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Scenario:
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Puan Gopi, aged 40, prAsented fouryears ago w,ith a swelling in front of the nec[<which Brraduplly incrcased in size. She ngticed that she hidlost vi;Jjght despite a gooo appetite u,.la fuc.l! *o.ri"a and 'lecided to see her family doctor. on further cfuestioning, she addeclthat she irad palpitations, excessive sweating and trerror. The doctor prespribed some oral medication and after tating the :'
medication, her symptorns improved. She is still on the same medication but at a reduced dose.
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Learning objectives:
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E Embryology, gross anatolny and histological fgatures of thyroid gland. E Physiology of thyroid hormone secretion.
E Biosynthesis of
thyroid hc,rmones
:'
E Pathophysiology of hyperthyroidism.
E]
hyperthyroidism :
and radiological
El
- biochemical
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Gross Anaior'rr)' of
Tfhya"oii'rtr G{anc{
Locaticn:
.lla
In liont of larynx
ancl trachea.
rts: I-obes (right ancl 1eft) Apex: extenc'ls as far as the cbliclue line on lamina o1'thyroid cartilage Llase : iies at the level ol4tl' or 5tl'tracheal flng.
Isthrnus
Lies in
Relations (of lobes): Anterolatelaily (lronr deep to sr'rperficial): _ St"nloUlyroicl, Sterpohyoicl, Omohyoicl and SteLnocIe iclomastoid mu:cles'
Trachea EsoPha:gus
Comnton carotid
:Vagus nerve
Trar;ezius ntuscle
Posterolateral Iy:
Cryotid ,tr.ath (containing common ca1olid altel'y, intemal jugular vcin and vagus trerve)'
M:'diall,v
Lirlyrrx, llachea, plrarynx, esoplragLrs, cxtel.nal l'aryngeal nerve, Lecurrent laryngeal nerve (in the gloove betlveen trachea ancl esophagus), ,r
supEridr thyrojd
aGly
lob th)aold
brnchio.ephallc voin
Isthmus
rings.
.
Trachea
Thyrtoid
e'a'.
Trapezius muscle
i.
Superior thyroid arterY: a branch ofexternal carotid, descends to upper pole, the pretracheal external laiyngeal nerre is irnrnecli.ately behind the arteiy as it pierces gland' fascia and approaches the Llpper pole of thyroid irrjury to in thyroideciomy ligation of the'artery shoulcl be close to the pole to avoid
the nerve)
ii.
Inferior thyroid artery: - arises from thYrocervical trunk of subclavian, ascends l,ehind the gland to the levelthe of cricoids cartilage tlien turns nredially and clownwarcl to the posterior border of
iii.
giand. it divides outside the pretracheal fascia into branches rwhich pii--rce thc fascia ttetween
:
separately (recurrent laryngealnerye crosses either in fiont, behind or Dasses it tralches ,therefore ligation of the adery should be lvi:Il lateral to the glancl).
'Ihyroidea
-.
:-r
individuat;from-$rae+iioeephali+-+rude" ach-oJ-aorta -ol'r1gh! common carotid aitery and enters the lowerpart of isthmus'
ulo
ima:
of
5upE.i6f
'Fli
f:rteenrl
laryn3.crf ncrtu
thTr*d artcry
il_::i
Vrlit: ncr"c
Recu trenc
liyrrr d
3-frr'd
lrrTngral ncrvo
Iiierlor
rhyloid artery
lEch(:il_
i. ii. iii.
clrains into internal j Ltguiar vein. clrains into internal jugLLlar. clrains into lefl br:achiocephalic vein.
inltrior thyroid veins of the two sicies anastomose \.vitlt another in fi'ont of trachea).
lnf,
lh'/r*id
rt
I'lidLl le
lhyroid v
lubrlil'riofl
lnl. jugulor
In[, thtlr)1d
vv
$rochiorap|rlit tr,
i,
brorhiocupJnli< v
Lunpiiatic
cl r:ai n
E ts
age:
to paratraiheal nodes'
which is not ar,herent Thyroid gland is invested in a sheath d-erlved. from pretracheal {ascia except biween the isthmus ancl2"d, 3-'d& 4th' tracheal rings" the It is attached above to the hyoid bone and obli{ue line of the thyroid cartiiage and therei'cre thyroid gland followsthe movements of larynxiin srvallowing
ll,.
(IUL)
Origin: r -nd r;, o_ zrh n Thyroid gland is derived fro.m the Endoclermal thickening l,etween l".ancl 2"",'i" &' 4"' ol the ;ioor of pharyngeal arches (between Tuberculum impar anrl Copula) in the midline
. ' . E n F d
pharynx. iiito 1he unti":rlying Endociermal thickening becomes a cliverticuliim which grows inferiorly mesenchyme and forms the fhyroglossal duct. a The cluct elongates anci its djstal end irecomes bilobed and the proximai patl becrrmes solid cord. the The bilobed terminal srvellings expand as a result of epithe'tial proliferatic;n lo hrm thyroid gland.
-th }veeK /
Thyroicl giand reaches its finalposition, Solict corcL between tlie thyroid glancl and'the tongue disappe; rs,
-of
---
- ----r-_-+jte-of-origin-o+hyrogJossal-duct--orrthe dorsUn
'Foratnen Cecum'
p_iL
called
stage the thyroici gland consists of solid ma..,; ot- cells but later tl-:e mass brokens up into pt"t.s and eords by invading lhe vassular mc:.enchmaitissue Finally the plates and cords become srnall clusters of cells.
