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IN THE NAME OF ALLAH,
THE MOST BENEFICIENT ,
THE MOST MERCIFUL .
CASE PRESENTATION:
THYROID EYE DISEASE
• SUPERVISED BY,
DR. WASEEM AHMED KHAN
DOMS,MCPS,FCPS,FRCS(UK)
Assistant Professor MIMC

• PRESENTED BY,
TASHFEEN BASHARAT
HINA BATOOL
RABYIA ASHRAF
BUSHRA ALI
RABIA FAROOQ
ZAKIA SULTANA
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
DEMOGRAPHICS
Name:Imran sharif
Sex:Male
Age:26 yrs
Resident of:Mirpur
Marital status:Married
Education:MBA
Presented to: OPD
PRESENTING COMPLAINTS
• Heaviness and pain in both eyes 2yrs back
• Right sided headache 2yrs back
HISTORY OF PRESENT ILLNESS
• Pt. was in usual state of health 2yrs back when he
gradually developed heaviness and pain in both eyes
with right sided headache in temporal region.After a
couple of weeks he felt bulging of both eyes as well
with bilateral diplopia on side gaze, condition was
progressive in nature , there were no aggrevating &
relieving factors,it was not associated with
redness,discharge,photophobia and change in
vision,he consulted an ophthalmologist at SHIFA
INTERNATIONAL hospital islamabad,where he was
dignosed as a case of proptosis and was prescribed
oral steroids along with topical lubricants
HISTORY OF PRESENTING ILLNESS
• He was also reffered to medical specialist to rule
out thyroid disease as he was also complaining
of frequent vomitting,loss of
appetite,palpitations and diarrhea,where he
was examined and investigated properly.He was
dignosed hyperthyroidism,anti thyroid
treatment was started.He took it for 2yrs but left
it one month ago without the advice of
doctor.Now from last 3 to 4 days he is again
complaining of bulging and pain of both eyes
along with diplopia for which he is taking eye
drops.
PAST OPTHALMIC
HISTORY
PAST OPHTHALMIC HISTORY
• He is myopic from last few years and he is
using spectacles of 1.5 diopters in both eyes
for myopic correction.
• No other significant past ophthalmic history
was found.
SYSTEMIC HISTORY
SYSTEMIC HISTORY
•
•
•
•
•

General health:
Loss of appetite
Loss of weight
Lack of energy
Normal sleep
• CARDIO VASCULAR SYSTEM:
• PALPITATIONS PRESENT
• NO BREATHLESSNESS, CHEST
PAIN AND EDEMA FEET
SYSTEMIC HISTORY
• RESPIRATORY SYSTEM
• No cough, sputum, hemoptysis,
breathlessness, wheezing and chest pain

• ALIMENTARY SYSTEM:
• Vomiting ( containing food particles)
• Diarrhea present
• No nausea, abdominal pain, dysphagia, heart
burn, constipation, hematemesis, melena
and jaundice
SYSTEMIC HISTORY
• URINARY SYSTEM:
• No pain in flanks, dysuria, hematuria,
frequency of micturation, polyuria, oliguria,
nocturia, nausea and vomiting
• NERVOUS SYSTEM:
• Right sided headache in temporal region
• Bilateral Diplopia present on side gaze
• No numbness, giddiness, fits, visual loss
• ENDOCRINE SYSTEM
•
•
•
•

Heat intolerance present
Weight loss present
Palpitations present
No polyuria, polyphagia, polydypsia
• MUSCULOSKELETAL SYSTEM:
no joint pain, stiffness, swelling and
restriction of movment.

• SKIN
• No Rash, itch, coloured spots
PAST MEDICAL & SURGICAL
HISTORY
PAST MEDICAL AND SURGICAL
HISTORY:

Appendisectomy was done at the age
17 yrs.

No other significant past medical and
surgical history .
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
PERSONAL HISTORY:
He is married for last 4 yrs having 2 children
( boys).
HE IS A NON SMOKER.
Not addicted to any drug and his sleep is
normal.
FAMILY HISTORY
FAMILY HISTORY
Father is diabetic for last 20 years
and is taking oral anti diabetic
treatment.
Mother died of heart attack 1 yr
back.
No other family history of Proptosis,
hyper thyriodism, hypertension,
tuberculosis, asthma and cancer
was present.
SOCIOECNOMIC HISTORY
SOCIO ECONOMIC HISTORY:
• He runs his own business( show room of
bikes),
• living in his own house,
• financially stable.
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
Examination
EXAMINATION
• 1) SYSTEMIC

• 2) OCULAR
SYSTEMIC EXAMINATION
• GENERAL PHYSICAL EXAMINATION
• Pateint was sitting comfortably on chair well
oriented in time and space.
•
•
•
•
•

VITALS
Pulse :-120 beats/min
B.P :-120/80 mmHg
Respiratory Rate:- 16breaths/min
Temperature:- 37C
GENERAL PHYSICAL EXAMINATION
• FINGERS
no deformity
• PALM

palmar erythema
+ve
sweating
+ve
GENERAL PHYSICAL EXAMINATION
• FACE
Puffiness
Proptosis
No other deformity

Negative
Positive
THYROID EXAMINATION
•
•
•
•

INSPECTION:
PALPATION:
AUSCULTATION
PEMBERTON SIGN

•
•
•
•

NO VISIBLE SWELLING
NOT PALPABLE
NO BRUIT
ABSENT
GENERAL PHYSICAL EXAMINATION
• Neck veins
No pulsation
JVP normal
• AXILLA
• GROIN
• FEET

Lymph Nodes
Lymph nodes
Clubbing
koilonychnia
cynosis
loss of hair
Edema

not palpable
not palpable

Not Significant
SYSTEMIC EXAMINATION
•
•
•
•

CVS
No significant findings
G.I.T
No significant findings
C.N.S
No significant findings
Respiratory No significant findings
OCULAR EXAMINATION
FUNCTIONAL EXAMINATION :VISUAL ACUITY:
6/18 both eyes with
spectacles 6/6 both
eyes

