Dharma Lindarto

Div. Endokrin-MetaboIisme dan Diabetes. Dep IImu

Penyakit DaIam FK USU / RSUP HAM Medan
HYPERTHYRO!D!SN HYPERTHYRO!D!SN
Anatomy of the Thyroid Gland
%iroid Disease
Aspect
fungtion morphology
eutiroid, hypertiroid, hypotiroid
normal, atrophic, nodule, diffus
:lti Nod:le

Hypothalamus Hypothalamus
Pituitary Pituitary Thyroid Axis Thyroid Axis
Typical Thyroid Hormone Levels
in Thyroid Disease
%$ %

Hypothyroidism High Low Low

Hyperthyroidism Low High High
S:-clinical Hypothyroidsm High normal normal
S:-clinical Hyperthyroidsm Low normal normal
Thyrotoxicosis and Hyperthyroidism
Definitions
Thyrotoxicosis
The clinical syndrome of hypermeta-olism that
res:lts when the ser:m concentrations of free
T
4
, T
3
, or -oth are increased
Hyperthyroidism
S:stained increases in thyroid hormone
-iosynthesis and secretion -y the thyroid gland
The 2 terms are not synonymo:s
Braverman LE, et al. Werner & Ingbar's %e %roid. A
Fundamental and Clinical %ext. 8th ed. 2000.
%yroid Storm Rare complication of
hyperthyroidism where manifestations of
thyrotoxicosis -ecome life threatening. Also may -e
termed %yrotoxic Crisis.
Apatetic %yrotoxicosis Rare form :s:ally
occ:rring in the elderly. Often presents as single
organ fail:re (CHF). Patient may develop thyroid
storm witho:t the typical manifestations.
Prevalence of Thyrotoxicosis
n a cross-sectional st:dy of :r-an and
r:ral ad:lts, the prevalence of
thyrotoxicosis ranged from
1.9% to 2.7% in women
0.16% to 0.23% in men
T:n-ridge WG, et al. Clin Endocrinol. 1977;7:481-493.
Hypertyroidism EtioIogy
Graves' disease
MuItinoduIar goiter
Autonomous noduIe
Exogenous tyroid ormone
%ransient-subacute tyroiditis,
postpartum tyroiditis
Drugs-amiodarone
Causes of %yrotoxicosis
Divided by Degree of Radioiodine Uptake
Hig I
123
Uptake
Graves' disease
Toxic nod:lar goiter
TSH-mediated thyrotoxicosis
Pit:itary t:mor
Pit:itary resistance to
thyroid hormone
HCG-mediated thyrotoxicosis
Hydatidiform mole
Choriocarcinoma
Other HCG-secreting t:mors
Thyroid carcinoma (very rare)

ow I
123
Uptake
S:-ac:te thyroiditis
Hashitoxicosis
Dr:g-ind:ced
odide
Thyroid hormone
Str:ma ovarii
Factitio:s