In the early
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u-:n!rnl!r
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riiaiu iir iiie terricr oiuleir ceii ciusier anci rirLrs foiiicles are formecl. PalalollicLrlar C cells (ivhich produce calcitonin) at'e derivecl lrom IJltirnobranchial body. Fibr'ous capSule ancl connective tissLre aie derivecl fi'orn thc sirrrounding rnesenchyme.
acai.iit-r
{'oliirici slfiits to
lilr{jlr.
lltrilrlr;ri,...
,tJlr:.i
F a E s * s
Tncomplete desccnt
At any point betr,veen the base of tongr-re aiicl trachea. Lingualthyroicl is most common among the incomplete desce,tt anomalies.
Ectopic th)lroi cl tissLre Occasionally found in the thorax in relation to trachea, bronchus or evell the esophagus.
Usually appears irr chitclhoocl or yotrng ndtrlts. Thyroglossal cyst - ' A?Vtii" remnant of thyroglossal clr-rct,that rnay lie at any lroint aloug the ttriglat'rrv pathr,r'ay of the thyroicl gland. - Always itt ot' near thc midlirrc of tlre neck. - 50% are close to or iust inf-erior to body o( hyoid bone.
ThyLogiossal
fls[ula
.;'
.
'ntl Erttirrcrine
Derivatives
Glantls
91,t" Ilassall
Pouches
1rt
2n,t
Derivat
Tubotympanic recess; Midd
Palatine tonsil
Auditoly rube
rrd
(+
Thymus;
Inf'e r:ior
parathyroi
Parafollicular (C) cell of th1 i'oid gland Ultimobranchial bocly tt Thyloid gla.nd is der:ived fi'om the Endodennal thickening between l an.-l pharyngeal arches (between TLrberculLim irnpar and Copula) in the midline
pharyn x.
8z
4'h
of
Figr:r'c 1. Note the line collagenous seltta (S) that arise flonr the fibro-elastic connective tissue c:ipsrrle oIthe tltyroicl gland extencling into the glar-rcl arrd also conveying blood vessels, lyrnph:ttics tr.rcl nerves.
Figuru, 2. Note the thyroicl lbllicles lined by follicLrlar cells which are simpie cuboidal cells.
9
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Thyroid l'ollicles are fillecl with a glycoprotein complex calletl thyroglobulit,, also ltnown
as colloicl, wl-rich stores the thyroid hoLmones (T3 and Ta).
witlr very litt,e amottltt of colloid or coltttnnar. Tlfgl$LlYpg-q'cells are the firlli cells are relalively tall
are ,small
ancl the
s
o o
When less active, the follicies aLe distendecl witli stored colloid and the lining ceils appear fl attened (tow cuboidal). The functional uirits of tlie thyroicl glancl are the tliyroid follicies, lined by a single l;ryer of (1't type of cells) cuboidal epithelial cells or follicular cells bounded b;'' a basement
membrane.
Figure
2nd
tvpe of cellq:
Parafoliicular cells or C -cells are founcl singly or in smal1 clumos in the interloilicular spaces, These cells are 2 to 3 times larger thari follicular cells" *ThEserells @secrsts calcJtqnb *vhiehlowers-the$lsed ealcium le:reL
Clinical correlation:
Iodine deficiency goiter. Cretinism in hypothyroid childLen. Hyperthyroidism is common in Graves? disease.
10
FKSVSKffiLffiGV
*ir$lyslology
{Dr"
Mah Kli}
(T3)
every tissue
T.l
T3
Ta
then becomes the biologically active horrrorre resporrsible for the majority of thyroid hormone elfects
of Tj
Ta ancl T3 is
Transthyretin (TTR), a'so callecl thyroxine-bihding prealbumin (TBPA), binds about I0%-1-S% Albunlin binds about
r'%
Thyroid-Stimulating Hormone
{TSH}
.
"
'i-;t-e--al
e;d
<otorie
sigrnals
.wF*4@>
S.i-inrul.cle
\ ," (
'*i Pil'uilcry
"e//@lnhibir
ru +u
-r.g'l{.-.dn>d<\q
,-t:
odinotiori
T"+.:--:**
i
rl
'-r3
Biosynthesis of
T+
and
T3
Deiodinose .<!*:*"+*
Bqsol membrsne
The process
includes
I
. " "
Dietary iodine (l) ingestion Active transport ancl uptake of iodide (l-i by thyroid
gland
I
Ta
ancl T3
Ta
and
T3
" '
lncrease mitochonclrial Size,Number and Key Enzymes lncrease Plasma inenrbrane Na-l( ATPase Activity Increase Futile Thern,ogettic Energy Cycles
Dccrease Superoxide Dintulase Activity
Untreated congenital hypolhyroidism or cltronic hypothyroidism during childhood can resuit in incornplete deveiopnlent and mental retardation
(CNS)
Thyro;ci hormones are essentialfor neui-al developrnent and rnatitration and function of the
CNS
"
"
' '
' "
,
lncrease tooth development and eruption lncrease growth and maturation of epidermis,hair foliicles and nails lncrease rate and force of skeletal muscle contraction tissue lnhibits synthesis and increases degradation of mucopolysaccharides in subcutaneor-is
Metabolic Effects of
T3
. '
LDL
from
plasma
'r
protein Generally stimulates all aspects of carbohydrate metabolism and the pathway for rl
degrad atio n
t',t'il '//
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_
Pa
Ta
"/' ,*\
Weight
Loss or Gain
Heat Intolerirnce
lncreasecl Sweating
Palms
,/
SLrdden Paralysis
f ir)L-Tri
or Diibetes
Graves Disease
" Autoirlntunedisorder
Production of TSH receptor autoantibodies Stimulate thyroid hormone overproduction
Charactei-ized by tire presence of B- and T-iymphocytes in thyroid tissue
TSH receptor activation
sodium/ioclide cotransporter
Auto a ntige
ns
(N
lS)
activity
l-lypothyro
Ca
iclisn-r
uses:
l*
ffigffiffFtrffiMg$T-ffiV
gliincl lrrocluces two principal horrrtorres --tltyroxiire (T.1) ancltriioclothyronine (T3), and also secrets calcitonin, a lrormone concernecl with calciunt ltorneostasis. l-: is about 4 times more active
T,,
than
ln lts biological functiols, and is l-0 tirnes more active in binding to the receptors. About B0%
ofTnis,ori,.rertedtoT3onenteringtoperipheraltissr"tes.Someamountof rT3withnegligible bioiogilal activity is also prodirced.l-3 &T4 require iodine for bioactivity, arrd are synthesized as part of a vei'v iar"ge molecule, ihyroglobLrlin which is stored in intracelluiar colloids. Thyroid hormones act by binC :rg to cvtosolic receptors very similar to steroid hormone receptors.
