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1hyro|d and Ant|hyro|d Drugs

O 1he Lhyrold secreLes Lhree maln hormones


LrllodoLhyronlne %1
3
) 1eLralodoLhyronlne %1
4
thyrox|ne) and CalclLonln
O 14 and 13 are lmporLanL for normal growLh and developmenL normal
body LemperaLure and normal energy levels
O 14 and 13 conLaln 39 and 63 (respecLlvely) of lodlne as an essenLlal
parL of Lhe molecule
& Synthes|s storage and secret|on of thyro|d hormone
O 1he funcLlonal unlL of Lhe Lhyrold ls Lhe folllcle or aclnus
O 1hyroglobulln ls a large glycoproLeln each molecule of whlch conLalns
abouL 113 Lyroslne resldues
O L ls synLheslzed glycosylaLed and Lhen secreLed lnLo Lhe lumen of Lhe
folllcle where lodlnaLlon of Lhe Lyroslne resldues occurs
O 1he ma|n steps |n the synthes|s storage and secret|on of thyro|d
hormone are as fo||ows
DpLake of plasma lodlde by Lhe folllcle cells
ldaLlon of lodlde and lodlnaLlon of Lyroslne resldues ln Lhe
Lhyroglobulln of collold
ecreLlon of Lhyrold hormone
& 1he uptake of p|asma |od|de by the fo|||c|e ce||s
s an energy dependenL LransporL process occurrlng agalnsL a gradlenL
whlch ls normally abouL 231

& 1he ox|dat|on of |od|de and |od|nat|on of tyros|ne res|dues
O 1hls ls broughL abouL by an enzyme (Lhyroperoldase)
O L ls very rapld and requlres P
2