Common Signs and Symptoms

of Thyrotoxicosis
Symptoms Signs
Nervo:sness Hyperactivity
Fatig:e Tachycardia
Weakness Systolic hypertension
ncreased perspiration Warm, moist, or smooth skin
Heat intolerance Stare and eyelid retraction
Tremor Tremor
Hyperactivity Hyperreflexia
Palpitations :scle weakness
Appetite/weight changes
enstr:al dist:r-ances
Braverman LE, et al. Werner & Ingbar's %e %roid. A
Fundamental and Clinical %ext. 8th ed. 2000.
SYSTEC EFFECTS
RESPRATORY
Dyspnea, panting, hyperventalation
respiratory m:scle weakness
increased tiss:e car-on dioxide levels
+/- congestive heart fail:re
SYSTEC EFFECTS
CARDOVASCULAR
Thyrotoxic cardiomyopathy
Hypermeta-olic state
Systemic hypertension
Direct T3 and T4 action on heart
m:scle
LV hypertrophy, VS hypertrophy,
RA and aortic dilation, enhanced
contractility
1. Graves' Disease (Toxic Diff:se Goiter)
The most common ca:se of hyperthyroidism
Acco:nts for 60% to 90% of cases
ncidence in the United States estimated at 0.02% to
0.4% of the pop:lation
Affects more females than males, especially in the
reprod:ctive age range
Graves disease is an a:toimm:ne disorder
possi-ly related to a defect in imm:ne tolerance
Graves Disease
A:toimm:ne disorder
Prod:ction of TSH receptor a:toanti-odies
Stim:late thyroid hormone overprod:ction
Characterized -y the presence of B- and T-
lymphocytes in thyroid tiss:e
TSH receptor activation
Thyroglo-:lin and thyroid peroxidase anti-odies
Sodi:m/iodide cotransporter (NS) activity enhanced
(increased RA)
A:toantigens
A--ott La-oratories Diagnostics Division We- site. Availa-le at: et al. Werner & Ingbar's %e
%roid. A Fundamental and Clinical %ext. 8th ed. 2000.
Graves' Disease
Goiter
Hyperthyroidism
Exophthalmos
Localized myxedema
Thyroid acropachy
Thyroid stimulating immunoglobulins
linical haracteristics of Goiter
in Graves` Disease
Diffuse increase in thyroid gland size
Soft to slightly firm
Non-nodular
Bruit and/or thrill
Mobile
Non-tender
Without prominent adenopathy
Graves` Disease - Localized Myxedema
Margins sharply
demarcated
Thickened skin
Nodularity
Margins sharply
demarcated
Graves' Ophthalmopathy
Class one: spasm of :pper
lids with thyrotoxicosis
Class two: perior-ital edema
and chemosis
Class three: proptosis
Class fo:r: extraoc:lar
m:scle involvement
Class five: corneal
involvement
Class six: loss of vision d:e
to optic nerve involvement
DAGNOSTCS
Endocrine Testing
Total T4: 5-10% will -e normal
Total T3: 30% will -e normal
Free T4: false negative with NT and
shipping
fT4 -etter
T3 s:pression
TRH stim:lation and TSH response
DAGNOSTCS
RADONUCLDE AGNG
Pertechnetate imaging
extent of involvement
detect metastasis to other gland
no palpa-le enlargement (within thorax)
Carcinoma metastasis
2. Toxic :ltinod:lar Goiter
ore common in places with lower iodine
intake
Acco:nts for less than 5% of thyrotoxicosis cases
in iodine-s:fficient areas
Evol:tion from sporadic diff:se goiter to toxic
m:ltinod:lar goiter is grad:al
Thyrotropin receptor m:tations and TSH
m:tations have -een fo:nd in some patients
with toxic m:ltinod:lar goiters
Th/ S:rgery or
131
is recommended treatment
Braverman LE, et al. Werner & Ingbar's %e %roid. A
Fundamental and Clinical %ext. 8th ed. 2000.
Toxic :ltinod:lar Goiter
NG is an enlarged thyroid gland containing
m:ltiple nod:les
The thyroid gland -ecomes more nod:lar with
increasing age
n NG, nod:les typically vary in size
ost NGs are asymptomatic
NG may -e toxic or nontoxic
Toxic NG occ:rs when m:ltiple sites of a:tonomo:s
nod:le hyperf:nction develop, res:lting in
thyrotoxicosis
Toxic NG is more common in the elderly
3. Toxic Adenoma
A:tonomo:sly f:nctioning thyroid
nod:le hypersecreting T3 and T4
res:lting in thyrotoxicosis (Pl:mmer's
disease)
Almost never malignant
anage with antithyroid dr:gs followed
-y either -131 or s:rgery
La-oratory Testing in Thyroid
Disease
TSH:
Pit:itary hormone which stim:lates thyroid
ay rise transiently in recovery from other illness
Free T4:
direct meas:re of thyroxine activity
ay -e transiently s:ppressed in severe ac:te
illness
Free T3: s:spect hyperthyroid -:t normal FT4
Thyroid peroxidase/thyroperoxidase anti-ody:
Anti-TPO
High levels in Hashimoto's (95%) & Graves
TSH receptor stim:lating A- meas:res activity in
Graves-:se in pregnancy
Scans/Ultraso:nd
Radioiodine :ptake (RAU)