ln the einbryo, thyroicl horrnole is necessary for trermal clevelr:pment. l'"iypothyroidisrn in the
embryo is resporrsible for cretinism, which is characterized by rnultiple congenitaldefects and mental ietarciation.
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ii
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F.r /\i
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Frlir,ll
la
lt
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Iril,rrlollry: he[31
tE
ilU-1\ l
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!-r't.il
t
I1
V 7
Rwrnr
iiiilj
Ta
and
T1
cf thvroid hormones
wlTtsr r-_oL LorD
FOr-r_lc;LJl_af r sPAcE
@e
IflY.r.-QrQ qF=!
L,_
l'. t\I
/=-R\sc.o,'ddry rsu,FJ
'\\
--\
\\
'-:C'l
Dutotttnrttott^
,u."*"",*
L;lsqlll5l
NrT rI DrT
I u"o-tv','
I
Thyroglobulin {TCb) is an iodinated ciinteric glycosylatecl protein produ' cd by and used :ntirel"' within the thyroid gland, lt is the. llrccutsor of T3 .Q-14. CllO accounts fot B-10% and iodir le aboiit. 0.2 -IVoof its wcight. lt consisls ollboLtt 5000 aniir,'.1 lrticlr. with 11-5 tyro: 'ne residue, eacil of rruhich is a potential site of ioclination. About 70%of iodide exisis in MIT & DlT, r hile 30% is in T3 & 1'0. Il
sufficient iocline strllply,
Ta:-1,
ratio is 7:1-.
-f3
E Ta in Tgb is synthesized in the basal porti0n ol'cell ancl nroves to the lLtmen, cts as a storage irf the colloid. After stimulation by TSH, colloicls reeirlei'thc cell and phag, iysosome activiiY incrc rses. Acid proteases & peptidases hytlrolyze Tgb into amiiro .rcids inclucling 1 . & Ta, which arc therr
discharged.
a) b) c)
ej)
e)
Stimulate the mctabolic activities ancj increases Promote prote in synthesis like steroicl
O7 cofisLu-rl
hort.i'roners.
Promotes intestinal absorption of glucose, irrcreasc gluconeogene:,ts, and glycogerrrlysis. Stimulate lipid turnover & ul,ilization.
Regulate water and electrolyte metabolisnl
':t-
:nC!
Lre
Li
TSI-1
irr
the plasnra,
Thvroid functioq assessmn! Measuremenl of BMR reflects thyroid activity. The estinration of PBI is .mployed to ass :ss thy,oid function. The normal PBI concentration is 3-B prg/100 nrl. ln recentyears, the concentration of ffa, concentratio ns a re:
Free T3 Free T4
To
-:. 80.:220
nT/dl
: 0.8-2.a ng/dl
Total T4
TSH
: 5-12 pLg/cll
i
: <10 piU/dl
Radioactive iodine uptake ancl scanning of thyroid glarnd are also used iirr diagnosis.
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u,r
p h ys i cl I o
Deiinii.l,;n: ilyrterlhyroiclisnrisaclinical synclronreresuitirrgfromtheeffectonthetissueso{excessive : cirr.uleiting tlryroicl hormones: l'3 and 14 leadingto an increased metabolic rate. rr Normal leves oi tlryroid hormones irr adult br7 ELISA melhod are: o TSH=0.2-3-3.8 micro U/ml and
o
Ca
uses;
o , o -
Utilommon causes:
ovarii
giystern:c i:,:a-il:,.es of Thyrcrtoxj,osis. l'ite features il.i 'i ille se{:rl only in 6rave's disease.
r\nr:rly
.*--------"'-"*,--'
flei]hl lcri
LIenorrn.:ti,a
--
{t
l,(
t
OslaflDr)(c:'
i ----- - - Y-
tt
til
Prelrb'al
nlyxoedefiu '
. e
iss
)11
$"ffi!lUI;\TT NC
nvcr,
cliseas+)
l)ituit:rry glrncl
/ ji'cdb:rtt { c.rntr,:l /
|
I I
r'w
1 i
/
ao$
//1'5ll
-+*
Nesrtive
\ \
\ \
\ \
/ :'. i'
.1T:
l.l,
\\it \'----i
ary !*t
\Yntrlcej
\i
\.1
^
l^;
6A
6& o
3-s.lli
GRA\iES DISEASL,
&
ss
rsr.r$ * / \ d
+F+
\/ I \-
ll'icFl'A:i E rl
a-jr Ll
(.1 . lT)
Anlf,)odies slknulale
TSH. rrc*'tors
Suppress,: j TSH
High Te1..