2
as an oldlzlng agenL
O odlnaLlon (referred Lo as 'organlflcaLlon' of lodlne) occurs afLer Lhe
Lyroslne has been lncorporaLed lnLo Lhyroglobulln
O 1yroslne ls lodlnaLed flrsL aL poslLlon 3 on Lhe rlng and Lhen ln some
molecules on poslLlon 3 as well formlng monolodoLyroslne (M 1) ln
Lhe flrsL case and dllodoLyroslne (u 1) ln Lhe second
O 1wo of Lhese molecules are Lhen coupled elLher M 1 wlLh a u 1 Lo
form 13 or Lwo u 1 molecules Lo form 14
O 1he lodlnaLed Lhyroglobulln of Lhe Lhyrold forms a large sLore of Lhyrold
hormone and Lhere ls a relaLlvely slow Lurnover of hormone ln Lhe
Llssues
& Secret|on of thyro|d hormone
O 1he Lhyroglobulln molecule ls Laken up lnLo Lhe folllcle cell by
endocyLosls of some of Lhe collold ln Lhe lumen
O 1he endocyLoLlc veslcles Lhen fuse wlLh lysosomes proLeolyLlc enzymes
acL on Lhyroglabulln and 14 and 13 are released and secreLed lnLo Lhe
plasma
O 1he M 1 and u 1 whlch are released aL Lhe same Llme are normally
meLabollzed wlLhln Lhe cell Lhe lodlde belng removed enzymlcally and
re used
& kegu|at|on of thyro|d funct|on
O 1hyroLrophln releaslng hormone (18P) from Lhe hypoLhalamus
releases LhyroLrophln (Lhyrold sLlmulaLlng hormone 1P from Lhe
anLerlor plLulLary as does prot|re||n
O omaLosLaLln reduces basal LhyroLophln release
O 1he producLlon of 1hyroLrophln ls also lnfluenced by a negaLlve
feedback effecL of Lhyrold hormones 13 belng more acLlve Lhan 14
O 1he conLrol of Lhe secreLlon of LhyroLrophln depends on a balance
beLween Lhe acLlons of 14 and 18P and probably also somaLosLaLln
O 1hyroLrophln acLs on recepLors on Lhe membrane of Lhyrold folllcle cells
and lLs maln second messenger ls cAM
O 1he oLher maln facLor lnfluenclng Lhyrold funcLlon ls plasma lodlde
concenLraLlon A reduced lodlne lnLake wlLh reduced plasma lodlde
concenLraLlon wlll resulL ln a decrease of hormone producLlon and an
lncrease ln LhyroLrophln secreLlon
O An lncreased plasma lodlde has Lhe opposlLe effecL
O 1he slze and vascularlLy of Lhe Lhyrold are reduced by an lncrease ln
plasma lodlde
O A prolong decrease of lodlne ln Lhe dleL resulLs ln a conLlnuous ecesslve
secreLlon of LhyroLrophln and evenLually ln an lncrease ln vascularlLy
and hyperLrophy of Lhe gland
& Act|ons of the thyro|d hormones
1 Lffects on metabo||sm
O 1he hormones are regulaLors of meLabollsm ln mosL Llssue 13 belng
Lhree Lo flve Llmes more acLlve Lhan 14
O 1hey produce a general lncrease ln Lhe meLabollsm of carbohydraLe faLs
and proLelns
O 1here ls an lncrease ln
2
consumpLlon and heaL producLlon whlch ls
manlfesLed as an lncrease ln basal meLabollc raLe
O AdmlnlsLraLlon of Lhyrold hormone resulLs ln augmenLed cardlac raLe and
ouLpuL and lncreased Lendency Lo dysrhyLhmlas such as aLrlal flbrlllaLlon
Lffects on growth and deve|opment
O 1he Lhyrold hormones have a crlLlcal effecL on growLh
O 1he hormones are lmporLanL for a normal response Lo paraLhormone
and calclLonln and for skeleLal developmenL
O 1hey are parLlcularly necessary for normal growLh and maLuraLlon of Lhe Cn
& Mechan|sm of act|on
O AfLer Lhey enLer Lhe cell 14 ls converLed Lo 13 whlch blnds wlLh hlgh
afflnlLy Lo speclflc recepLors assoclaLed wlLh unA ln Lhe molecules
O Jhen 13 ls bound Lhe recepLors change conformaLlon and acLlvaLe
LranscrlpLlon resulLlng ln generaLlon of m8nA and proLeln synLhesls
& 1ransport and metabo||sm
O 1he plasma concenLraLlons of Lhe hormones can be measured by
radlolmmunoassay
O oLh hormones are bound malnly Lo Lhyroln blndlng globulln (1)
O 1he Lhyrold hormones are degraded (ln Lhe llver) by de lodlnaLlon
deamlnaLlon and con[ugaLlon wlLh glucuronlc and sulphurlc aclds
O 1he free and con[ugaLlon forms are ecreLed parLly ln Lhe blle and parLly
ln Lhe urlne
O 1he meLabollc clearance of 13 ls 20 Llmes fasLer Lhan LhaL of 14
O 1here ls a large pool of 14 ln Lhe body lL has a low Lurnover raLe and ls
found malnly ln Lhe clrculaLlon
O 1here ls small pool of 13 ln Lhe body lL has a fasL Lurnover raLe and ls
found malnly lnLracellularly
& Abnorma||t|es of thyro|d funct|on
1 nyperthyro|d|sm %thyrotox|cos|s)
O n LhyroLolcosls Lhere ls ecesslve acLlvlLy of Lhe Lhyrold hormones
resulLlng ln a hlgh meLabollc raLe an lncrease ln LemperaLure and
sweaLlng and a marked senslLlvlLy Lo heaL
O nervousness Lremor Lachycardla faLlguablllLy and lncreased appeLlLe
assoclaLed wlLh loss of welghL occur
O 1here are several Lypes of hyperLhyroldlsm buL Lhe mosL common are
1 D|ffuse tox|c go|ter (Also called raves' dlsease or eophLhalmlc
golLer)
O aLlenLs wlLh eophLhalmlc golLre have proLruslon of Lhe eyeballs
O 1here ls also lncreased senslLlvlLy Lo caLecholamlnes

1ox|c nodu|ar go|ter
O 1olc nodular golLre ls caused by a benlgn neoplasm or adenoma and
may develop ln paLlenLs wlLh longsLandlng slmple golLre 1hls condlLlon
does noL usually have concomlLanL eophLhalmos
nypothyro|d|sm
O A decrease acLlvlLy of Lhe Lhyrold resulLs ln hypoLhyroldlsm and ln
severe cases myoedema
O L ls lmmunologlcal ln orlgln and Lhe manlfesLaLlons are
Low meLabollc raLe slow speech deep hoarse volce leLhargy
bradycardla senslLlvlLy Lo cold and menLal lmpalrmenL
O aLlenLs also develop a characLerlsLlc Lhlckenlng of Lhe skln whlch glves
myoedema lLs name
O PashlmoLo's LhyroldlLls a chronlc auLolmmune dlsease ln whlch Lhere ls
an lmmune reacLlon agalnsL Lhyroglobulln or some oLher componenL of
Lhyrold Llssue can lead Lo hypoLhyroldlsm and myoedema
O 1herapy of Lhyrold Lumours wlLh rad|o|d|ne can cause hypoLhyroldlsm
O 1hyrold deflclency durlng developmenL causes cret|n|sm whlch ls
characLerlzed by gross reLardaLlon of growLh and menLal deflclency
3 S|mp|e non tox|c go|tre
O A dleLary deflclency of lodlne lf prolonged causes a rlse ln plasma
LhyroLrophlc hormone and evenLually an lncrease ln Lhe slze of Lhe gland
O AnoLher cause ls lngesLlon of golLrogens (eg from cassava rooL)