CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease
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CLINICOPATHOLOGICAL CONFERENCE ON Thyroid eye disease

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  • 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
  • 3. DEMOGRAPHICS Name:Imran sharif Sex:Male Age:26 yrs Resident of:Mirpur Marital status:Married Education:MBA Presented to: OPD
  • 4. PRESENTING COMPLAINTS • Heaviness and pain in both eyes 2yrs back • Right sided headache 2yrs back
  • 5. 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
  • 6. 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.
  • 7. PAST OPTHALMIC HISTORY
  • 8. 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.
  • 9. SYSTEMIC HISTORY
  • 10. SYSTEMIC HISTORY • • • • • General health: Loss of appetite Loss of weight Lack of energy Normal sleep
  • 11. • CARDIO VASCULAR SYSTEM: • PALPITATIONS PRESENT • NO BREATHLESSNESS, CHEST PAIN AND EDEMA FEET
  • 12. 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
  • 13. 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
  • 14. • 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
  • 15. PAST MEDICAL & SURGICAL HISTORY
  • 16. PAST MEDICAL AND SURGICAL HISTORY: Appendisectomy was done at the age 17 yrs. No other significant past medical and surgical history .
  • 17. 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.
  • 18. FAMILY HISTORY
  • 19. 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.
  • 20. SOCIOECNOMIC HISTORY
  • 21. SOCIO ECONOMIC HISTORY: • He runs his own business( show room of bikes), • living in his own house, • financially stable.
  • 22. Examination
  • 23. EXAMINATION • 1) SYSTEMIC • 2) OCULAR
  • 24. 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
  • 25. GENERAL PHYSICAL EXAMINATION • FINGERS no deformity • PALM palmar erythema +ve sweating +ve
  • 26. GENERAL PHYSICAL EXAMINATION • FACE Puffiness Proptosis No other deformity Negative Positive
  • 27. THYROID EXAMINATION • • • • INSPECTION: PALPATION: AUSCULTATION PEMBERTON SIGN • • • • NO VISIBLE SWELLING NOT PALPABLE NO BRUIT ABSENT
  • 28. 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
  • 29. SYSTEMIC EXAMINATION • • • • CVS No significant findings G.I.T No significant findings C.N.S No significant findings Respiratory No significant findings
  • 30. OCULAR EXAMINATION
  • 31. FUNCTIONAL EXAMINATION :VISUAL ACUITY: 6/18 both eyes with spectacles 6/6 both eyes COLOUR VISION: normal VISUAL FIELD: normal
  • 32. 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
  • 33. 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
  • 34. 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 )
  • 35. 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
  • 36. OCULAR EXAMINATION • • • • CONJUCTIVA :- Normal LIMBUS :- Normal CORNEA :- Clear ANTERIOR CHAMBER : Normal
  • 37. 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
  • 38. OCULAR EXAMINATION • RETINA :Slit lamp :- Mild disc pallor ( both eyes) MEASUREMENT OF IOP BY APPLANATION TONOMETRY Pateint value :- 16mmHg both eyes (Normal 10-21mmHg)
  • 39. DIFFERENTIAL DIAGNOSIS • THYROID EYE DISEASE • IDIOPATHIC ORBITAL INFLAMMATORY DISEASE
  • 40. INVESTIGATIONS
  • 41. 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)
  • 42. BASELINE INVESTIGATIONS • BLOOD SUGAR RANDOM=== 12Omg/dl • TOTAL CHOLESTROL === 167mg/dl • TRIGLYCERIDE === 139mg/dl
  • 43. THYROID PROFILE • Following investigations were done for thyroid function: • Total T3 • Total T4 • TSH • Thyroid antibodies
  • 44. OCULAR INVESTIGATIONS FOLLOWING OCULAR INVESTIGATIONS WERE DONE: VISUAL FIELD OCT CT SCAN MRI
  • 45. VISUAL FEILD • VISUAL FIELD OF BOTH EYES 30-2 HUM PHRY WERE DONE WHICH REVEALS NORMAL VISUAL FIELD IN BOTH EYES.