Ererhlii|
irunui sd in,1
;r'lttt
Fing Jtemnl
E;{:U:Sf T"/.Tj
sciFFrassg;rriH
Fig"2-3
:l
i,
ross:
, ' u
Dif lusely
Cut surface: firm ancl rneaty in appearance, vascular, sntooth, soft, capsule intact'
Craves'disqase is a common cause of
tityro|i horntonc.
wlrlt,lt cituse5 cnlargenrent r:f the ll rytoicl ;trlrl ot.liet
5yr r I lrtol t'ls 5l.lcll as e.xotrrlttlialrnos, Ite-aL itito[e:t atlce arirJ ;rnr.ietY
fli:r'r
rt;ll
tl tyroicl
Irrlarrlecl tliyroid
iinl)\,r\1.
Microscr.rpic findings
ts -l
too many tall colLlmnar cells, crowded, lryperplasia, papillae encroach on colloid, colloid
and scallopecl, stronral llrrnphocytes and lymplroid follicies seen
Key
is thin
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':
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.
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:l-tl';:...i;:
l.ti
.
Fhalrnnae ole
gy of thyroiel disorclers
A. Hyg,o'il-ryruidisi
ln general, the goal of thyroid replacement therapy is to replace endogenous thyroicl ltormone productioi"r, avoid iatrogenic thyrotoxicosis, and treat systemic complicationr; of severe hyoothyroidism.
Levoitryroxirie
l-evothvroxine is the treatr-nent of choice because it is well e"ibsorbed and has a half-lifr: cf 7 Cays which allows claily dosing and steady levels of T3 and T4 being reachecJ irr approximately fl weeks.ra The starting dose shoLrld take into consideration factors such as age, preexisiing coronary artery disease, and cardiac arrhythmias. A starting dose of 1.6 pg/kg/dey in healthy patients is recomirerrdecJ, birt in elder !y patients or those with r;rr cliac clisease, it would be pruclen:. io st;,rt at a dose oi 25 pg to 50pg once daii;r'.
Liothy rc irinc. Liothyrirrrirre il--triiodothryronine) is rarely used alone as thyroid hornrone repia*,nrent oecause it car, cause rapid increases in its concentration, which cot-rld be cietii,lental in eldi.-rly patients and ihose witlt cardiac disease, lt can be used ai:ng with levothyroxine when levothyroxine alone does not provide relief of symptcms.
Thyroiri extri:ct
Thyroici extract or rratural trryroicl hormone is pig thyroid glancl that has been driecl and crutshecl in porrrrder form. This is not a recommended thyroid hormone replacenrent becaLrse the amount of T4 and T3 can be variable and there can be an excess T3 in this preparation.
B. Flypr:rilryroid isrn Propylthio u i'acil Antithyroid medications sLrch as propylthioiiracil and methimazole act predonrinanllv b! interferinq with the organification of iodine, hence suppressing thyroid hormone levels. Because these agents block only the synthesis of nevrr thyroid horrnones, the siores of preexisting thyroid hormone within the thyroid glancl rnust be exhaListed filst before they cein be fully effective, which may take 3 to B weeks in patients with Gtaves' disease or toxic nodular goiter. Propyltlriouracil (pTU) is a ,-lerivative ol thiourea that inhibits extrathyroidal -l coirversir:ri of 'T'zl to 3 and is preferred for pregnant wornen wiih hyperthyroidism becausc it do,:s not cross tire placental barrier as readily as rnethimazole. lt is readily absorbed, r,ryith a serum half-life of I to 2 hours. lts duration of action is longer riran tl-ie half-life and shoLtld be dosed every 6 to eight hours. lts starting dosage is 10C nrg three tini':s daily, with a maintaining dose of 100 to 200 mg a
day.
Patients undergoing treatment with antitlryroid drugs should hi;ve their thyroid hormone ievels reassessed every 3 to 12 vrT6gks cluring dose iitr:rtioit to rnottitor for iatrogenic hypothyioiclisnr. Comrnon sii.lo cficcts iirclutcle ra.;hes, llrtti-ttLts, joint pains, ancl fever. Tl'rese can be treatecl sylllptomatically wtthottt discontinuing the rledicatiorr, but if :rrthralilia occul"s, it shoulcl ire discotttinttilcl because it can be a precLrrsor of a iltorr: :;lt'ir:tt:; polyarihriiis s"ndrot"l.lc. Agranulocytosis is the trost setious coirtplicatiorr arrd ffia! octrtr in ti 1 trl 0 " percent of patients being p;iverr anlith,vrolcl mcrlic;rticns.r0The rlsk is highr,:i i those taking propylthiouracil wiihin the firsi fcr,,i nonths of ther; rpy.
r
IV'lethimazole Meth!nrazole blocks the oxiclation of iocline in the thlrroid glanc ' lt is the cliurS' of choice in nonpregnant patie nts because oi'its etiiordable cost, iongei italf-lift , and lower risk of hematologic aclverse effects, it can h,e taken as a single claily dcse, improving patients'compliance to the meclicalion. The stariing dose is 15 io.30 mg daily, which can be given along with a bpta blocl<er. If the i atient beconits clinically ancl biochemically euthyroicl after one izear of merjicailiorr methimazole can be cliscontinr:ercl. ir,ol:rpse ntLry occLtr, ancl is ,1enerally seen within a yeat of discontinr-ting the medicatiorr. lf iltere is re l;tps,,',, antithyrcid iherapy carr be restarted ancj other options sirch as raciioactivi: iocJitre or sul:,,eily is
iiltal<e,
considerecl.
