Thyroid Disease

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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. Pathophysiology of Thyroid Eye Disease

⭐ 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.

Clinical signs of Thyroid Eye Disease

⭐ 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). Orbital CT: Fusiform extraocular muscle enlargement in TED

⭐ 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_._

Practice Questions: Thyroid Disease

Test your understanding with these related questions

Which of the following conditions is the most common complication of radioiodine treatment for Graves' disease?

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Flashcards: Thyroid Disease

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Non-surgical management for thyroid ophthalmopathy: Systemic _____, Radiotherapy and Guanethidine 5% eye drops

TAP TO REVEAL ANSWER

Non-surgical management for thyroid ophthalmopathy: Systemic _____, Radiotherapy and Guanethidine 5% eye drops

steroids

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