This document discusses Graves' disease, a common cause of hyperthyroidism. It covers the pathogenesis, presentation, evaluation and management of Graves' disease. Key points include: Graves' disease is an autoimmune disorder causing hyperthyroidism in 70-80% of cases. It presents with a diffuse goiter and may involve the eyes or skin. Evaluation involves thyroid function tests and autoantibody tests. Management involves antithyroid medications like carbimazole or propylthiouracil. Radioactive iodine or surgery are options for relapses or non-responders. Care must be taken in managing Graves' disease during pregnancy to avoid complications for the mother and fetus.

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