lodide
loclides biock the extrathyroidal corrversion ol T4 to T3 and inhibit rerlease cri thyroid lrormone. lt is prirrcipally Lrsed as acljLrncl.ive therapy br:lore emergei cy thyroicl sLlrgery, to recluce vascularity of the thyroid glanci !:efo'e si.irgery, atr,-l in failed therapy rrvith beta blockers.zr These are-. not used in the routine tt'eatilt:tr't of hyperlhyroidism because it tends to paracioxically incicase ;iotntone teie.tsc with clironic use.. Organrc iodicle radiographic contrast agents ruch as iopan ric acid or ipodate sodiunr ate rnore corrmr:nly uscrl than iirorgat:ic iodicies (eg. potassium iodide). lopanoic acicl causes rapicl and signilicant irihibition ol' peripheral conversion olTzl to T?r arrd qr;ickly ier-luces T3 levels. Potassium iodide (l-r-rgol solution) contaiirs 8 rng of iodicle perdrop, arnd i:, usecl ftlr the treatment of thyroid storm for 10 to 1zl clays ittiorto thyroiclectr,rtny. Beta=adrenerg ic recepto r bl cickei"s ol Beta blockers help to promptly alleviate lhe sympathomimetic ''nanifestalioir:: hyperlhyroidism (eg, palpilaiioirs, anxiety, lrenrors, and hcat i;,tolerance) regardless of its Lrnderlying caLrse. lrr paticnts with carciiac arrirythmras like:,int-is lachyeardia or atrial{ibi.iliation r,vit}r a rapid voiilrieular rcsponll) raic, beta blockers can fLlnction to conirol thc heart ratc. Propanolol, a nonselective bota blocl<er, is prnferred becilr.r:se nf its elirect ciferl on hyperirieta',olisttt and is inost comrnonly used, altiroirgh other beta blockeis can !re given.z: l)ropanolo; slr,o partially inhibits conversion of -f4 to T3 in the peripheral tissues.q Beta blockers may be the only treatmeirt requir--d in paiieirt:; rryith transient ii,rms of hyperthyrcidism, howerver, in patients witlr more sustained fclrr,rs of
hyper"thyrojclism (ie, Graves' clisease, toxic noduiar goiter), clefinitive treatment is necessa ry. Proparrolol close can start at 2O to 40 mg every B hours at-rci be increased progri.:ssively up to a lna.:liilutri darly close ol240 rng Lrntil sytlptonrs are conirollecl. Lbnger-acting beta blockers such as metoprolol and atenolol can also be used. ln caseswhere a short-acting parenteral agent ls needed, Esmolol can be aclninist..ted. Beta blcrcl<ers shoLrlcJ be Lrsed wrth caLrtion in patients with a histori.r of heart disease, cbstructive pulmonary disease, asthma, or Raynaud's phenomenotr.
5. Ranionctive iocCine theraPY Racjica,l6tive iodine caLlse: selective uptal<e ancl concetrtratiott in thyrocytes. Follorruirrg oral administration, it clestroys thyroid tisslte, thereby controiling -fhis is the treatnrent of choice for the rnajority of hypeilhyroiclism effeciiveiy. patie;is v,yitli Graves' clisease ancl toxic nodular goiier. Higlr dose radioactive ioclin*, theraly is recoirmenclecl irr elclerly patients, those with p,reexisting cardiac clisease, anr,l patients with toxic noclular golter or toxic adenomas. Its marin acir.erse effect is the clevelopmerrt of postablative hypothyroidism, which is nroi'e con-rrnonly seep irr patierrts with Graves' cii$ease. Lifelong monitoring of thyroici irorrrrone levels is irecessary because patienis develop tlris complication at a r.tte of lt% anpLrally. /irrotlrer side effeci is ihe transientworsening of hy'erthyroiciisnr during the first montlr of treatment due to radiation thyroiditis. Opthalmopaihy nray cleveiop or exacerbate in 15 percent r:f patients with Graves' in those who smol<e cigarettes. Lower dose radioactive clisease, "rp"iinlly can be used in those patierrts to redLtce the risk of iodine,: or preclnisone ophthalmopathy. Radioaciive iocline is contraindicated in pregnant or lactating women because it can readily cross tlre placenta barrrer and can be excreted into mill<. This can lead to an ablative effect to the infant's thyroici gland resuliing in hypothyroidism.
Tutorial Guide for Thyrotoxiccsis Syrnptcrns: Loss of weight wiiir good appetite
H..-.at
intolerance
Faisily
Pa!pitations
ii'
increased catecholamine sensitivity Decreased cardiac a-adrenergic receptors lncreased numbers of $- adrenergic receptors in the heart.
Tremors
l-eiior rp u I cr LrE,uL
"nd WeaktreSS
Passing loose
stools
Difficulty ln gettinSi up from the toiiet seat after going to the toilet because of weakness of muscles - Proximal mYoPathY
Eye
Fine tremor
\,,ri
'
ia
A.rialfib'illatiott
,l
Tiiyrotoxic
ca
rcliomyopaihy-Congestive
ca
rdiac faiIure
Gravds disease
increased vascularity of
tibial myxoedema - thickening of skin ove r llre tibia without pitting -Grave-s
cliseasL
Causes of thyrotoxicosis derlyi n g aeti ology Dia g i-r ostic fea"ilr: r*s Conrrnon causes Graves' disease Thyroid siimulatirtg iirntunoglobulin (TSl) binds to and stiirulates the thyroid lncreased llryroid raclioactive iocJine uptal(e lvitir difluso Lii)t.r;(e or] scail, pr,lsiiir,rt: thyrope roxirlase antiboclies; raiserl seruin tliy1,3i6 stirirulatiirl, iittmtlnoglslriliir, dif"fuse goiire; oph'thalnropatlry ntay []o prt?$efi1.
