1. Dr. W A P S R Weerarathna
Registrar in Medicine-WD 10/02

2.  Hyperthyroidism/Thyrotoxicosis
 Causes ofThyrotoxicosis
 Graves’ disease-Pathology/presentation
 Common/rare complications of Graves’ disease
 Evaluation of a patient with Graves’ disease
 Management of Graves’ disease with recent
advances
 Graves’ opthalmopathy-management
 Graves’ disease in pregnancy
 Summary
 References

3.  Thyrotoxicosis is a syndrome with excess FT4
& FT3
 Hyperthyroidism indicates thyroid gland over
activity resulting in thyrotoxicosis.
 Thyrotoxicosis can result without
hyperthyroidism when stored hormone is
released from damaged thyroid.( subacute
thyroiditis/ excess thyroid hormone ect..)

4. Primary Thyrotoxicosis Secondary hyperth.
hyperthyoridism without hyperthyroidism

5.  Graves disease (commonest cause 70-80%)
 Toxic multinodular goitre
 Toxic adenoma
 Functioning thyroid metastasis
 Struma ovarii-ectopic thyroid tissue
 Activating mutation ofTSH receptor
 Activating mutation of Gsa (McCune-Albright
syndrome)
 Drugs: iodine excess (Jod-Basedow phenomenon)

6.  TSH-secreting pituitary adenoma/TSHoma
 Thyroid hormone resistance syndrome
 Chorionic gonadotropin secreting tumors
 Gestational thyrotoxicosis.
 Testicular malignancies.

7.  Subacute thyroiditis/deQuervain’s/post-
partum
 Silent thyroiditis
 Thyrotoxicosis factitia
 Thyroid destruction: use of amiodarone,
lithium, interferon-alpha & beta, interleukin-
2, radiation & infarction of adenoma

8.  Autoimmune disorder resulting increased
synthesis & release of thyroid hormones
 Female: male= 8:1
 Common among 20-40 years
 Accompanied by infiltrative opthalmopathy in
60% specially in smokers!
 Subclinical opthalmopathy is detected by
CT/MRI.
Infiltrative dermopathy /pretibial myxoedema in
1-2 % over shins, dorsum of foot. (5 P’s)

9.  Thyroid acropatchy- uncommon <1%
resembling finger clubbing & almost
accompanied with opthalmopathy, pretibial
myxoedema
 Painless palpable goitre more than 90% often
with a bruit

10.  Auto Ab’s bind toTSH receptors in thyroid cell
membrane & stimulate the gland to
hyperfuncton-TSI/TSHrAb
 Familial tendency- H/O Graves’ disease or
hashimoto’s thyroiditis
 Associates with HLA-B8 & HLA-DR3
 Thymus gland is typically enlarged & serum ANA
levels usually elevated showing underlying
autoimmunity
 Dietary supplementation can trigger the disease
& treated with amioderone or KI have increased
risk.

11.  Other organ specific autoimmune diseases-
sjogren’s syndrome/celiac disease/pernicious
anemia/Addison’s
disease/vitiligo/T1DM/hypoparathyroidism/
MG/alopecia areata ect…

16.  Opthalmopathy-20-40%
upper eye lid retraction(Dalrymple sign)
lid lag(von Graefe sign)
staring appearance(Kocher sign)
chemosis
conjunctivitis
periorbital edema
proptosis( U/L in 5-10%)
diplopia/extra ocular muscle dysfunction
impaired visual acuity/fields
corneal ulceration
grittiness/increased tear production

17. Exopthalmos/proptosis
Staring appearance

18. Chemosis/periorbital swelling/conjuctivitis

20.  Graves’ dermopathy
glycoaminoglycans/lymphoid infiltration
skin-thickned/rough texture
pre tibial/dorsum of foot
elephantiasis-rare
associated with high levels of
TSI/opthalmopathy

21. Pretibial myxoedema/elephantiasis

22.  Presents with clubbing & swelling of fingers
and toes.
 Periosteal reaction of extremity bones
 Most are smokers!
 Strongly associated with thyroid dermopathy
that an alternative cause of clubbing should
be sought in Graves patient without
coincident skin and orbital involvement.
 Onycholysis/Plummer’s nails

24. clinical
• History and Physical examination.
labs
• Thyroid function test.
• Auto antibodies.
imaging
• Iodine uptake.
• Thyroid USS.

25.  TFT-TSH/FT4 FT3
 Second generation AntiTSH ab ->95% sensitivity
& specificity for diagnosis
 AntiTBG ab/ AntiTPO ab found in up to 80% of
Graves’ disease (also 15 % healthy women & 5%
of men)
 Thyroid scintiscanning withTc 99 /I 131 in doubt
about the nature of the goiter or thyrotoxicosis
without hyperthyroidism is suspected.
 ANA/ds DNA levels are elevated without
evidence of SLE or other ARD’s.

