Graves Disease

Snapshot

• A 34-year-old woman presents to the physician’s office with complaints of weight loss and sweatiness.  She states that despite a ravenous appetite, she has lost 4 pounds this past month.  In addition she states that she has been more sweaty lately, and unable to cool down in rooms that others find comfortable.  On physical exam you see an anxious and fidgety woman who has a very prominent gaze with protuberant eyes.

Introduction

• An autoimmune disease with stimulating anti-TSH receptor antibodies 
  • a type II hypersensitivity
  • anti-microsomal and anti-thyroglobulin antibodies also present (more commonly associated with Hashimoto’s thyroiditis and hypothyroidism)
  • anti-TSH antibodies also stimulate retroorbital fibroblasts → exopthalmos
• Epidemiology
  • most common cause of hyperthyroidism
  • female dominant
    • HLA-B8, -DR3 association 
  • often incited during stress
• e.g., childbirth, infection, and steroid withdrawal

Presentation

• Symptoms
  • hyperthyroidism 
• Physical exam
  • symmetrical, non-tender thyroid enlargement
  • ophthalmopathy (proptosis and exopthalmos) 
    • due to glycosaminoglycan deposition 
  • pretibial myxedema
• digital swelling

Evaluation

• Serology 
  • ↑ total serum T4
  • ↑ free T4
  • ↑ ¹²³I uptake diffusely on radioactive iodine uptake scan
  • ↓ serum TSH 
• Histology not a routine part of evaluation, but on histology may see scalloping of the colloid
• increased activity of the epithelium to produce increased thyroid hormone

Treatment

• Pharmacologic
  • β-blockers
    •  symptomatic relief via blockade of beta-1 adrenergic receptors
    • propranolol inhibits peripheral T4 to T3 conversion by deiodinase
  • thiocyanate  
    • inhibits the Na-I symporter located on the basolateral membrane of thyroid epithelial cells
      • decreased iodide uptake leads to decreased hormone synthesis
  • thionamides 
    • inhibits thyroid peroxidase
    • result in reduced hormone synthesis
  • ¹³¹I ablation
  • glucocorticoids
• treatment of exophthalmos

Prognosis, Prevention, and Complications

• Complications
  • stress-induced catecholamine surge
    • may be fatal by arrhythmia
  • pregnancy complications
    • anti-TSH receptor antibodies may cross placenta and produce hyperthryoidism in the fetus 
• may present with tachycardia, goiters, growth delays, microcephaly, or craniosynostosis

High Yield

• Presentation
  • a female patient with weight loss, tachycardia, irritability, pretibial myxedema and exopthalmos
• Pathophysiology
  • TSH stimulating antibodies stimulate TSH receptors (–>hyperthyroidism)
    • associated with other autoimmune disorders and HLA B8 and DR3
  • stimulation of thyroid gland leads to
    • increased T4 and T3
    • decreased TSH
    • diffuse increase in radioactive iodine uptake
  • exophthalmos
    • caused by lymphocytic infiltration 
    • TSH stimulating antibodies can stimulate retro-orbital fibroblasts
    • antithyroid medications will not improve/reverse
    • glucocorticoids may help decrease inflammation
• Management
  • best initial step: propranolol and propylthiouracil
    • be aware of agranulocytosis with thionamides
  • definitive management: radioactive iodine ablation (in general) or surgical removal of the thyroid in extreme cases (pregnancy)