COLOUR VISION:
normal

VISUAL FIELD:
normal
PROPTOSIS EXAMINATION

• INSPECTION
• Bilateral bulging of eyes( front & side views)
• SWALLOW TEST: NEGATIVE

• PALPATION
• BILATERAL AXIAL PROPTOSIS
4-5 mm in both eyes
• SUPERFICIAL PALPATION:
• NORMAL ORBITAL RIM WITHOUT TENDERNESS
• DEEP PALPATION:
• NO ORBITAL MASS ON DEEP PALPATION
EXAMINATION OF PROPTOSIS
• EXTRA OCULAR
MOVEMENTS
• ABDUCTION & ELEVATION
DEFECIT & DIPLOPIA IN
SIDE GAZE
• RETROPULSION:
POSITIVE IN BOTH EYES
• NO LYMPHYADENOPATHY
IN ADJOINING AREAS

• AUSCULTATION:
• BRUIT: ABSENT
PROPTOSIS EXAMINATION
• Signs checked for bilateral buldging of eyes

• Dalrymples Sign:- +ve
(This is stare due to retraction of upper lid )

• Von Graefes Sign:- +ve
(upper lid lags on downward movement of
eyeball )
OCULAR EXAMINATION
• EYELID
• Skin :- Normal on both sides
• Lid Margin:- BILATERAL Upper lid retracted
•
Bilateral Lid lag
• Eyelashes:- Normal on both sides
• INTER PALPEBRAL FISSURE WIDTH
• Pateint value :- 13mm
• Normal range :- 9-11mm
• LACRIMAL SYSTEM
• Drainage system :-Normal
• Regurgitation test –ve
OCULAR EXAMINATION
•
•
•
•

CONJUCTIVA :- Normal
LIMBUS :- Normal
CORNEA :- Clear
ANTERIOR CHAMBER : Normal
OCULAR EXAMINATION
• IRIS :-Normal
• PUPIL:Round and reactive to light
Diameter :- 3mm
• Light reflex :- Normal
• Indirect light reflex :- normal
• LENS :- clear no opacities found
• VITREOUS :- red reflex was intact
OCULAR EXAMINATION
• RETINA :Slit lamp :- Mild disc
pallor ( both eyes)
MEASUREMENT OF IOP
BY APPLANATION
TONOMETRY
Pateint value :- 16mmHg
both eyes
(Normal 10-21mmHg)
DIFFERENTIAL DIAGNOSIS
• THYROID EYE DISEASE
• IDIOPATHIC ORBITAL INFLAMMATORY
DISEASE
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
INVESTIGATIONS
BASELINE INVESTIGATIONS
• COMPLETE BLOOD PICTURE
• Hb === 12g/dl
• WBC== 8.0 × 10 ( per cubic mm of blood).
• PLATLET COUNT== 274 × 10 ( per cubic mm of
blood)
BASELINE INVESTIGATIONS
• BLOOD SUGAR RANDOM=== 12Omg/dl
• TOTAL CHOLESTROL
=== 167mg/dl
• TRIGLYCERIDE
=== 139mg/dl
THYROID PROFILE
• Following investigations were done for
thyroid function:
• Total T3
• Total T4
• TSH
• Thyroid antibodies
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
OCULAR INVESTIGATIONS
FOLLOWING OCULAR
INVESTIGATIONS WERE DONE:
VISUAL FIELD
OCT
CT SCAN
MRI
VISUAL FEILD
• VISUAL FIELD OF BOTH EYES 30-2 HUM PHRY
WERE DONE WHICH REVEALS NORMAL
VISUAL FIELD IN BOTH EYES.
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
OPTICAL COHERENCE TOMOGRAPHY
(OCT)
SHOWING NORMAL FUNDUS IN BOTH EYES
CT SCAN
FINDINGS
CT—CORONAL VIEW
(showing thickening of extra ocular
muscles)
CT—AXIAL VIEW
{showing enlargement of extraocular muscles
with sparing of tendon (fusiform enlargement)}
CT scan– SAGITTAL VIEW
(showing enlargement of horizontal
extraocular muscles)
MRI ORBIT
• Report verified
thickening of
extraocular
muscles &
enlargement of
soft tissues.
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
MRI – ORBIT
(axial view)
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
TREATMENT
TREATMENT
• Patient was prescribed
=== Anti-thyroid drugs
=== Symptomatic treatment
2 years back
Conservative treatment
• Topical eye drops
== TEARS NATURALE

1 drop 4 times daily
for 2 weeks.
SYMPTOMMATIC TREATMENT
• Tab. BRUFEN (BD)
{for pain}

• Tab. ZANTAC (BD)
{for stomach upset}
ANTI-THYROID THERAPY
• NEO-MERCAZOLE 5mg

• Tab . Propranolol
1 tab daily
Steroid Therapy for ocular soft tissue
inflammation
• Tab. DELTACORTIL 5mg
6- tab in morning
6- tab in evening
For 1 week
TREATMENT…. cont..
• Patient took these medications for almost 2
years with tappered dose but he himself
discontinued the therapy 1 year back.
• Now he is using topical lubricants only.
FUTURE OPTIONS
• In case, the symptoms persist
, treatment option for future
include:
• IMMUNOSUPPRESENTS
• SURGICAL DECOMPRESSION OF
ORBIT
• RADIATION THERAPY
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
THYROID EYE DISEASE
GRAVE’S OPTHALMOPATHY
INTRODUCTION
INTRODUCTION--THYROID EYE
DISEASE
• Seen in 25 – 50% cases of graves disease.
• GRAVES DISEASE also known as BASEDOW’S
DISEASE is an autoimmune disorder that
usually presents in 3rd to 4th decade of life,
affects women more than men, characterized
by a triad of features:
• Hyperthyroidism
• Diffuse thyroid enlargement
• Opthalmopathy
INTRODUCTION -- TED
• Thyroid eye disease (TED) may occur in the
absence of clinical and biochemical evidence
of thyroid dysfunction.
• The occurrence of signs of graves disease in a
patient who is not clinically hyperthyroid is
referred to as euthyroid or ophthalmic graves
disease.
• Eye disease may be the first presenting sign of
graves disease.
ETIOLOGY
==GENETIC FACTOR
ASSOCIATION:
-- HLA DR3, CTLA-4, PTPN22
( a T- cell regulatory gene).
==AUTOIMMUNE DISEASE
ASSOCIATION:
-- Myasthenia gravis,
addison disease.