Thyroid Scan
Ultraso:nd
Fine needle Aspiration
Treatment of Hyperthyroidism
1. Antithyroid dr:gs
2. S:rgical resection
3. Radioactive iodine therapy
Braverman LE, et al. Werner & Ingbar's %e %roid. A
Fundamental and Clinical %ext. 8th ed. 2000.
1. Antithyroid Dr:g Therapy
Ac:te hyperthyroid symptoms
Goal of therapy:
nhi-it peripheral conversion of T4 to T3
nhi-it synthesis and release of T4 and T3
from thyroid gland
Propylthio:racil (PTU)
ethimazole [generic] or Tapazole
Antithyroid Dr:g Therapy
A. PTU:
nhi-its peripheral conversion of T4 to T3
nhi-its thyroid hormone synthesis and
release from thyroid gland
B. ethimazole [generic]:
nhi-its thyroid hormone synthesis and
release from thyroid gland
C. Beta--locker therapy:
Ameliorates tachycardia, sweating, tremor,
nervo:sness
Propanolol: starting dose 20-40 mg PO
q6h
Ca:tion in patients with CHF or
-ronchospasm
2. S:-total Thyroidectomy
S:rgical complications:
Vocal cord paralysis (1%)
Hypothyroidism (:p to 43% after 10 years)
Hypoparathyroidism
Rec:rrence of hyperthyroidism (10-15%)
3. Radioactive odine
131
[]
A-lation
Treatment of choice in patients > 21
years old with Graves' Disease
Treatment of choice in patients < 21
years old witho:t remission after
antithyroid dr:g therapy
Treatment of choice in patients with
toxic m:ltinod:lar goiter or toxic thyroid
adenoma
Radioactive odine A-lation (cont')
Single dose of
131
[] orally
80% e:thyroid after single dose
> 50% of patients will develop
hypothyroidism
Assay TSH every 3 months after therapy
Radioactive odine A-lation (Cont')
Levothyroxine therapy when patient
-ecomes hypothyroid
Life-long Levothyroxine therapy
RA contraindicated in pregnancy,
lactation, iodine allergy
Screen pre-menopa:sal women for
pregnancy prior to treatment
Thyroid Storm
A life-threatening crisis .
Estimated mortality : 20-30% .
the res:lt of thyroid s:rgery .
Ca:sed more often -y antecedent
Grave's disease .
Precipitants of Thyroid Storm
S:rgery .
Radioiodine therapy .
odinated contrast dyes .
Thyroid hormone ingestion .
Dia-etic Ketoacidosis .
Cere-rovasc:lar accident .
P:lmonary em-olism and CHF .
Pathophysiology of Thyroid
Storm
1) An ac:te decrease in thyroxine-
-inding glo-:lin => high levels of free
hormone .
2) Thyroid hormone increases the
density of -eta-adrenergic receptors &
alters responsiveness to
catecholamines at a postreceptor level .
La-oratory Diagnosis of
Thyroid Storm
A com-ination of low TSH and elevated
free T4 => makes the diagnosis .
f TSH is lower than normal and free T4
is normal => free T3 testing is
recommended .
ED meas:rement of thyroglo-:lin or
thyroid anti-odies : No indication .
Treatment of Thyroid Storm
Block hormone synthesis with either :
a) Propylthio:racil 100-600 mg loading
PO or NG , 200-250 mg q4h for total
daily dose of 1200-1500 mg ; or
-) methimazole 20 mg PO ( 10-40 mg
range ) q 4h .
Treatment of Thyroid Storm
( contin:ed )
nhi-it hormone release :
odides Potassi:m iodide ( SSK ) 5 drops
PO Q6-8H , or
L:gol's sol:tion 7-8 drops ( 1 mL PO Q6H )
or
podate 1-3 g daily ( as 1 g Q8H for 24 ho:rs ,
then 500 mg Q12H ) .
f severe iodide allergy , lithi:m car-onate
300 mg Q6H .
Treatment of Thyroid Storm
( contin:ed )
Gl:cocorticoids : Hydrocortisone ( 300
mg V , then 100 mg V q8h ) ;
dexamethasone ( 2 mg Q6H ) .
Adrenergic -lockade : Propranolol ( 0.5-
3 mg V over 15 min:tes slow V , then
60-80 mg PO Q4H ) ; Esmolol ( 0.25-0.5
mcg/kg loading , inf:sion of 0.05-0.1
mcg/kg/min ) .
Adj:nctive Therapy for
Thyroid Storm
Treat fever aggressively with
acetaminophen .
V fl:id containing 10% dextrose are
recommended .
Administer vitamin s:pplements ,
incl:ding thiamine .
Treat CHF with conventional methods .
Adj:nctive Therapy for
Thyroid Storm ( contin:ed )
dentify the precipitating event ,
incl:ding infection .
Consider plasmapheresis ,
hemodialysis or peritoneal dialysis for
removal of meta-olically active
hormone .
Thyrotoxic Periodic Paralysis
ost common ca:se of hypokalemic periodic
paralysis
Flaccid paralysis
Lower extremities affected most often
Oc:lar and -:l-ar m:scles :ninvolved,
respiratory m:scles rarely involved
ost often starts d:ring sleep
Precipitated following exercise, high salt intake or
high car-ohydrate diet
Hypokalemia d:ring the paralysis
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