Updated: 11/27/2020

Graves Disease

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Questions
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Evidence
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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)
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(M1.EC.13.62) A 25-year-old Hispanic male presents with heat intolerance and recent weight loss. Serum analysis shows increased levels of T4 and T3, as well as the presence of thyroglobulin-stimulating immunoglobulins. The patient is found to be tachycardic and has marked edema and waxy discoloration in his legs. Which of the following would be consistent with this patient's disease? Tested Concept

QID: 100363
1

Sympathetic underactivity

0%

(0/32)

2

Anti-thyroglobin antibodies

3%

(1/32)

3

Exophthalmos

94%

(30/32)

4

Increased TSH release

3%

(1/32)

5

Multinucleate giant cells present in the thyroid

0%

(0/32)

M 2 E

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(M1.EC.12.26) A patient suffering from Graves' disease is given thiocyanate by his physician. Thiocyanate helps in the treatment of Graves' disease by: Tested Concept

QID: 100327
1

Inhibiting thyroid peroxidase

6%

(1/18)

2

Inhibiting 5'-deiodinase

28%

(5/18)

3

Inhibiting thyroid deiodinase

6%

(1/18)

4

Inhibiting beta-adrenergic receptors

6%

(1/18)

5

Inhibiting iodide follicular uptake

50%

(9/18)

M 3 E

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(M1.EC.12.109) A 25-year old Caucasian female presents with symptoms of Graves' disease. Her doctor prescribes medications and sends the patient home. After two months of therapy, the patient returns upset that her exophthalmos has not gone away. Which of the following drugs should the physician have prescribed to treat the exophthalmos? Tested Concept

QID: 100410
1

Propanolol

6%

(9/162)

2

Metropolol

0%

(0/162)

3

PTU

10%

(16/162)

4

Corticosteroids

65%

(105/162)

5

No treatment as this will resolve naturally

19%

(30/162)

M 4 C

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Evidence (8)
Topic COMMENTS (20)
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