27.  The thyroid gland is diffusely enlarged, and
often homogeneous.
 parenchymal hypervascularity is observed.
 Goiter size is variable,

29.  Carbimazole(CBZ)/methimazole/propylthiour
acil(PTU)
 Inhibits iodine organification by thyroid
peroxidase(TPO), reducingT4 &T3
 PTH- inhibitsT4T3
 Also inhibitsTSI levels accounting for
sustained remission in 40-50% of GD

30.  Titration regimen-initial high doses
 CBZ(40-60mg/d) or PTU(300-450mg/d)
initially/divided doses/3-4 per day
 Tail off every 4-8 weeks based on FT4
 FT4 normalizes-CBZ-once/day with
maintenance dose 5-15mg/day & PTU 50-
150mg/day
 Treat for 18-24 months/monitor FT4 &TSH

31.  Block-replace regimen-CBZ 40mg/d or PTU
300mg/d is maintained throughout
 Hypothyroidism is avoided by givingT4-
addingT4 100mic/d , needed 3-4 wks after
starting.
 T4 dose is adjusted based inT4 levels
 Continued for about 6mths with remission
rate similar to titration regimen!
 Needs few visits/control is smoother
 Only the dose of T4 is altered to optimizeTFT
 NOT used in pregnancy!

32.  Patients are reveiwed regularly in the year
after stopping drugs-70% of relapses!
 Supervenes 15% of autoimmune
hypothyroidism.
 Other drugs- Beta blockers(BB)
 Propanolol 20-40mg/ tds or other non-
selective BB used temporarily in sever
thyrotoxicosis or thyroid crisis.

34. MAJORMINOR
Agranulocytosis (<0.1%) –within 3/12Papular or urticarial skin rashes(1-5%)
Vasculitis (lupus-like syndrome)Arthralgias
PolyarthritisNausea/vomiting
HepatitisPruritis
Cholestatic jaundiceHair loss
Liver failureAbnormal taste sensation
ThrombocytopeniaDrug fever
Stevens-Johnson syndrome *Lymphandenopathy

35.  I 131 concentrates in the thyroid & damage it.
 400-600 MBq, higher doses for larger goitres
 C/I – pregnancy & breast feeding
 Pregnancy is safe after 6 mths/avoid
fathering within 4 mths
 Avoid close contacts with children for several
weeks
 A/E- transient thyroiditis/exacerbation of
thyrotoxicosis/sialoadenitis- occasionally
 ATD’s given before & or shortly after RAI to
prevent thyroid crisis

36.  ATD’s stopped before RAI-CBZ for 2
days/PTU for 2 weeks
 NO overall risk of malignancy after RAI
 RAI acts slowly- wait 4-6 mths before
repeating for persisting thyrotoxicosis
 Transient hypothyroidism within 3 mths/
persistent in about 10% in 1st year
 TFT’s checked annually
 Poor response- large goiter/opthalmopathy

37.  Remove sufficient thyroid tissue-more than
less, hypothyroidism is treatable!
 Recurrence 2-4% in best centers
 Complications(1%) are uncommon-
hypoparathyroidism/RLN
palsy/bleeding/laryngeal edema
 Ensure euthyroidism-avoid crisis-lugol’s
iodine 10 days before surgery to reduce
vascularity & inhibit hormone synthesis

38.  <50 years- initial course of ATD’s vs RAI
 Relapse is treated with RAI or surgery (ATD’s
seldom results in remission!)
 In elderly – indefinite treatment with low dose
ATD’s with risk of recurrence
 >50 years- RAI is the choice!
 RAI may worsens opthalmopathy, specially in
smokers & caution in opthalmopathy
 Try long-term ATD’s/ surgery/RAI combined with
tapering regimen of steroids

39.  Eye discomfort-artificial
rears(day)/oinments(night),glasses
 Periorbital edema-elevate head
end/diuretics(co-amilozide)/radiotheraphy(RT
 Eye protective measures-eye
tapes(night),severe-RT/surgery/corticosteroids
 Congestive opthalmopathy-mild-selenium 100
mic bd
 Severe-high dose prednesolone(40-60mg/d
with tapering or
 IV methylprednesolon pulse theraphy-
500mg/wk for 6wks & 250mg/wk for 6wks

40.  Other immunosupressives-rituximab
 Progressive/active disease-decompressive
surgery or retrobulbar RT
 Optic nerve compression- high dose
prednesols-80-120mg daily with a tapering
regimen.

41.  Lowest possible dose of ATD’s used to maintain
euthyroidism
 Some prefer PTU >CBZ-due to A/E like aplasia
cutis 7 choanal atresia
 Block-replace regimen is C/I- due to insufficient
T4 crossing the placenta & causing neonatal
hypothyroidism
 <5% sufficient maternalTSHRab crossing the
placenta causing fetal & neonatal
hyperthyroidism

42.  Inutero- tachycardia(.160/min) & poor growth
 Can check maternalTSHRab levels inT3
 Mx- ATD’s to mother & monitor fetal
response by cordocentesis samples
 Neonatal hyperthyroidism is self limiting, due
to disappearance of maternalAb’s within
3mths
 BF-possible during ATD’s provided low doses
are used

43.  Thyrotoxicosis is a syndrome caused by
excessive thyroid hormone & is commonly
due to GD
 ATD’s are usually initial treatment of GD &
RAI or surgery being for relapses
 TSHRab’s are sensitive & specific for GD
 RAI in the presence of opthalmopathy should
avoid unless prophylactic CS are given
 Care is needed in managing GD in pregnancy
to avoidA/E for fetus % mother.

44.  Medicine international-vol 41:9 september
2013
 CMDT-2014,1069-1076