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Snapshot
  • A 27-year-old woman with vitiligo presents to her primary care physician with progressive fatigue and weight loss despite a good appetite. On exam, her blood pressure is 170/110 mmHg, pulse is 110/min, diaphoretic, displays brisk reflexes, and has bilateral exophthalmos.
Introduction
  • Clinical definition
    • autoimmune hyperthyroidism
  • Epidemiology
    • demographics
      • the most common cause of hyperthyroidism in the United States
      • female dominant
      • typically 20-40 years of age
  • Pathogenesis
    • triggered by stress
      • e.g. childbirth, infection, steroid withdrawal, and trauma to the thyroid
    • stimulating autoantibodies against the TSH receptor leading to the overproduction of thyroid hormone
      • type II hypersensitivity
    • pituitary TSH is suppressed via negative feedback from elevated thyroid hormone
  • Genetics
    • HLA-DRB1 and HLA-DQB1 
    • PTNP22
  • Associated conditions
    • polyglandular autoimmune syndrome
    • pernicious anemia
    • vitiligo
    • diabetes
Presentation
  • Symptoms
    • tachycardia and/or palpitations
      • thyroid hormone increases heart rate and contractility and decreases systemic vascular resistance
    • fatigue and muscle weakness
    • weight loss
    • hyperactivity and/or tremulousness
    • diarrhea
    • warm moist skin and sweating
    • heat intolerance
    • eye pain and/or double vision
  • Physical exam
    • hypertension and/or arrhythmias
    • enlargement ophthalmopathy (proptosis and exophthalmos)
      • the hallmark of Graves disease but not always present
    • symmetrical, non-tender thyroid enlargement
    • myxedema
      • dermal accumulation of mucopolysaccharides
      • non-pitting
    • hyperreflexia
Studies
  • Diagnostic testing
    • diagnostic approach
      • screening for patients with clinical suspicion
      • autoantibody titers are diagnostic
      • imaging to differentiate etiologies of hyperthyroidism
      • ancillary laboratory tests for associated dysregulation
    • studies
      • TSH level
        • initial test of choice
      • thyroid hormone level
        • start with T4 level (total or free)
        • if T4 level is normal, T3 level may be helpful
      • autoantibody assays
        • anti-TSH antibodies are almost always positive
        • diagnostic for Graves
      • complete blood count
        • would demonstrate associated normocytic anemia, low-normal leukocytes, and low-normal platelets
      • lipid profile
        • would demonstrate associated low total cholesterol and triglyceride  
    • imaging
      • radioactive iodine (123I) thyroid scan
        • contraindicated in pregnancy
          • defer to autoantibody assays
      • computed tomography (CT) scan or magnetic resonance image (MRI) of the orbits
        • evaluation of ophthalmopathy
    • biopsy
      • not routinely indicated but would show lymphocytic infiltrates and follicular hypertrophy
  • Diagnostic criteria
    • ↓ TSH and ↑ T4
      • if T4 is normal, then possibly ↑ T3
    • positive anti-TSH antibodies
    • radioactive iodine (123I) thyroid scan 
      • diffusely increased uptake differentiates Graves from other etiologies of hyperthyroidism 
Differential
  • Multinodular toxic goiter
    • distinguishing factors
      • patchy uptake on 123I thyroid scan
      • more common in elderly patients
  • Toxic thyroid adenoma
    • distinguishing factor
      • single nodule with uptake on 123I thyroid scan
  • Iatrogenic
    • distinguishing factors
      • excessive levothyroxine intake
      • no increase in uptake on 123I thyroid scan
Treatment
  • Medical treatment 
    • first-line
      • propranolol 
        •  indication
          • sympathetic symptoms such as palpitations, muscle weakness, and/or anxiety 
          • wean when thionamides take effect
          • not definitive treatment
          • indicated for atrial fibrillation secondary to hyperthyroidism (metoprolol) 
    • second-line
      • thionamides 
        • methimazole and propylthiouracil 
        • mechanism
          • inhibits thyroid hormone synthesis
        • indication
          • propylthiouracil during pregnancy
        • adverse effects
          • agranulocytosis
            • discontinue if this occurs
          • hepatotoxicity
        • long-term remission in a minority of patients
        • not definitive treatment
    • third-line
      • radioiodine ablation (131I)  
        • most common treatment 
        • definitive treatment 
        • mechanism
          • destruction of thyroid follicular cells 
          • release of thyroid hormone secondary to destruction may lead to a transient worsening of symptoms 
            • pretreat with glucocorticoids  
        • indication
          • failed antithyroid drugs
        • contraindication 
          • pregnancy and breastfeeding
  • Surgical treatment
    • thyroidectomy
      • indication
        • cannot tolerate medical therapy
          • pregnancy
          • allergy
        • very large goiter
  • Special considerations
    • pregnancy
      • propranolol
      • propylthiouracil
      • thyroidectomy
    • ophthalmopathy
      • steroids
      • surgical decompression
      • orbital radiation
Complications
  • Life-threatening thyroid storm with fatal arrhythmia
  • Pregnancy complications
    • anti-TSH receptor antibodies may cross placenta and lead to fetal hyperthyroidism
    • cretinism from contraindicated radioiodine ablation
  • Thyroidectomy complications
    • hypothyroidism
    • laryngeal nerve palsy
    • hypoparathyroidism and hypocalcemia ‘
 

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Questions (11)
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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(M2.EC.4728) A 26-year-old G1P0 presents to her first obstetric visit after having a positive urine pregnancy test at home. Her last menstrual period was 9 weeks ago. She has no past medical history, but her mother has rheumatoid arthritis. The patient states that for several weeks, she has felt especially warm, even when her co-workers do not, and had muscle weakness. She also complains of mood swings and fatigue. At this visit, her temperature is 99.0°F (37.2°C), blood pressure is 140/81 mmHg, pulse is 106/min, and respirations are 17/min. Physical exam is notable for 3+ deep tendon reflexes bilaterally and 4/5 strength in both hips and shoulders. Ultrasound confirms the presence of a heart beat and shows a crown rump length that is consistent with a gestational age of 9 weeks and 3 days. Which of the following is the best therapy for this patient? Review Topic

QID: 108592
1

Radioactive thyroid ablation (I-31)

5%

(3/60)

2

Methimazole

15%

(9/60)

3

Propylthiouracil

73%

(44/60)

4

Prednisone

0%

(0/60)

5

Intravenous immunoglobulin

2%

(1/60)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M2.EC.4723) A 35-year-old homeless woman presents to the emergency department complaining of a strange sensation in her chest. The patient is disheveled and dirty. The patient is an immigrant and does not speak English. On physical exam you note a sweaty and nervous woman who demonstrates a mild tremor and proptosis. His pulse is 110/minute, temperature is 99°F (37.3°C), and blood pressure is 98/60 mmHg. IV fluids are started. An EKG is performed and the findings are shown in Figure A. Initial labs are drawn and pending. A urine toxicology returns negative for testable illicit substances. Which of the following is the next best step in management? Review Topic

QID: 108521
FIGURES:
1

Vagal maneuvers

30%

(17/57)

2

Adenosine

4%

(2/57)

3

Propranolol

53%

(30/57)

4

Propylthiuracil

5%

(3/57)

5

Synchronized cardioversion

9%

(5/57)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M2.EC.4694) A 40-year-old woman with a past medical history significant for pernicious anemia and vitiligo presents to the physician with the chief complaints of heat intolerance and frequent palpitations. The patient does not take birth control and her urine pregnancy test is negative today. Physical exam reveals a patient that is hyper-reflexive with a non-tender symmetrically enlarged thyroid gland. You order thyroid function tests for workup. What thyroid function values are most expected? Review Topic

QID: 107868
1

T4 elevated, free T4 normal, T3 elevated, thyroid stimulating hormone (TSH) normal

0%

(0/2)

2

T4 elevated, free T4 elevated, T3 elevated, TSH elevated

0%

(0/2)

3

T4 elevated, free T4 elevated, T3 elevated, TSH decreased

100%

(2/2)

4

T4 decreased, free T4 decreased, T3 decreased, TSH decreased

0%

(0/2)

5

T4 normal, free T4 normal, T3 normal, TSH elevated

0%

(0/2)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M2.EC.4423) A 34-year-old woman presents to her primary care physician with insomnia. She notes that she has had difficulty calming down for the past several months. She also reports feeling warm, even when others feel cold, and that her eyes appear to bulge more than she remembered (Figure A). Her TSH is found to be 0.03 mcU/mL (nl 0.4-2.5 mcU/mL), and free T4 is 5 ng/dl (nl 0.7-1.9 ng/dl). She chooses to undergo radioiodine ablation, and returns to her physician 2 days after the procedure noting increased bulging of her eyes. Which of the following steps could have decreased the risk of this complication? Review Topic

QID: 106987
FIGURES:
1

Pretreatment with a non-steroidal anti-inflammatory drug (NSAID)

0%

(0/28)

2

Pretreatment with a beta blocker

18%

(5/28)

3

Pretreatment with furosemide

0%

(0/28)

4

Pretreatment with prednisone

75%

(21/28)

5

Post-treatment with levothyroxine immediately after ablation

4%

(1/28)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(M2.EC.75) A 66-year-old man presents to the emergency department with palpitations. He has a history of hypertension and diabetes. His temperature is 97.6°F (36.4°C), blood pressure is 154/100 mmHg, pulse is 122/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, the patient is mentating normally and is in no acute distress. An ECG is performed as seen in Figure A. Initial laboratory studies including a CBC, serum chemistries, and 2 troponins are unremarkable. What is the most appropriate next step in management? Review Topic

QID: 104081
FIGURES:
1

Amiodarone

25%

(2/8)

2

Cardioversion

38%

(3/8)

3

Digoxin

25%

(2/8)

4

Labetalol

0%

(0/8)

5

Metoprolol

12%

(1/8)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5
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