==RADIOACTIVE THYROID:
Thyroid ablation with orally
ingested radioactive
iodine-131 may excerbate
thyroid associated
orbitopathy compared with
anti-thyroid drugs and
surgical ablation.
•STRONG
ASSOCIATION OF
THYROID EYE
DISEASE WITH
SMOKING
PATHOGENESIS
PATHOGENESIS
• This involves an organ specific autoimmune
reaction in which a humoral agent (IgG antibody)
produces the following changes:

• INFLAMMATION OF EXTRAOCULAR
MUSCLES
• INFLAMMATORY CELLULAR
INFILTRATION
PATHOGENESIS:
INFLAMMATION OF EXTRAOCULAR MUSCLES
• Pleomorphic cellular infiltration, increased secretion
of glycosaminoglycans,osmotic retention of water.
• Muscles become enlarge( 8 times their normal size,
may compress optic nerve).
• Subsequent degeneration of muscle fibers eventually
leads to fibrosis
• Restrictive myopathy and diplopia.
HISTOLOGICAL PICTURE SHOWING ROUND CELL
INFILTRATION OF EXTRA OCULAR MUSCLES IN
THYROID EYE DISEASE
PATHOGENESIS:
INFLAMMATORY CELLULAR INFILTRATION
Infiltration with lymphocytes,
plasma cells, macrophages &
mast cells of interstitial fluid,
orbital fat & lacrimal glands

Increase in volume of
orbital contents

Accumulation of
glycosaminoglycans &
retention of fluid.

Secondary elevation
of intraorbital
pressure.
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
CLINICAL MANIFESTATION
5 main clinical manifestations of TED are:
1… SOFT TISSUE
INVOLVEMENT
(PERIORBITAL & LID SWELLING,
CONJUCTIVAL HYPEREMIA.

2...LID RETRACTION
3…PROPTOSIS
(PASSIVE OR MECHANICAL
PROTRUSION OF EYE BALL)

4…OPTIC NEUROPATHY
(SERIOUS COMPLICATION –
COMPRESSION OF OPTIC NERVE
MAY LEAD TO VISUAL
IMPAIREMENT)

5…RESTRICTIVE
MYOPATHY
(OCULAR MOTILTY IS REDUCED
INITIALLY BY INFLAMMATORY
EDEMA & LATER BY FIBROSIS)
SYMPTOMS
OCULAR SYMPTOMS

SYSTEMIC SYMPTOMS

•
•
•
•
•
•
•

•
•
•
•
•
•
•

DRY EYES
BULGING EYES
DIPLOPIA
VISUAL LOSS
OCULAR PRESSURE OR PAIN
PHOTOPHOBIA
LACRIMATION

TACHYCARDIA
NERVOUSNESS
HEAT INTOLERANCE
INCRESE SWEATING
WEIGHT LOSS
IRRATIBILITY
SKELETAL MUSCLE
WEAKNESS
OCULAR SIGNS
• PROPTOSIS ( eyes protude
beyond orbit…unilateral or
bilateral)
• Exophthlmos (appearance
of protuding eyes)
• Conjuctival edema
• Corneal ulceration
• Visual impairement
• Visual field defects
• Papilloedema
• Loss of colour vision
• Opthlmoplegia
• Optic disc usually normal

•
•
•
•

•
•
•
•
•

VIGOUROUX SIGN( eyelid fullness)
DALRYMPLE SIGN( lid retraction in
primary gaze)
von GRAEFE SIGN( retarted descent
of upper lid at downward gaze
STELLWAG SIGN
( incomplete & infrequent blinking)
GROVE SIGN( resistance to pulling
down the retracted upper lid)
JOFFROY SIGN ( abscent creases in
forehead on sup. gaze)
MOBIUS SIGN( poor convergence)
BALLET SIGN ( restriction of one or
more extra ocular movements)
KOCHER SIGN ( staring & frightened
appearance of eyes)
SEVERE BILATERAL PROPTOSIS & LID
RETRACTION IN THYROID EYE DISEASE
PERIORBITAL SWELLING IN THYROID
EYE DISEASE
LEFT EYE SHOW LID RETRACTION
&MILD PROPTOSIS
von GRAEFE SIGN( RIGHT EYE)
KOCHER SIGN
RESTRICTED LEFT EYE ABDUCTION
SYSTEMIC SIGNS
• FAST/ IRREGULAR
PULSE
• WARM MOIST SKIN
• FINE TREMOR
• PALMER ERYTHEMA
• HAIR LOSS
DIFFERENTIAL
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• ORBITAL CELLULITIS: Onset of proptosis is
earlier & patient has other evidence of
infection. (fever)

• IDIOPATHIC ORBITAL INFLAMMATORY
DISEASE: More painful than thyroid eye
disease.

• OTHER CAUSES OF THICKENED
MUSCLES: sarcoidosis, amyloid, acromegaly.
INVESTIGATIONS
INVESTIGATIONS
NON- SPECIFIC

SPECIFIC

• ROUTINE BLOOD PICTURE.
• HAEMOGLOBIN.
• WBC( total & differential
count.)
• ESR.
• BLOOD SUGAR.
• CHOLESTROL.
• URINE EXAMINATION.