  • 46. OPTICAL COHERENCE TOMOGRAPHY (OCT) SHOWING NORMAL FUNDUS IN BOTH EYES
  • 47. CT SCAN FINDINGS
  • 48. CT—CORONAL VIEW (showing thickening of extra ocular muscles)
  • 49. CT—AXIAL VIEW {showing enlargement of extraocular muscles with sparing of tendon (fusiform enlargement)}
  • 50. CT scan– SAGITTAL VIEW (showing enlargement of horizontal extraocular muscles)
  • 51. MRI ORBIT • Report verified thickening of extraocular muscles & enlargement of soft tissues.
  • 52. MRI – ORBIT (axial view)
  • 53. TREATMENT
  • 54. TREATMENT • Patient was prescribed === Anti-thyroid drugs === Symptomatic treatment 2 years back
  • 55. Conservative treatment • Topical eye drops == TEARS NATURALE 1 drop 4 times daily for 2 weeks.
  • 56. SYMPTOMMATIC TREATMENT • Tab. BRUFEN (BD) {for pain} • Tab. ZANTAC (BD) {for stomach upset}
  • 57. ANTI-THYROID THERAPY • NEO-MERCAZOLE 5mg • Tab . Propranolol 1 tab daily
  • 58. Steroid Therapy for ocular soft tissue inflammation • Tab. DELTACORTIL 5mg 6- tab in morning 6- tab in evening For 1 week
  • 59. 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.
  • 60. FUTURE OPTIONS • In case, the symptoms persist , treatment option for future include: • IMMUNOSUPPRESENTS • SURGICAL DECOMPRESSION OF ORBIT • RADIATION THERAPY
  • 61. THYROID EYE DISEASE GRAVE’S OPTHALMOPATHY
  • 62. INTRODUCTION
  • 63. 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
  • 64. 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.
  • 65. ETIOLOGY
  • 66. ==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.
  • 67. •STRONG ASSOCIATION OF THYROID EYE DISEASE WITH SMOKING
  • 68. PATHOGENESIS
  • 69. 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
  • 70. 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.
  • 71. HISTOLOGICAL PICTURE SHOWING ROUND CELL INFILTRATION OF EXTRA OCULAR MUSCLES IN THYROID EYE DISEASE
  • 72. 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.
  • 73. 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)
  • 74. 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
  • 75. 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)
  • 76. SEVERE BILATERAL PROPTOSIS & LID RETRACTION IN THYROID EYE DISEASE
  • 77. PERIORBITAL SWELLING IN THYROID EYE DISEASE
  • 78. LEFT EYE SHOW LID RETRACTION &MILD PROPTOSIS
  • 79. von GRAEFE SIGN( RIGHT EYE)
  • 80. KOCHER SIGN
  • 81. RESTRICTED LEFT EYE ABDUCTION
  • 82. SYSTEMIC SIGNS • FAST/ IRREGULAR PULSE • WARM MOIST SKIN • FINE TREMOR • PALMER ERYTHEMA • HAIR LOSS
  • 83. DIFFERENTIAL DIAGNOSIS
  • 84. 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.
  • 85. INVESTIGATIONS
  • 86. 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
  • 87. Axial CT scan showing enlarged extra ocular muscles in thyroid eye disease
  • 88. TREATMENT
  • 89. 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
  • 90. 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)
  • 91. 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
  • 92. 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)
  • 93. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease.
  • 94. • 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.
  • 95. 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.
  • 96. 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.
  • 97. 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.
  • 98. 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
  • 99. prevalence of patients with thyroid eye disease presenting with apparent unilateral proptosis
  • 100. • 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.
  • 101. 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
  • 102. 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 .
  • 103. 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.
  • 104. • 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: