy expenditure
thermoneutrality def
state where mechanisms of heat prod and heat dissipation are equal (is at 23 C)
temperature at which thermoneutrality is reached
23 c
name of mechanism that kicks in below temp of 23 to increase heat production
facultated or adaptive thermogenesis (includes shivering)
FT or AT (facultative or adaptive thermogenesis) is what % of BEE (basal energy expenditure)
0-15%
why body naturally produces heat
- lot of energy invested to make ATP lost as heat
- ATP conversion into work: heat loss there too
facultative (or adaptive) thermogenesis def
ability to render our thermodynamic system inefficient (lose more E to heat and less serves to make ATP)
how TH allows facultative (adaptive) thermogenesis in brown adipose tissue
- more ATP consumption and turnover
2. facultative thermogenesis (more E lost in heat)
when brown adipose tissue is metabolically upregulated
when need important heat production (like when in the cold) and not being an obese person
thyroid hormone exact mechanism of action on brown adipose tissue (and which TH)
T3 mostly (bc is the active hormone): upregulates uncoupling protein which goes in IMM and lets H+ flow down conc gradient passively
other term for hyperT
thyrotoxicosis
how minimal energy for living and BEE vary in hyper and hypoT compared to normal
same minimal E used for living
greater or lower BEE.
why hyperT complain of heat intolerance exam
are more comfortable at 18C because more of their E is lost to heat
why hypoT complain of feeling cold exam
generate less heat. more comfortable at 25C (use UCP less)
how brain affected by thyroid problems (in hypoT for ex)
memory problems, low ambition, depression. myxedema (or myxedema coma), accum of polysaccharides under the tongue so prob of speech
myxedema definition
synonym of hypoT that also includes the dermato features (of mucopolysacch deposition)
effects of hyperT on the brain young vs old adults
young: hyperactivity, insomnie, tremors
old: low appetite, weight loss, dyspnea
why old adults have apathy as consequence of hyperT and name for that
apathetic thyrotoxicosis. TH downregulates catech. (serotonin is one) in CNS
TH effect on CVS: heart itself
TH increases chronotropy and inotropy
TH effect on CVS: circulation
hyperT = vasodilation (get blood to brown adipose tissue) hypoT = vasoconstriction
hyperT vs hypoT effect on hemodynamics and CO
hyperT = less BP, less afterload. high CO hypoT = high BP, high afterload. low CO
hypoT important effect on vessels + consequence
ats bc of high BP, high serum cholesterol (but ats has no effect bc low O2 demand)
danger in treating hypoT too quickly
can precipitate MI
hypoT possible defect in the heart
pericardial effusion bc of leaky capillaries and vasodilation
hyperT effect on the heart
hyperdynamic. can get dyspnea from increased O2 demand
hyperT possible disease it can cause to heart and treatment
high output HF with pulm edema
give furosemide
hyperT effects on digestive system (2)
- diarrhea (frequent passage of stool)
- elevated liver enzymes
hypoT effects on digestive system (4)
- NAFLD (high cholesterol so try to pack it in liver)
- metab syndrome
- ascites (leaky capillaries)
- constipation
bowel complication of hypoT
Ogilvy syndrome. bowel distension bc of paralysis of intestinal wall (paralitic ileus)
test to dx thyroid function
TSH and T4 levels
high TSH low T4 shows what
primary hypoT (problem in thyroid)
low TSH high T4 shows what
primary hyperT (and suppresses hyp TRH and pit TSH)
high TSH high T4 shows what
secondary hyperT (pit adenoma producing unregulated TSH)
low TSH low T4
central hypoT (secondary if pit, tertiary if hypothalamus) hypoT (something injured pit or hypothalamus)
why TSH best test for thyroid function
very sensitive and responds a lot to TH levels. can have normal T4 and high TSH, showing pre hypoT
subclinical hypoT def vs overt hypoT
normal T4, high TSH.
overt hypoT is low T4 high TSH
treatment for overt hypoT
give levothyroxine (T4)
subclinical vs overt hyperT
subclinical: normal T4 low TSH
overt hyperT: high T4 low TSH
how quickly T4 and TSH normalize after treating hypoT or hyperT and how to follow up
T4 normal quickly. TSH 4-6 weeks.
Ask for side effects after 10 days.
wait 6 weeks to check if dosage correct
2 tests for hypoT other than lab
- ultrasound to check for lobulated bossylated enlarged thyroid
- serum TPO Abs to check if they have been released after an autoimmune (cellular, T cells) killing of thyrocytes
Grave’s vs Hashimoto thyroiditis
Grave's = specific disease where autoimmune agaisnt TSH-R makes gland hyperT Hashimoto = autoimmune killing of thyrocytes (give hypoT)
hyperT test
thyroid synthygraphy give iodide isotope to check where it is present and identify the overactive cells (it will enter through NIS)
diseases included in Grave’s disease (autoimmune hyperT)
- diffuse homogenous hyperactivity
- toxic adenoma (benign tumor producing TH independently)
- toxic multinodular Goiter
toxic adenoma of thyroid (hyperT) pathophgy
gain of fct mutation in TSH-R. benign tumor makes TH all the time
Grave’s disease pathophgy
Abs to TSH-R. (makes R think there’s TSH binding it). always producing TH
central hypoT usual cause and treatment
- cause: non functioning microadenoma (thyrotropes in pituitary destroyed)
- treat: TH for life
3 stages of thyroiditis
thyrotoxic (hyperT), hypoT, recovery
thyrotoxic stage of thyroiditis
initial destruction of thyroid allows release of large reserve of TH (hyperT for 6 weeks to 1 year max)
hypothyroid stage of thyroiditis
hypoT bc no more TH (destruction of thyrocytes) until recovery. can last a year
recovery stage of thyroiditis and what if it doesn’t happen
- may get recovery of thyroid and recovery of TH synthesis.
- if it doesn’t happen: years-lasting thyroiditis