*FOR HYPERTHYROIDISM:
== SERUM T3 & T4 LEVEL
==SERUM TSH LEVEL.
== THYROID AUTOANTIBODIES
*FOR OCULAR MUSCLE
ENLARGEMENT:
==PLAIN X-RAY CALDWELL
VIEW(PA view)
==ORBITAL ULTRASOUND
==CT SCAN ORBIT ( AXIAL &
CORONAL VIEW)
==MRI
Axial CT scan showing enlarged extra
ocular muscles in thyroid eye disease
TREATMENT
GENERAL MANAGMENT
CONTROL OF OCULAR DISCOMFORT
=Artificial tears
=Topical lubricants
=Sunglasses
ADVISE THE PATIENT TO
=Avoid smoking as it worsens the prognosis
=Avoid dust
=Elevate head when sleeping to avoid periorbital
edema
MEDICAL MANAGMENT
CONTROL OF HYPERTHYROIDISM
• Iodine and antithyroid drugs
• Radioactive iodine
ORBITAL DECOMPRESSION
Systemic steroids:
• Oral prednisolone: 60-80mg/day (dose should
be tappered after reduction in symptoms)
• I/V methylprednisolone: 0.5g in 200ml isotonic
saline over 30 min(may be repeated after 48 hrs)
SURGICAL MANAGMENT
Surgical treatment when there is severe sight
threatening condition or for cosmetic purpose.
ORBITAL DECOMPRESSION:
(for advanced proptosis & optic nerve compression)

STRABISMUS SURGERY:
(to minimize diplopia)

LID LENTHENING SURGERY
OTHER MANAGEMENT OPTIONS
RADIOTHERAPY

FUTURE OPTIONS

• ORBITAL RADIOTHERAPY
CAN BE USED TO TREAT
OPHTHALMOPLEGIA BUT
HAS LITTLE EFFECT ON
PROPTOSIS.
• THE RADIATION(1500-2000
Cgy fractioned over 10 days)
IS USUALLY ADMINISTERED
VIA LATERAL FIELDS WITH
POSTERIOR ANGULATION

• ANTI-TNF α
ANTIBODIES(eg infliximab)
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
Prevalence and relative risk of other
autoimmune diseases in subjects with
autoimmune thyroid disease.
• Source
• School of Clinical and Experimental Medicine,
College of Medical and Dental Sciences, Institute
of Biomedical Research, University of
Birmingham, Edgbaston, Birmingham, United
Kingdom. k.boelaert@bham.ac.uk

• BACKGROUND:
• Common autoimmune disorders tend to coexist
in the same subjects and to cluster in families.
METHODS
• A cross-sectional multicenter study of 3286
Caucasian subjects was performed(2791 with
Graves' disease; 495 with Hashimoto's
thyroiditis) attending UK hospital thyroid clinics
to quantify the prevalence of coexisting
autoimmune disorders. All subjects completed a
structured questionnaire seeking a personal and
parental history of common autoimmune
disorders, as well as a history of
hyperthyroidism or hypothyroidism among
parents.
RESULTS
• The frequency of another autoimmune disorder was 9.67%
in Graves' disease and 14.3% in Hashimoto's thyroiditis index
cases . Rheumatoid arthritis was the most common
coexisting autoimmune disorder (found in 3.15% of Graves'
disease and 4.24% of Hashimoto's thyroiditis cases). Relative
risks of almost all other autoimmune diseases in Graves'
disease or Hashimoto's thyroiditis were significantly
increased (>10 for pernicious anemia, systemic lupus
erythematosus, Addison's disease, celiac disease, and
vitiligo). There was relative "clustering" of Graves' disease in
the index case with parental hyperthyroidism and of
Hashimoto's thyroiditis in the index case with parental
hypothyroidism. Relative risks for most other coexisting
autoimmune disorders were markedly increased among
parents of index cases.
CONCLUSION:

• This is one of the largest studies to date to
quantify the risk of diagnosis of coexisting
autoimmune diseases in more than 3000 index
cases with well-characterized Graves' disease or
Hashimoto's thyroiditis. These risks highlight the
importance of screening for other autoimmune
diagnoses if subjects with autoimmune thyroid
disease present with new or nonspecific
symptoms.
References
•

Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a
community: the Whickham survey. Clin Endocrinol (Oxf). 1977;7:481–493

•

Barker JM. Clinical review: type 1 diabetes-associated autoimmunity: natural
history, genetic associations, and screening. J Clin Endocrinol
Metab. 2006;91:1210–1217

•

Tait KF, Marshall T, Berman J, et al. Clustering of autoimmune disease in parents
of siblings from the type 1 diabetes Warren repository. Diabet
Med. 2004;21:358–362

•

Laberge G, Mailloux CM, Gowan K, et al. Early disease onset and increased risk of
other autoimmune diseases in familial generalized vitiligo. Pigment Cell
Res. 2005;18:300–305

•

Kasperlik-Zaluska A, Czarnocka B, Czech W. High prevalence of thyroid
autoimmunity in idiopathic Addison's disease.Autoimmunity. 1994;18:213–216
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
prevalence of patients with
thyroid eye disease
presenting with apparent
unilateral proptosis
• SOURCE:
• Orbital Unit of the Department of Visual Science of the
University of Naples “Federico II”
• AIMS & OBJECTIVES:
• The purpose of this retrospective follow-up study is to
evaluate the prevalence of patients with thyroid eye
disease presenting with apparent unilateral proptosis
and determine the occurrence of exophthalmos in
contralateral non-proptotic eye over the time.
Associated features with this event were evaluated.
Methods
• A cohort of 655 consecutive patients affected
by thyroid eye disease with a minimum
follow-up of 10 years was reviewed.
Exophthalmos was assessed by using both
Hertel exophthalmometer and computed
tomography (CT). The influence of
age, gender, hormonal status and of different
therapies such as
corticosteroids, radiotherapy and surgical
decompression on this disease progression
Results
• A total of 89 patients (13.5%) had clinical
evidence of unilateral exophthalmos at the first
visit. Among these, 13 patients (14%)
developed subsequent contralateral
exophthalmos. The increase of protrusion
ranged from 2 to 7 mm (mean of 4.2). The time
of onset varied from 6 months to 7 years (mean
time: 29 months). Smoking status, young age
and surgical decompression are significantly
associated with development of contralateral
proptosis .
Conclusions
• Asymmetric thyroid eye disease with the
appearance of unilateral exophthalmos at the
initial examination is a fairly frequent event,
while subsequent contralateral proptosis
occurs less commonly. However, physicians
should be aware that young patients,
particularly if smokers, undergoing orbital
decompression in one eye may need further
surgery on contralateral side over time.
• References
•

Burch HB, Wartofsky L: Graves’ ophthalmopathy: current concepts regarding pathogenesis
and management.

