Updated: 12/28/2018

Graves Disease

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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 
Treatment
  • Pharmacologic
    • β-blockers
    • thiocyanate
      • inhibits the Na-I symporter located on the basolateral membrane of thyroid epithelial cells
        • decreased iodide uptake leads to decreased hormone synthesis
    • thionamides
      • 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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Questions (8)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.EC.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? Review Topic

QID: 100410
1

Propanolol

6%

(8/140)

2

Metropolol

0%

(0/140)

3

PTU

9%

(12/140)

4

Corticosteroids

66%

(92/140)

5

No treatment as this will resolve naturally

19%

(26/140)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(M1.EC.26) A patient suffering from Graves' disease is given thiocyanate by his physician. Thiocyanate helps in the treatment of Graves' disease by: Review Topic

QID: 100327
1

Inhibiting thyroid peroxidase

0%

(0/5)

2

Inhibiting 5'-iodinase

60%

(3/5)

3

Inhibiting thyroid deiodinase

20%

(1/5)

4

Inhibiting beta-adrenergic receptors

0%

(0/5)

5

Inhibiting iodide follicular uptake

0%

(0/5)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(M1.EC.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? Review Topic

QID: 100363
1

Sympathetic underactivity

0%

(0/15)

2

Anti-thryroglobin antibodies

7%

(1/15)

3

Exophthalmos

87%

(13/15)

4

Increased TSH release

7%

(1/15)

5

Multinucleate giant cells present in the thyroid

0%

(0/15)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3
Topic COMMENTS (17)
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