Un
Toxic acl en oma Motroclot ta I a it to i ton tou :-,ly :;'.'cietin g be n ig n thyroid tumour Normal to iltcreased thyroicl ri,rdioarctive iocline LrlJtake wjtl'r ari I,rpta}<e irr th,.r nodule on scan; thyroperoxidase ai-rtibodies abse nt Toxic multirrodular goitre [4Lrltiple ironoclc',rral arrtonomor-tsly secretincJ benign thyroid tumours Normal to increasecl thyi'oid raclioactiire iocljrie r-tptal<e with ft cal areas of ircrear':ci and reduced uptake on scttrt, 1.l-iyrope roxiclaso antibodies a1",,;ent
Exogenor,rs thyroid hormone (thyrotoxicos is factitia) Excess exogenous thyroid hormorre L-ovr; to undeiectable thi.roid raciioacti,'e iod'ile uptake, iow serum thyropei"oxidase values.
Painless postpartum
Autoimmune lymphocytic infiiiration of tliyrc;cl urith release () stored thyro;d hormone Low to uncietectable thyroid radioactive iodine uptake; thyrc,reroxidase atriilrotji*,s present; occurs within six montlrs after preqnancy.
Less cofmr"nen cau$e6 Painless sporadic thyroiclitis Arltoinrmune lyrlphocytic infiltri lioir of ihyroicl with release of stored thyroidhormone Low to undetectable thyroicl radioaclive iociirrc r-rptake;
preserrt -thyroper:oxicl ase antibocl ies
Subacute thyroiditis Thyroicl inflamrlation',,irilir release ol stc'red thyroid hr-'rmonr:; possibly viral Low to undetectable thyroid radioactive iodine uptal<e; low titre or absent thyroperoxiclase airtibociies. lodine induced hyperthyroidisrn Excess iodine l*ow to undetlctable thyroici radioactive iodine uplal(e.
lndur f ion oi thyroid autoirrmurrity (Gra',,es'disease) or inflarntnaiory thyroiditis lhyroid radioactive iodine r,iptal<e eleva'red in Graves' ciisease or low to undetectable in thyroiditis
Am iocl aro ne ind u cedthyrctoxicosis iodine inclr-rced hyperlhyroidisrn (type l) or
inflan'rnaiory thyroidiiis (type I l) Low to undetectable thyrcid radioactive.iodine uptake Rare ;)aLrss Thyroid stimulating hormrine(TSH) secreting pltuitary adenr rna PitLritrry aclcnoma llaised serum thyroid stimulating hormone and _-st-rbriirit willr raised peripheral serum thyroid hormones Gestational thyrotoxicosis Stimulation of thyroicl gland thyroid stimulaiing hormone receptors by hun-ran chorionic gonadotrophin Thyroici radioactive iodine uptake contraindicated in pregnancy. First tiir-ne ster,often in seiring of hyperemesis or miiltiple gestation. Molar pregnancy Stirntilat:on of thyroid gland thyroid stim r-r iating; h'rrmr:ne receptors by h uman chorion ic gonadotroph in Molar precjnancy
i
Strunra ovarii Cvariarr teratoma witlr dilferentiatiorr primarily into thyroid cells Low tc' undetectable thyrc,id radioactive iodine uptake (raised uptake of radioactive iodine irr pelvis)
Widelv rneiastatic furrctior,al follicular thyroid carcinoma Thyroic{ lrorn-rone productlort by iarge tumour masses"
Diflere,rtiated thyroid carc;noma witlt bt-ilky metastases; tLrrnour rac{ioactive iodinei,ptake visible on vrrhole-body scan
lnvesti.gations Eler.ratecl free Ta and /or T: and a suppressed TSFI confirnr the clinical diagnosis of thyrotoxicosis. Thyroicl stirnulating antiborly (TSH-i-eceptor antibody)is usually elevated in Graves disease.
Treatment moclalities
Medical
Su rge
ry
Radioaci;ve iodine
Medical : Antith'rroicl
rugs
Ptrease
inhib ts periirheral Block thyroid hormone synthesis by inhibiting tlryroicl peroxidise. Propyii.hisLrracil
conversion
of T, toT3.
( ;-2 years) Medical therapy must be administerecJ for a prolongt:d i;criod of time
severe agrarrul tcytosi'; Side effects: minor- rash, pruritus, arthralgiil, choestatic jaundice, more
(o.s%)
patients must be instructecl to ciiscontinue the i"nedir:ation and consult tlre physician if they cleve lop fever or sore lhroat because these symptoms m.rr7 irrdicarte agranulocytr:sis"
of B Patients are given B blockers usually propanolol unless tltere are contriindications to u:;e alion block,ers, during the acute phase of treatment tc ;rlie r,'i.rL,: symptorns dtt : to syrnpathetir'siinlu
like tachycardia, sweating etc. As the thyroid hormr.rttc lt'vels return
ta pe red
.
to iicrmal, the
B blocker is
Surgery g'ands artd Subtotal or total thyroidectomy is the treatment ol'choice for patients vvith very large obstructive symptoms, or nt ultinod ula r gla ncls.
preoperatively, patient receives 6 weel<s of treatrtreni: with antithyroicl '-irugs to ensure ihat th''-y are
"'lodine
is the
patients with severe thyrotoxicosis, very large glancis, or underlying he, rt disease shoulrJ be rendered euthyroid with antithyroid meclication before receiving radio;rctive iodine ber:ause t"lodine treatment can cause a release of preformed thyroid hormone nto the circulat;on urhich can precipitate carcliac arrhythmias ancl exacerbate symptoins of thyrr:toxlcosis ithrTroid crises)"
a period of 6 weeks ancl 2 months. Between IO%-?O% become hypothyioid within the fjrst yeai" of treatrnent, and thereatter hypothyroiclisrn occlr's ilt a rate of 3% to 5% per year. tJltime'ielv SC'.t/o to 80%
Serum free Ta and TSH levels should be monitoi'e d and rcpiacementwiltr levothyroxine
insiituieclif
hypothyroidism occurs
ffiAffiHffiLffiGV
R.rcliological lnvestigations of
the
-{"hyroid
Gland
The lhi,roir-J {,1;inrj is a hc.rrntort,: prodLrcing irutterfly-slrapecl glarrd locatecj at the base of the neck. It lies autcliul io the thyloicl iincl cricoicl callillgcs u1'the llrlynx ancl the 1'irstthree tracheal ring^s.-ti,e 1-h'7rc;icl Glancl, which is composed of a riglrt lobe and a left lobe, produces and secretes thyroicl horrnolres into the blooilstreanr. Tlrese horrnones regulate body ternperature, heart rate, blood
pressLrre, energy level, growth r,ate and weigltt.
Plain xlays of rhe necl< are nrit perl'onnecl lor diagnosing Thyroid abnormalities
Sornetinres a rttrost'ernal goiler can
,;
be
srrspcctecl on plain
{-ater:ii
of flie
neci<"
!.!1ir:t,
rl.r::
i..
iii;r,,.r'.',.,
ir-1:.:):,
i:':
'
i,
l
i.
::
':
,.,, i t. .,
, lr.'
!,
t, _ i::r:
t.':
i,.
,'- ] .1.11
i,.,
rt
i.'
i
The xray:; sholv a large softtissLre density situated anteriorto the trachea. The traclrea is cl,:viated lo tlre rilrlrt.
ULTRASOUND is the most corninon imaging moclality used to diagnose Thyroid diseases . Ultrasound uses sorrnd of very high frequeniiy to image organs .
hr
*n,.,;!;;jlrjiihlii4:
ae.'
tlrrJ
reflecte,:i bacl<
tultrasour-rci wave.s penetrate bocly tissues ,some signals are .'fi'rese signals are processecl ancl cornbined to generate an
irnage.
,";.
__
- -:: liirai!.
,l '.rr::'},:'r'::1,:,
',.1
Rt lobe of Thyroid
Left lobe
lf
i-lrr7r,'id
j.
,,,.,
i.
i;
Ultrasound images are described as :Hypoechoic - lesion appears black Hyperechoic - lesion appears white lsoecl'roic - iesion is same eclrogenicity as the thyroicl parenchyma.
U/S can differentiate betweerr solicl aird cystic lesions.
Benign lesions have well defined margins ancl unifornr echo texture
Solid lesion
Cysti
IF!{-+-.- :l'.rFTll=
::t;j]
.:,fi,f-J
,;]
r:ll
:1.,'1;"i.
].1
,.1
A numberof ultrasound features suggest an increased likelihood that a gir'en thyroid nodule malignant and they include:
is
microcalcification imacrocalcifications, by contrasl, are common in benign nodules); irregular margins; "tallerthan wicle" morphology (inciicative of solid rathri than fliricl natLle nodule); internal vascularity; enlarged cervical ll,rnpir nocles on the same:;ide of the neck The mOre Of theSe {oer,rres f h:r coon rho nrnrg lii<ely it iS i.O hre nralignant
olt he
lrreguiar rnargin
.
[1-] a hot noclule
area of no uPtake.
at,td
F----tilIiH
-1', , ,;
.:i'...;^
i-I'ii*,r;":,
t.,
-
,,,,
.i.1
.l . .-t
'
'
:ra,1
,' : , , i+,r'ii;+jr",-,,. -.i;'or1 ,,' ,.,:...t,j : ;4.;11; .,,,;1 .,:,.-]t,r-i' 'tl : i:,:tt':r' ;iil';';i::; . t',,,t.'' '''. i' 'i t'1"'.-,"...1 ;" ' .,1 -..',,.i, ['-rr,,o'.. ,l '' '.t,_i ., ,, .,, ,I :ul f1;''1 ",''.,.'1,!.=-., 'i'i-' i.
.
f;i;--t, iLi':-r..-,
,"., .
.
-a
I
'l'
;y -," i'
..
.;.
;.,. ;-v.'
,:'
'ij:.
r'
i1':
"t.l:r:.:r;,
,:
;
,,#1,-:j
:EJ
l
'l 'il'r:
.rLi
1
1l ''1j ', .:
,rl.,trrilJi:l:ia;
dense mass
as
Hypodense - darker I blacker than nornral Thyroid parenchyma Hyperdense * brighter than normalThyroid parenchynra lsodense - same dense as norrnai Thyroid pai'enchyma.
Atthe pl'esent time, magneti: resonance imaging (Mnl) has a limited role in characterizing of cervical lymph node thyroi0 nociules, although it appears to be effective itr the diagnosis
m
elastl
rs.
Axial section
of
ThYroid
as
-Bright
lesion
.