•
•

Hales IB, Rundle FF: Ocular changes in Graves' disease: a long-term follow-up study.
Q J Med 1960, 29:113.

•
•

Gerding MN, Terwee CB, Dekker FW: Quality of life in patients with Graves’ ophthalmopathy
is markedly decreased: measurement by the medical outcomes study instrument.
Thyroid 1997, 7:885-889.

•
•

Bahn RS, Heufelder AE: Pathogenesis of Graves’ ophthalmopathy.
N Engl J Med 1993, 329:1468-1475.

•
•

Gorman CA: Pathogenesis of Graves’ ophthalmopathy.
Thyroid 1994, 4:

•
•

Heufelder AE: Pathogenesis of Graves’ ophthalmopathy: recent controversies and progress.
Eur J Endocrinol 1995, 132:
CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease

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CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease

  • 1. IN THE NAME OF ALLAH, THE MOST BENEFICIENT , THE MOST MERCIFUL .
  • 2. CASE PRESENTATION: THYROID EYE DISEASE • SUPERVISED BY, DR. WASEEM AHMED KHAN DOMS,MCPS,FCPS,FRCS(UK) Assistant Professor MIMC • PRESENTED BY, TASHFEEN BASHARAT HINA BATOOL RABYIA ASHRAF BUSHRA ALI RABIA FAROOQ ZAKIA SULTANA
  • 4. DEMOGRAPHICS Name:Imran sharif Sex:Male Age:26 yrs Resident of:Mirpur Marital status:Married Education:MBA Presented to: OPD
  • 5. PRESENTING COMPLAINTS • Heaviness and pain in both eyes 2yrs back • Right sided headache 2yrs back
  • 6. HISTORY OF PRESENT ILLNESS • Pt. was in usual state of health 2yrs back when he gradually developed heaviness and pain in both eyes with right sided headache in temporal region.After a couple of weeks he felt bulging of both eyes as well with bilateral diplopia on side gaze, condition was progressive in nature , there were no aggrevating & relieving factors,it was not associated with redness,discharge,photophobia and change in vision,he consulted an ophthalmologist at SHIFA INTERNATIONAL hospital islamabad,where he was dignosed as a case of proptosis and was prescribed oral steroids along with topical lubricants
  • 7. HISTORY OF PRESENTING ILLNESS • He was also reffered to medical specialist to rule out thyroid disease as he was also complaining of frequent vomitting,loss of appetite,palpitations and diarrhea,where he was examined and investigated properly.He was dignosed hyperthyroidism,anti thyroid treatment was started.He took it for 2yrs but left it one month ago without the advice of doctor.Now from last 3 to 4 days he is again complaining of bulging and pain of both eyes along with diplopia for which he is taking eye drops.
  • 9. PAST OPHTHALMIC HISTORY • He is myopic from last few years and he is using spectacles of 1.5 diopters in both eyes for myopic correction. • No other significant past ophthalmic history was found.
  • 11. SYSTEMIC HISTORY • • • • • General health: Loss of appetite Loss of weight Lack of energy Normal sleep
  • 12. • CARDIO VASCULAR SYSTEM: • PALPITATIONS PRESENT • NO BREATHLESSNESS, CHEST PAIN AND EDEMA FEET
  • 13. SYSTEMIC HISTORY • RESPIRATORY SYSTEM • No cough, sputum, hemoptysis, breathlessness, wheezing and chest pain • ALIMENTARY SYSTEM: • Vomiting ( containing food particles) • Diarrhea present • No nausea, abdominal pain, dysphagia, heart burn, constipation, hematemesis, melena and jaundice
  • 14. SYSTEMIC HISTORY • URINARY SYSTEM: • No pain in flanks, dysuria, hematuria, frequency of micturation, polyuria, oliguria, nocturia, nausea and vomiting • NERVOUS SYSTEM: • Right sided headache in temporal region • Bilateral Diplopia present on side gaze • No numbness, giddiness, fits, visual loss
  • 15. • ENDOCRINE SYSTEM • • • • Heat intolerance present Weight loss present Palpitations present No polyuria, polyphagia, polydypsia • MUSCULOSKELETAL SYSTEM: no joint pain, stiffness, swelling and restriction of movment. • SKIN • No Rash, itch, coloured spots
  • 16. PAST MEDICAL & SURGICAL HISTORY
  • 17. PAST MEDICAL AND SURGICAL HISTORY: Appendisectomy was done at the age 17 yrs. No other significant past medical and surgical history .
  • 19. PERSONAL HISTORY: He is married for last 4 yrs having 2 children ( boys). HE IS A NON SMOKER. Not addicted to any drug and his sleep is normal.
  • 21. FAMILY HISTORY Father is diabetic for last 20 years and is taking oral anti diabetic treatment. Mother died of heart attack 1 yr back. No other family history of Proptosis, hyper thyriodism, hypertension, tuberculosis, asthma and cancer was present.
  • 23. SOCIO ECONOMIC HISTORY: • He runs his own business( show room of bikes), • living in his own house, • financially stable.
  • 27. SYSTEMIC EXAMINATION • GENERAL PHYSICAL EXAMINATION • Pateint was sitting comfortably on chair well oriented in time and space. • • • • • VITALS Pulse :-120 beats/min B.P :-120/80 mmHg Respiratory Rate:- 16breaths/min Temperature:- 37C
  • 28. GENERAL PHYSICAL EXAMINATION • FINGERS no deformity • PALM palmar erythema +ve sweating +ve
  • 29. GENERAL PHYSICAL EXAMINATION • FACE Puffiness Proptosis No other deformity Negative Positive
  • 31. GENERAL PHYSICAL EXAMINATION • Neck veins No pulsation JVP normal • AXILLA • GROIN • FEET Lymph Nodes Lymph nodes Clubbing koilonychnia cynosis loss of hair Edema not palpable not palpable Not Significant
  • 32. SYSTEMIC EXAMINATION • • • • CVS No significant findings G.I.T No significant findings C.N.S No significant findings Respiratory No significant findings
  • 34. FUNCTIONAL EXAMINATION :VISUAL ACUITY: 6/18 both eyes with spectacles 6/6 both eyes COLOUR VISION: normal VISUAL FIELD: normal
  • 35. PROPTOSIS EXAMINATION • INSPECTION • Bilateral bulging of eyes( front & side views) • SWALLOW TEST: NEGATIVE • PALPATION • BILATERAL AXIAL PROPTOSIS 4-5 mm in both eyes • SUPERFICIAL PALPATION: • NORMAL ORBITAL RIM WITHOUT TENDERNESS • DEEP PALPATION: • NO ORBITAL MASS ON DEEP PALPATION
  • 36. EXAMINATION OF PROPTOSIS • EXTRA OCULAR MOVEMENTS • ABDUCTION & ELEVATION DEFECIT & DIPLOPIA IN SIDE GAZE • RETROPULSION: POSITIVE IN BOTH EYES • NO LYMPHYADENOPATHY IN ADJOINING AREAS • AUSCULTATION: • BRUIT: ABSENT
  • 37. PROPTOSIS EXAMINATION • Signs checked for bilateral buldging of eyes • Dalrymples Sign:- +ve (This is stare due to retraction of upper lid ) • Von Graefes Sign:- +ve (upper lid lags on downward movement of eyeball )
  • 38. OCULAR EXAMINATION • EYELID • Skin :- Normal on both sides • Lid Margin:- BILATERAL Upper lid retracted • Bilateral Lid lag • Eyelashes:- Normal on both sides • INTER PALPEBRAL FISSURE WIDTH • Pateint value :- 13mm • Normal range :- 9-11mm • LACRIMAL SYSTEM • Drainage system :-Normal • Regurgitation test –ve
  • 39. OCULAR EXAMINATION • • • • CONJUCTIVA :- Normal LIMBUS :- Normal CORNEA :- Clear ANTERIOR CHAMBER : Normal
  • 40. OCULAR EXAMINATION • IRIS :-Normal • PUPIL:Round and reactive to light Diameter :- 3mm • Light reflex :- Normal • Indirect light reflex :- normal • LENS :- clear no opacities found • VITREOUS :- red reflex was intact
  • 41. OCULAR EXAMINATION • RETINA :Slit lamp :- Mild disc pallor ( both eyes) MEASUREMENT OF IOP BY APPLANATION TONOMETRY Pateint value :- 16mmHg both eyes (Normal 10-21mmHg)
  • 42. DIFFERENTIAL DIAGNOSIS • THYROID EYE DISEASE • IDIOPATHIC ORBITAL INFLAMMATORY DISEASE
  • 45. BASELINE INVESTIGATIONS • COMPLETE BLOOD PICTURE • Hb === 12g/dl • WBC== 8.0 × 10 ( per cubic mm of blood). • PLATLET COUNT== 274 × 10 ( per cubic mm of blood)
  • 46. BASELINE INVESTIGATIONS • BLOOD SUGAR RANDOM=== 12Omg/dl • TOTAL CHOLESTROL === 167mg/dl • TRIGLYCERIDE === 139mg/dl
  • 47. THYROID PROFILE • Following investigations were done for thyroid function: • Total T3 • Total T4 • TSH • Thyroid antibodies
  • 50. OCULAR INVESTIGATIONS FOLLOWING OCULAR INVESTIGATIONS WERE DONE: VISUAL FIELD OCT CT SCAN MRI
  • 51. VISUAL FEILD • VISUAL FIELD OF BOTH EYES 30-2 HUM PHRY WERE DONE WHICH REVEALS NORMAL VISUAL FIELD IN BOTH EYES.
  • 54. OPTICAL COHERENCE TOMOGRAPHY (OCT) SHOWING NORMAL FUNDUS IN BOTH EYES
  • 56. CT—CORONAL VIEW (showing thickening of extra ocular muscles)
  • 57. CT—AXIAL VIEW {showing enlargement of extraocular muscles with sparing of tendon (fusiform enlargement)}
  • 58. CT scan– SAGITTAL VIEW (showing enlargement of horizontal extraocular muscles)
  • 59. MRI ORBIT • Report verified thickening of extraocular muscles & enlargement of soft tissues.
  • 64. TREATMENT • Patient was prescribed === Anti-thyroid drugs === Symptomatic treatment 2 years back
  • 65. Conservative treatment • Topical eye drops == TEARS NATURALE 1 drop 4 times daily for 2 weeks.
  • 66. SYMPTOMMATIC TREATMENT • Tab. BRUFEN (BD) {for pain} • Tab. ZANTAC (BD) {for stomach upset}
  • 67. ANTI-THYROID THERAPY • NEO-MERCAZOLE 5mg • Tab . Propranolol 1 tab daily
  • 68. Steroid Therapy for ocular soft tissue inflammation • Tab. DELTACORTIL 5mg 6- tab in morning 6- tab in evening For 1 week
  • 69. TREATMENT…. cont.. • Patient took these medications for almost 2 years with tappered dose but he himself discontinued the therapy 1 year back. • Now he is using topical lubricants only.
  • 70. FUTURE OPTIONS • In case, the symptoms persist , treatment option for future include: • IMMUNOSUPPRESENTS • SURGICAL DECOMPRESSION OF ORBIT • RADIATION THERAPY
  • 74. INTRODUCTION--THYROID EYE DISEASE • Seen in 25 – 50% cases of graves disease. • GRAVES DISEASE also known as BASEDOW’S DISEASE is an autoimmune disorder that usually presents in 3rd to 4th decade of life, affects women more than men, characterized by a triad of features: • Hyperthyroidism • Diffuse thyroid enlargement • Opthalmopathy
  • 75. INTRODUCTION -- TED • Thyroid eye disease (TED) may occur in the absence of clinical and biochemical evidence of thyroid dysfunction. • The occurrence of signs of graves disease in a patient who is not clinically hyperthyroid is referred to as euthyroid or ophthalmic graves disease. • Eye disease may be the first presenting sign of graves disease.
  • 77. ==GENETIC FACTOR ASSOCIATION: -- HLA DR3, CTLA-4, PTPN22 ( a T- cell regulatory gene). ==AUTOIMMUNE DISEASE ASSOCIATION: -- Myasthenia gravis, addison disease. ==RADIOACTIVE THYROID: Thyroid ablation with orally ingested radioactive iodine-131 may excerbate thyroid associated orbitopathy compared with anti-thyroid drugs and surgical ablation.
