Thyroid Disease

Pathophysiology of TED - Immune Eye Attack

• Autoimmune, strong association with Graves' disease.
• Target: TSH receptor (TSH-R) on orbital fibroblasts.
• Immune Cells:
  • T-cell infiltration (Th1, Th2, Th17).
  • B-cells → TSH-R autoantibodies (TRAbs).
• Mediators:
  • Pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IFN-γ) drive inflammation.
• Orbital Fibroblast Response:
  • Adipogenesis → ↑ orbital fat.
  • ↑ Hyaluronan (GAG) synthesis.
    • Hyaluronan → edema, muscle swelling.
• Outcome: Extraocular muscle (EOM) & orbital fat expansion → proptosis, compressive optic neuropathy.

⭐ TSH-R autoantibodies (TRAbs), especially Thyroid Stimulating Immunoglobulins (TSIs), are key initiators of the autoimmune attack on orbital tissues in TED.

Clinical Spectrum of TED - Orbit's Outcry

Thyroid Eye Disease (TED) presents with a wide range of orbital signs and symptoms, often asymmetric. Severity is graded using the 📌 NOSPECS classification:

• No signs or symptoms.
• Only signs (no symptoms):
  • Upper lid retraction (Dalrymple's sign): stare appearance.
  • Lid lag on downgaze (von Graefe's sign).
• Soft tissue involvement:
  • Periorbital edema, erythema.
  • Chemosis, conjunctival injection (especially over rectus muscle insertions).
• Proptosis:
  • Axial, usually bilateral; can be unilateral.
  • Measured by exophthalmometry; > 21 mm or > 2 mm asymmetry.
• Extraocular muscle (EOM) involvement:
  • Restrictive myopathy (fibrosis) → diplopia, ophthalmoplegia.
  • Order of involvement: Inferior rectus (most common), Medial, Superior, Lateral (📌 IMSL).
• Corneal involvement:
  • Exposure keratopathy (due to proptosis, lid retraction).
  • Superior limbic keratoconjunctivitis.
• Sight loss (Optic Neuropathy):
  • Optic nerve compression at orbital apex by enlarged EOMs.
  • ↓ Visual acuity, dyschromatopsia, visual field defects, RAPD.

⭐ TED is the most common cause of both unilateral and bilateral proptosis in adults.

Diagnosing Thyroid Eye Disease - Eye Spy Thyroid

• Clinical Clues: History (thyroid disease, smoking), proptosis, lid retraction/lag, diplopia, optic neuropathy.
• Activity Assessment: Clinical Activity Score (CAS). Score ≥ 3/7 (7 inflammation signs: pain, redness, swelling) indicates active TED.
• Severity Grading: EUGOGO classification (Mild, Moderate-to-Severe, Sight-threatening).
• Investigations:
  • Labs: TFTs (TSH, FT3, FT4), TSH Receptor Antibodies (TRAb).
  • Imaging (CT/MRI Orbit): EOM belly enlargement (tendon sparing), apical crowding. 📌 Most common: Inferior Rectus (I'M SLOW).

⭐ TSH Receptor Antibody (TRAb) levels often correlate with TED activity and severity.

Managing Thyroid Eye Disease - TED Taming Tactics

• Goals: Euthyroidism, symptom relief, vision preservation, QoL improvement.
• Crucial: Smoking cessation. Maintain euthyroidism.
• Supportive: Lubricants, cool compresses. Selenium (200 mcg/day) for mild active TED.
• IV Methylprednisolone (IVMP): First-line for moderate-severe & sight-threatening TED.
  • Mod-Sev: Pulses (e.g., 0.5g wkly x6, then 0.25g wkly x6; total 4.5-8g).
  • Sight-threatening: High-dose (e.g., 0.5-1g daily x3 days).
• Other Immunomodulators:
  • Teprotumumab (anti-IGF-1R): Reduces proptosis, diplopia.
  • Rituximab (anti-CD20), Mycophenolate: Steroid-sparing/resistant cases.
  • Orbital Radiotherapy (ORT): Adjunct for diplopia/inflammation.
• Surgery (Inactive Phase): Sequence 📌 OML: Orbit (decompression) → Muscles (strabismus) → Lids (retraction).

⭐ Teprotumumab, an IGF-1R inhibitor, is a significant advancement for active moderate-to-severe TED, directly targeting proptosis and diplopia with notable efficacy.

High‑Yield Points - ⚡ Biggest Takeaways

• TED is the most common cause of adult proptosis (unilateral/bilateral).
• Key signs include lid retraction (Dalrymple's) & lid lag (von Graefe's).
• NO SPECS classifies severity; optic neuropathy (S) is most vision-threatening.
• Inferior rectus is most commonly involved (IMSLO), causing vertical diplopia & restricted upgaze.
• Exophthalmometry: >21 mm or >2 mm asymmetry is significant for proptosis.
• Management: Active inflammation treated with IV steroids (first-line); decompression for optic neuropathy/severe proptosis_._