Black lesion
ffPL.THB lL.T
(e
.ff
il ffi A f; -,',i,|;t,{
J*
S fl
j1'r
ll{-,[
Il_
PL]I3I,{'C
Epitlenriology':
Clof ra! ()r'cr'', !clv:
Tlre 11,)st cortrnrorr thyloici rliselse which is o1'lrprtrusl iittpolt:rrrcc irr pLtblic lrealtlr is
hypothy,,roidism. It is because oi the ease in screening ancl treating them.Iodine Deficiency
I)isoldels (lDD) have ntultiirle ancl seriouts aclverse efl-ects inclr,rding cretinism, goitre,
irnpairc<-l cognitive fimctior-r. inrpailecl grolvtlt, jnJant Inortality,
I-ow Birth
'Weight,
and
stillbirths in a large ploportion of the r,vorlcl's population. The dcglec of impairment in iirnclion is relatecl to the sevelity of iodine deficiency. Even nrarginal degrees of iodine
cleficiency hiLve a r-neasurable impact on hutnan clevelopntent. fhere has been great progress
as
Iiealtlr Crganization showecl that the Global T'otal Goiter Prevalence (GTP)
at 15.8%.
Thyroici Diseases in Ivialaysia: Newborn screening began as t-ar back in 11991 as a congenital hypothyroicl screening
201 0).
199
From 2)01-2009, 576 neonales r,r,ere confirned to have congenital hypothyloiclism. As hypothi'roiclism is easily trea,ied tluough sci'eenings, it has become the rnain concem jn
lvlalaysia.
Seiami, {i et al (2010)
iuuong chilcile 'r aged 8-10 ycar,s old to cleterrnine tlte 'current iodine cleficiency stzrlus jn thecountry. IJcter';nination of tu"inaly iocline (UI) ancl palpation of the thyroid glancl were carried ont among 18,A72 ancl 18,073 childlen respectively wliile iocljne test of the salt samples was
rlone using Ii-apicl Test Kits ancl tire ioclornetric methocl. The resLrlts sliowecl tliat based on \,\,/HO/ i/. e l!-)l)lllltllClrjr ciirii'ia, thc
125riL,
T5iirpcrceniiic
of iocline cleficiency
disorclers
(IDD) with U1<l00 pg/L was 48.2')/oioSZ. Ci: 46'0, 50' l), higher among chiltlt'en
rioted residing in i'r-tral arcas thair in urbzrn areas. The highcst prevalence .rf UI<100 Prg/i- r'va-s among the aborigines
Hg. l, Degreo
l'. ,
\)"
,)u;/s
'i,
:.
ij^6
i) \
(t
M \P$,P
lodinP d.'lr jf nry
(< l0
l(i,)
p4/lj
i2k9
fl
El
irrllnil
fihk
loLLl9',i
Fti)
1,1/l)
RFI ol
rnns.q.rpd
Fs
(>lcl] fq,l)
\o drn
According to the above map, Malaysia is in the mild iodine deficiency range i'e. 50-99 microgram per litre as assessed tluough urinziry iodine
levels.
,i
A study
done by
sriU.leilts
endemic goitre was highest in the inlancl areas and the coast (44.9'l ,) foiloi.vcd
bf
inlancl area
inchide low iocline contentof soil and \,vater, inadecluate iodine conient in iocal fo,rds arrci low consumption ofmarine seafoocl. Stuclies reportecl in WHC br-rlletin showed iodine i, ilSl,'ffY lotv in hilly aieaS asin the I'Iimalzryas, the Alps iu Europe-ancl flre Andes of Soutt America' it
may cause the cijct to be cicficicnt in ioclinc and causing cnclcntic 8,ritre.
In
12,0O0 school children agecl 8-10 year-s. Based on the WFIO/ICC,IDD rcferertce,the stlri/ey
O.7o/o
statr-rs
in Salawak could
irti. ii,,r'.:ci
su:pl'. .risch'rols and longhouses in lDD enclernicaleas a lew yeals priot'to the sr,rrvey (Foo
a state-levcl prograrnme
tbr salt
iodization i,vas iaunchecl ancl fully implementeclby June 2000. fhe situation in Sabah has
zLs
rnonitoring of school chilclrenagecl 8-10 years in2002 fbunci the meclian urinary
ptgll
The slLrclies supportecl the hvpothesis that endemic goitre is also cleficient in the interior of the
countwesirecially in Kelantan, Sat'awak and Keclah. In the i,ear 2(){)[), the Malaysian Enclocrine
gr-riclelirie
zrnd
lor thyroicl
Refbrerice:
1. 2. 3. 4.
5. 6.
h)'pothyroidism sqreening
I{ypothyroidisrn
r,vho are previously undiagnosecl cases oi'tliyroicl illness present u.ith depression and/or cognitive cleficits, especially memory clisturban;e. They tend 1,-r be hLavv sei. often with gray hair, can be in their forties or older. The lethargy, iatigue ancl slo-,.ing oi ihought processes can be rnistaken for a depressive disorder.
Hyperthyro id isnr The patients can present with anxiety, sweating, trenror, racing thorrghtS, and hypr ractiviry. patients also present witli paranoid, manic or psychotic manifestati, rns.
511"1-t
Most
of the patients
'
Thyroicl cancer ightening and may have ps-,chological corSOQLrerlr.es that persist even once the cancer has been successfLrlly treated. once rreviously healthy inclividrrals are told tl-rat they have thyroicl cancer, it is qLrite conlllon to experir nce solre clegrce of parric and becotne fi'iglitened. J'his can last for clays to lr,eelis, and in some incliviclr-rals, it (lan tal(o years before regaining a for'rer se.se o[.o,'fi*i",r.. irr onc's heartrr. Goiter
The prominent nodltle in the neck can cause lorv self esteen-i because of cosmetic reason o.social stigma. No discrimination in carin-9 these patients is requiled to mirimiTe stigrnatizatior-r.