  • 80. PATHOGENESIS • This involves an organ specific autoimmune reaction in which a humoral agent (IgG antibody) produces the following changes: • INFLAMMATION OF EXTRAOCULAR MUSCLES • INFLAMMATORY CELLULAR INFILTRATION
  • 81. PATHOGENESIS: INFLAMMATION OF EXTRAOCULAR MUSCLES • Pleomorphic cellular infiltration, increased secretion of glycosaminoglycans,osmotic retention of water. • Muscles become enlarge( 8 times their normal size, may compress optic nerve). • Subsequent degeneration of muscle fibers eventually leads to fibrosis • Restrictive myopathy and diplopia.
  • 82. HISTOLOGICAL PICTURE SHOWING ROUND CELL INFILTRATION OF EXTRA OCULAR MUSCLES IN THYROID EYE DISEASE
  • 83. PATHOGENESIS: INFLAMMATORY CELLULAR INFILTRATION Infiltration with lymphocytes, plasma cells, macrophages & mast cells of interstitial fluid, orbital fat & lacrimal glands Increase in volume of orbital contents Accumulation of glycosaminoglycans & retention of fluid. Secondary elevation of intraorbital pressure.
  • 85. CLINICAL MANIFESTATION 5 main clinical manifestations of TED are: 1… SOFT TISSUE INVOLVEMENT (PERIORBITAL & LID SWELLING, CONJUCTIVAL HYPEREMIA. 2...LID RETRACTION 3…PROPTOSIS (PASSIVE OR MECHANICAL PROTRUSION OF EYE BALL) 4…OPTIC NEUROPATHY (SERIOUS COMPLICATION – COMPRESSION OF OPTIC NERVE MAY LEAD TO VISUAL IMPAIREMENT) 5…RESTRICTIVE MYOPATHY (OCULAR MOTILTY IS REDUCED INITIALLY BY INFLAMMATORY EDEMA & LATER BY FIBROSIS)
  • 86. SYMPTOMS OCULAR SYMPTOMS SYSTEMIC SYMPTOMS • • • • • • • • • • • • • • DRY EYES BULGING EYES DIPLOPIA VISUAL LOSS OCULAR PRESSURE OR PAIN PHOTOPHOBIA LACRIMATION TACHYCARDIA NERVOUSNESS HEAT INTOLERANCE INCRESE SWEATING WEIGHT LOSS IRRATIBILITY SKELETAL MUSCLE WEAKNESS
  • 87. OCULAR SIGNS • PROPTOSIS ( eyes protude beyond orbit…unilateral or bilateral) • Exophthlmos (appearance of protuding eyes) • Conjuctival edema • Corneal ulceration • Visual impairement • Visual field defects • Papilloedema • Loss of colour vision • Opthlmoplegia • Optic disc usually normal • • • • • • • • • VIGOUROUX SIGN( eyelid fullness) DALRYMPLE SIGN( lid retraction in primary gaze) von GRAEFE SIGN( retarted descent of upper lid at downward gaze STELLWAG SIGN ( incomplete & infrequent blinking) GROVE SIGN( resistance to pulling down the retracted upper lid) JOFFROY SIGN ( abscent creases in forehead on sup. gaze) MOBIUS SIGN( poor convergence) BALLET SIGN ( restriction of one or more extra ocular movements) KOCHER SIGN ( staring & frightened appearance of eyes)
  • 88. SEVERE BILATERAL PROPTOSIS & LID RETRACTION IN THYROID EYE DISEASE
  • 89. PERIORBITAL SWELLING IN THYROID EYE DISEASE
  • 90. LEFT EYE SHOW LID RETRACTION &MILD PROPTOSIS
  • 91. von GRAEFE SIGN( RIGHT EYE)
  • 93. RESTRICTED LEFT EYE ABDUCTION
  • 94. SYSTEMIC SIGNS • FAST/ IRREGULAR PULSE • WARM MOIST SKIN • FINE TREMOR • PALMER ERYTHEMA • HAIR LOSS
  • 96. DIFFERENTIAL DIAGNOSIS • ORBITAL CELLULITIS: Onset of proptosis is earlier & patient has other evidence of infection. (fever) • IDIOPATHIC ORBITAL INFLAMMATORY DISEASE: More painful than thyroid eye disease. • OTHER CAUSES OF THICKENED MUSCLES: sarcoidosis, amyloid, acromegaly.
  • 98. INVESTIGATIONS NON- SPECIFIC SPECIFIC • ROUTINE BLOOD PICTURE. • HAEMOGLOBIN. • WBC( total & differential count.) • ESR. • BLOOD SUGAR. • CHOLESTROL. • URINE EXAMINATION. *FOR HYPERTHYROIDISM: == SERUM T3 & T4 LEVEL ==SERUM TSH LEVEL. == THYROID AUTOANTIBODIES *FOR OCULAR MUSCLE ENLARGEMENT: ==PLAIN X-RAY CALDWELL VIEW(PA view) ==ORBITAL ULTRASOUND ==CT SCAN ORBIT ( AXIAL & CORONAL VIEW) ==MRI
  • 99. Axial CT scan showing enlarged extra ocular muscles in thyroid eye disease
  • 101. GENERAL MANAGMENT CONTROL OF OCULAR DISCOMFORT =Artificial tears =Topical lubricants =Sunglasses ADVISE THE PATIENT TO =Avoid smoking as it worsens the prognosis =Avoid dust =Elevate head when sleeping to avoid periorbital edema
  • 102. MEDICAL MANAGMENT CONTROL OF HYPERTHYROIDISM • Iodine and antithyroid drugs • Radioactive iodine ORBITAL DECOMPRESSION Systemic steroids: • Oral prednisolone: 60-80mg/day (dose should be tappered after reduction in symptoms) • I/V methylprednisolone: 0.5g in 200ml isotonic saline over 30 min(may be repeated after 48 hrs)
  • 103. SURGICAL MANAGMENT Surgical treatment when there is severe sight threatening condition or for cosmetic purpose. ORBITAL DECOMPRESSION: (for advanced proptosis & optic nerve compression) STRABISMUS SURGERY: (to minimize diplopia) LID LENTHENING SURGERY
  • 104. OTHER MANAGEMENT OPTIONS RADIOTHERAPY FUTURE OPTIONS • ORBITAL RADIOTHERAPY CAN BE USED TO TREAT OPHTHALMOPLEGIA BUT HAS LITTLE EFFECT ON PROPTOSIS. • THE RADIATION(1500-2000 Cgy fractioned over 10 days) IS USUALLY ADMINISTERED VIA LATERAL FIELDS WITH POSTERIOR ANGULATION • ANTI-TNF α ANTIBODIES(eg infliximab)
  • 108. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease.
