Thyroid Nodule

    Based on the AAFP article Am Fam Physician. 2003 Feb 1;67(3):559-567.

    Intro & Epidemiology

    • 4-7% of population have palpable thyroid nodules, 19-67% have incidental nodules on ultrasound
    • 5% of palpable nodules are malignant (<1% of nodules cause hypothyroidism or thyrotoxicosis)
    • Nodules <1cm are not usually palpable (unless anterior)
    • Majority are benign, the key goal is to rule out cancer.
    • Pain is uncommon (if painful likely benign)


    Review of Thyroid Symptoms

    • Hyperthyroidism:
      • wt loss (good appetite), anxiety, intolerance toheat, sweating, hair loss, muscle pains, weakness, tremor, irritibility/hyperactivity.
      • nervousness, irritability, increased perspiration, palpitations, hand tremors, anxiety, poor sleep, thinning skin, brittle hair, muscle weakness, frequent BM, wt loss, good appetite, menstruation may lighten.
    • Hypothyroidism
      • Early (cold intolerance, constipation, wt gain, bradycardia, sweating, muscle/joint pains, dry/itchy skin, thin/brittle fingernails, depression, infertility (cycles irregular), elevated lipids, hyperprolactinemia, galactorrhea.


    Risk Factors ("Red Flags")

    • Extremes of age (<20yo or >65yo)
    • Male Gender
    • Symptoms of local invasion ("dysphagia, neck pain, hoarseness)
    • History of neck radiation
    • Family history of thyroid cancer or polyposis (Gardner's Syndrome)

    Physical Exam:

    • Thyroid exam
    • Lymph nodes


    Differential Diagnosis

    • Solitary:
      • Cyst
      • Thyroid Adenoma (Benign Tumour - "Hot" or "Cold")
      • Thyroid Carcinoma
        • Papillary
        • Follicular
        • Medullary
        • Anaplastic
      • Lymphoma
      • Thyroglossal Duct Cyst
      • Reidel's Struma
    • Multiple - Multinodular Goiter



    • Macrofollicular adenoma (simple colloid) - Benign, but may share features of follicular carcinoma
    • Microfollicular adenoma (fetal) - 5% malignant
    • Colloid Nodule - most common, no increased risk of malignancy



    • Subacute thyroiditis



    • Usually presents with a solitary palpable nodule
    • Types:
      • Papillary (75%)
      • Follicular (10%)
      • Medullary (5-10%)
      • Anaplastic (5%)

    Diagnostic Algorithm

    • 1st Thing: Is TSH suppressed?

      • If Low --> Thyroid Scan and Radioactive Iodine Uptake

        If Not Low --> Thyroid Ultrasound +/- FNA

        • If FNA = Benign --> continue regular F/U
        • If FNA = Insufficient --> Repeat FNA (US guidance)
        • If FNA = Follicular neoplasm or malignant --> Call Surgeon


    • Thyroid Antibody Levels appropriate in pts with multinodular goitres or autoimmune suspected
    • Calcitonin Measurement NOT recommended (fused to follow disease activity in medullary thyroid cancer)
      • Used to follow disease activity in medullar thyroid cancer.
      • MEN2 or related disorders.
    • Serum Thyroglobulin level 
      • Primary tumor marker with well differentiated thyroid cancer who had thyroidectomy and RAI Ablation.


    Based on the American Association of Clinical Endocrinologists (taken from AAFP website)


    Diagnostic Tests



    • Ultrasound

      • ALL patients with new thyroid nodules should undergo U/S to assess:
        • Confirm the presence
        • Malignant Features
          • Hypoechoic
          • Hypervascular
          • Microcalcifications
          • Irregular Border 
          • Taller than Wide on saggital view
          • Size > 3cm
        • Benign Features:
          • Comet Tail
          • Increased peripheral nodule vascularity
          • Hyperechoic
          • Halo present
          • Pure Cyst
        • Presence of additional nodules
        • Lymphadenopathy.
    • CT/MRI not indicated, unless suspect substernal goitre or cervical adenopathy or tracheal compression.
    • Radioactive Iodine Uptake Scan (RAI scan)

      • Useful if euthyroid, but multiple nodules - to see which nodules are concerning
      • Useful if thyrotoxic (low TSH), to see if nodule is cold (risk of cancer) or hot (no risk of cancer)
    • TSH

      • Based on several studies, correlates with risk of cancer and severity.
        • If TSH is low, indicating overt or subclinical hyperthyroidism, the possibility of hyperfunctioning nodule is increased and should do RAI scan.
        • If TSH is normal or elevated, meets criteria for sampling, need FNA bx. + evaluate for hypothyroidism.
      • Based on one study (J Clin Endocrinol Metab. 2006;91(11):4295.)
        • 2.8, 3.7, 8.3, 12.3, and 29.7 percent for patients with serum TSH concentrations <0.4 mU/L, 0.4 to 0.9 mU/L, 1.0 to 1.7 mU/L, 1.8 to 5.5 mU/L, and >5.5
        • TSH Risk of Thyroid Ca
          <0.4 mU/L 2.8%
          0.4 mU/L 3.7%
          0.9 mU/L 8.3%
          1.0 mU/L 12.3%
          1.7 mU/L 29.7%
    • FNA Biopsy
      • Any solid & hypoechoic nodules >1cm should be biopsied
        • Or >2cm if mixed (cystic and solid)    
      • No biopsy necessary if:   (Consider if significant risk factors!)
        • Smaller than 1cm
        • Not growing on annual U/S exam
        • Pure Cyst
        • Hot Nodule



    • Possibilities:
    1. Benign Nodule
    2. Malignant Nodule
    3. Non-Diagnostic Sample
    4. Nodule Suspicious For Malignancy
    5. Follicular Neoplasm
    6. Follicular Lesion of Undetermined Significance
    • 5 & 6 = Increased risk --> Generally refer for surgery to excise and pathology. 



    • Call Surgery if:
      • Malignant Nodules
      • Hypoparathyroidism
      • Recurrent Laryngeal nerve paresis
      • >4cm & ass'd worrisome findings (cervical lymphadenopathy, hoarseness, external radiation, lab findings).
    • Benign Nodules
      • Monitor with periodic neck exams & ultrasound (q6-18mo)
      • Repeat FNA biopsy recommended if grown in interval (>50% by volume, or >20% in 2-dimensions, or suspicious findings)
      • If stable >18mo, can change screening for q3-5y

    Multinodular Goiter

    • In iodine-sufficient areas, has both solid and partially cystic thyroid nodules.
    • More common in older patients.
    • Over time can grow to require treatment.
    • Dx:
      • FNA needed to exclude cancer
    • Complications:
      • Can impinge on esophagus and recurrent laryngeal nerve
        • --> dyspnea, stridor, cough, fullness sensation, hoarseness.
      • Some nodules can become large enough to suppress TSH and make pt thyrotoxic.
    • Tx:
      • Thyroidectomy if causes compressive symptoms or thyrotoxic.
      • Use methimazole for thyrotoxic pts.
      • Radio-iodine 131I -> decreases size, but not first line.  (useful if thyrotoxic, doesn't reliably shrink the gland).
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