Updated: 2/25/2020

Thyroid Cancer

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Review Topic
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Snapshot
  • A 32-year-old woman complains of fatigue and difficulty swallowing for the past month. The patient has also noted that her voice has been sounding different for the past 2 weeks. On physical exam there is a palpable, nontender nodule in the front of her neck that moves with swallowing. There is no cervical lymphadenopathy. Ultrasound of the neck shows a 1.9 cm nodule with microcalcifications. 
Introduction
  • Overview
    • primary malignancy of thyroid gland
    • secondary metasteses can occur from other cancers
      • breast, colon, renal, and melanoma
  • Epidemiology
    • incidence
      • increasing in past 15 years
      • papillary thyroid cancer (most common) has incidence of 15 per 100,000
    • demographics
      • papillary more common in women
      • anaplastic more common in elderly
    • risk factors
      • < 30 or > 70 years of age
      • history of radiation to head/neck
      • family history of
        • medullary thyroid cancer
        • multiple endocrine neoplasia (MEN) syndrome type 2
        • Cowden syndrome
        • familial adenomatous polyposis
  • Prognosis
    • papillary has very good prognosis
    • anaplastic has very poor prognosis
Classification
  • Papillary 
    • overview
      • 85% of all thyroid cancers 
      • female dominance
      • often multifocal
      • risk factors include radiation exposure to the head and neck
      • spreads via lymphatics
      • very good prognosis
    • histology
      • psammoma bodies (calcifications)  
        • also seen in ovarian papillary serous cystadenocarcinoma and meningiomas
      • ground glass/empty nuclei  
        • nuclear grooves
        • known as "Orphan Annie" eyes
      • cells organized into papillary "fingers" 
  • Follicular carcinoma
    • overview
      • usually unifocal
      • small number evolved from a benign follicular adenoma
        • requires surgical excision to differentiate between adenoma and carcinoma
          • follicular carcinoma shows invasion into capsule and vessels 
      • spreads hematogenously
        • lungs most common location of metastasis
      • good prognosis
    • histology
      • preservation of normal thyroid follicular architecture but with proliferation
        • uniform follicles
  • Medullary
    • overview
      • derived from calcitonin-synthesizing C cells
        • may present with hypocalcemia
        • may produce ACTH
      • 10% of cases associated with MEN syndrome type 2a or 2b 
        • associated with a RET mutation
      • typically unifocal thyroid nodule
      • patients have elevated serum calcitonin (tumor marker)
      • risk factors
        • previous radiation to neck
        • family history
    • histology 
      • amyloid (consisting of calcitonin) 
  • Anaplastic
    • overview
      • more common in elderly
      • can be superimposed on multinodular goiter or follicular cancer
      • very poor prognosis
Presentation
  • Symptoms
    • dysphagia and hoarseness
      • can be due to direct compression by mass
      • can indicate tumor invasion/nerve involvement
  • Physical exam
    • neck mass or palpable thyroid nodule
    • +/- cervical lymphadenopathy
      • suggests metastasis
Imaging
  • Thyroid scintigraphy (radioactive iodine uptake test)
    • indications
      • patients with decreased thyroid stimulating hormone (TSH) levels
    • findings
      • "hot" nodule 
        • increased uptake of iodine compared to surrounding thyroid tissue
        • suggests autonomously functioning thyroid
          • typically benign
          • no fine needle aspiration (FNA) required 
      • "cold" nodule
        • less uptake of iodine compared to surrounding thyroid tissue
        • concern for malignancy
        • perform FNA
  • Ultrasonography
    • indications
      • all patients with thyroid nodule
    • findings
      • hypoechoic nodule > 1 cm more likely to be malignant
      • high suspicion of malignancy if
        • hypoechoic nodule > 1 cm and has ≥ 1 suspicious features such as
          • irregular margins
          • microcalcifications 
          • rim calcifications
          • extrathyroidal extension
      • intermediate suspicion of malignancy if
        • hypoechoic nodule > 1 cm with smooth margins
Studies
  • TSH levels
    • decreased TSH more concerning for malignancy
      • follow up with thyroid scintigraphy (radioactive iodine uptake test)
    • normal/elevated TSH less concerning for malignancy
      • follow up with ultrasound
  • Serum calcitonin
    • tumor marker for medullary thyroid cancer
  • Fine needle aspiration (FNA)
    • indications
      • all "cold" nodules on radioactive iodine uptake scan
      • nodules that meet high or intermediate suspicion criteria based on ultrasound
      • nodules that are low suspicion on ultrasound but have all of the following properties
        • isoechoic, hyperechoic solid nodule, or partially cystic nodule
        • has eccentric solid areas
        • size > 1.5 cm
Differential
  • Benign thyroid nodule
    • key distinguishing factors
      • more likely to be tender
      • associated hypo- or hyperthyroidism
      • typically "hot" on radioactive iodine uptake test
Treatment
  • Medical
    • iodine radiotherapy
      • indications
        • papillary thyroid cancer
        • following surgical management in high-risk and some intermediate-risk patients
    • thyroid hormone supplementation
      • indications
        • almost all patients following initial medical/surgical management
        • prevents hypothyroidism
        • minimizes potential TSH stimulation of tumor growth
      • modalities
        • daily oral levothyroxine
  • Surgical
    • thyroidectomy
      • indications
        • FNA findings that either confirm malignancy or are suspicious for malignancy
      • risk of damage to recurrent laryngeal nerve during surgery
        • persistent hoarseness
Complications
  • Metastasis to other organs
  • Death 
 

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Questions (5)
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.ON.17.4754) A 43-year-old female presents to her primary care physician complaining of a gradually enlarging neck mass. She reports that she first developed a firm nodular midline mass on the anterior aspect of her neck two months ago. She is otherwise healthy and takes no medications. A fine-needle aspiration is performed and a histological sample of the specimen is shown. Which of the following is the most likely diagnosis? Review Topic | Tested Concept

QID: 108711
FIGURES:
1

Medullary thyroid carcinoma

20%

(65/318)

2

Follicular thyroid carcinoma

21%

(68/318)

3

Papillary thyroid carcinoma

50%

(158/318)

4

B-cell lymphoma

2%

(7/318)

5

Anaplastic thyroid carcinoma

3%

(10/318)

L 2 C

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(M1.ON.14.27) A 27-year-old female presents to her physician with a palpable thyroid nodule. Iodine uptake testing shows that the nodule has decreased iodine uptake compared with the rest of the thyroid gland. A fine-needle aspiration is performed and the physician calls telling the patient that she has a neoplasm of the thyroid. Which of the following diagnoses is the most likely? Review Topic | Tested Concept

QID: 104667
1

Papillary carcinoma

37%

(13/35)

2

Medullary carcinoma

20%

(7/35)

3

Follicular carcinoma

34%

(12/35)

4

Anaplastic carcinoma

6%

(2/35)

5

Hurthle cell carcinoma

3%

(1/35)

L 2 D

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