  • 109. • Source • School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, United Kingdom. k.boelaert@bham.ac.uk • BACKGROUND: • Common autoimmune disorders tend to coexist in the same subjects and to cluster in families.
  • 110. METHODS • A cross-sectional multicenter study of 3286 Caucasian subjects was performed(2791 with Graves' disease; 495 with Hashimoto's thyroiditis) attending UK hospital thyroid clinics to quantify the prevalence of coexisting autoimmune disorders. All subjects completed a structured questionnaire seeking a personal and parental history of common autoimmune disorders, as well as a history of hyperthyroidism or hypothyroidism among parents.
  • 111. RESULTS • The frequency of another autoimmune disorder was 9.67% in Graves' disease and 14.3% in Hashimoto's thyroiditis index cases . Rheumatoid arthritis was the most common coexisting autoimmune disorder (found in 3.15% of Graves' disease and 4.24% of Hashimoto's thyroiditis cases). Relative risks of almost all other autoimmune diseases in Graves' disease or Hashimoto's thyroiditis were significantly increased (>10 for pernicious anemia, systemic lupus erythematosus, Addison's disease, celiac disease, and vitiligo). There was relative "clustering" of Graves' disease in the index case with parental hyperthyroidism and of Hashimoto's thyroiditis in the index case with parental hypothyroidism. Relative risks for most other coexisting autoimmune disorders were markedly increased among parents of index cases.
  • 112. CONCLUSION: • This is one of the largest studies to date to quantify the risk of diagnosis of coexisting autoimmune diseases in more than 3000 index cases with well-characterized Graves' disease or Hashimoto's thyroiditis. These risks highlight the importance of screening for other autoimmune diagnoses if subjects with autoimmune thyroid disease present with new or nonspecific symptoms.
  • 113. References • Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977;7:481–493 • Barker JM. Clinical review: type 1 diabetes-associated autoimmunity: natural history, genetic associations, and screening. J Clin Endocrinol Metab. 2006;91:1210–1217 • Tait KF, Marshall T, Berman J, et al. Clustering of autoimmune disease in parents of siblings from the type 1 diabetes Warren repository. Diabet Med. 2004;21:358–362 • Laberge G, Mailloux CM, Gowan K, et al. Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo. Pigment Cell Res. 2005;18:300–305 • Kasperlik-Zaluska A, Czarnocka B, Czech W. High prevalence of thyroid autoimmunity in idiopathic Addison's disease.Autoimmunity. 1994;18:213–216
  • 115. prevalence of patients with thyroid eye disease presenting with apparent unilateral proptosis
  • 116. • SOURCE: • Orbital Unit of the Department of Visual Science of the University of Naples “Federico II” • AIMS & OBJECTIVES: • The purpose of this retrospective follow-up study is to evaluate the prevalence of patients with thyroid eye disease presenting with apparent unilateral proptosis and determine the occurrence of exophthalmos in contralateral non-proptotic eye over the time. Associated features with this event were evaluated.
  • 117. Methods • A cohort of 655 consecutive patients affected by thyroid eye disease with a minimum follow-up of 10 years was reviewed. Exophthalmos was assessed by using both Hertel exophthalmometer and computed tomography (CT). The influence of age, gender, hormonal status and of different therapies such as corticosteroids, radiotherapy and surgical decompression on this disease progression
  • 118. Results • A total of 89 patients (13.5%) had clinical evidence of unilateral exophthalmos at the first visit. Among these, 13 patients (14%) developed subsequent contralateral exophthalmos. The increase of protrusion ranged from 2 to 7 mm (mean of 4.2). The time of onset varied from 6 months to 7 years (mean time: 29 months). Smoking status, young age and surgical decompression are significantly associated with development of contralateral proptosis .
  • 119. Conclusions • Asymmetric thyroid eye disease with the appearance of unilateral exophthalmos at the initial examination is a fairly frequent event, while subsequent contralateral proptosis occurs less commonly. However, physicians should be aware that young patients, particularly if smokers, undergoing orbital decompression in one eye may need further surgery on contralateral side over time.
  • 120. • References • Burch HB, Wartofsky L: Graves’ ophthalmopathy: current concepts regarding pathogenesis and management. • • Hales IB, Rundle FF: Ocular changes in Graves' disease: a long-term follow-up study. Q J Med 1960, 29:113. • • Gerding MN, Terwee CB, Dekker FW: Quality of life in patients with Graves’ ophthalmopathy is markedly decreased: measurement by the medical outcomes study instrument. Thyroid 1997, 7:885-889. • • Bahn RS, Heufelder AE: Pathogenesis of Graves’ ophthalmopathy. N Engl J Med 1993, 329:1468-1475. • • Gorman CA: Pathogenesis of Graves’ ophthalmopathy. Thyroid 1994, 4: • • Heufelder AE: Pathogenesis of Graves’ ophthalmopathy: recent controversies and progress. Eur J Endocrinol 1995, 132: