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Thyroid Nodules                                                                                                               REF:  ACP PIER 2006

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A thyroid nodule is a discrete lesion within the thyroid gland that is palpably and/or ultrasonographically distinct from the surrounding thyroid parenchyma.

Prevalence of Thyroid Nodules:

  • Findings from palpation alone suggest that the prevalence of thyroid nodules in the general population ranges from 4% to 7%.
  • The prevalence of thyroid cancer in patients undergoing fine-needle aspiration biopsy is estimated to be about 4-5%.

Screening of Thyroid Nodule:

  1. Perform careful thyroid palpation in all patients whether or not they have specific symptoms related to the thyroid.
  2. Note that a tender thyroid nodule of acute onset suggests the presence of a hemorrhagic cyst or an area of subacute granulomatous thyroiditis.
  3. Be aware that a patient occasionally has a “pseudogoiter,” which is an enlargement of the anterior lower neck caused by fat deposition that masquerades as thyroid enlargement.

TESTS in Thyroid Nodule Evaluation:

  1. Fine-needle aspiration biopsy is the single most important procedure for differentiating benign from malignant thyroid nodules.
  2. Lab tests as Serum TSH, FT4, T3, ESR; & if indicated thyroid peroxidase antibodies (anti-TPO), thyroglobulin antibodies (anti-Tg).
  3. Thyroid Ultrasound (cyst or mass), scintigraphy ("cold" or "hot" nodule), and radioiodine scanning RAIU, together with measurement of various tumor markers, are useful adjuncts in the preoperative and postoperative management of patients with thyroid cancer.
  4. CT, MRI - Sometimes used to assess nodule size or characteristics, adenopathy, presence of calcifications, or pressure on adjacent organs

What is the appropriate evaluation of thyroid nodule?

  • A complete history and physical exam focusing on  the thyroid gland & adjacent cervical lymph nodes.
    • Pertinent history as a history of head & neck irradiation, total body irradiation family history of thyroid carcinoma in a first-degree relative, rapid growth of the nodule, hoarseness, dysphagia, neck pain or pressure, & exposure to fallout radiation from Nuclear plant; any symptoms of hyperthyroidism (e.g due to an autonomous “hot” nodule) or hypothyroidism (e.g. due to Hashimoto's thyroiditis).
    • Pertinent physical as vocal cord paralysis, ipsilateral cervical lymphadenopathy, fixation of the nodule to surrounding tissues, very firm nodule.
  • Laboratory tests
    • Serum TSH
    • Serum calcitonin for detection of C-cell hyperplasia & medullary thyroid cancer at an earlier stage.
    • Serum thyroglobulin in not routinely recommended, for it can be elevated in most thyroid diseases and & is an insensitive & nonspecific test for thyroid cancer.
    • FT4, T3, ESR; & if thyroiditis is suspected - thyroid peroxidase antibodies (anti-TPO), thyroglobulin antibodies (anti-Tg).
  • Imaging studies
    • If serum TSH is low:  Radionuclide thyroid scan 99Tc thyroid scan or 123I thyroid scan (RAIU)  (to determine "hot" , "warm, or "cold" nodule)
      "hot" functioning nodule rarely harbor malignancy.
    • If serum TSH is normal or high:  Diagnostic thyroid ultrasound to determind if there is truly a thyroid nodule that corresponds to the palpable abnormality or a thyroid cyst, and the location & the number of the "nodules".
    • CT, MRI - Sometimes used to assess nodule size or characteristics, adenopathy, presence of calcifications, or pressure on adjacent organs, or metastasis.
  • Fine Needle Aspiration Biopsy (FNAB) is the most accurate & procedure of choice for evalluating thryoid nodules,  for differentiating benign from malignant thyroid nodules.
    1. Nondiagnostic aspirates - cysic nodules that repeatedly yield nondiagnostic aspirates need close observation or surgical excisioin; surgery should be more strongly considered if the cytologically nondiagnostic nodule is solid.
    2. Aspirates suggesting malignancy - surgery is recommended
    3. Indeterminate cytology  (suspicious, follilcular lesion, or follilcular neoplasm) -  a radioiodine thyroid scan should be considered, if not already done.  If a concordant autonomously functioning nodule is not seen,  lobectomy or total thyroidectomy should be considered.
      If the reading is "suspicious for papillary carcinoima or Hurthle cell neoplasm", lobectomy or total thyroidectomy is recommended. (a radionuclide scan is not needed)
    4. Benign cytology - further immediate diagnostic studies or Rx are not routinely required.   Routine thyroid hormone suppression therapy to decrease nodule size is not recommended.

Thyroid Fine-Needle-Aspiration Biopsy Results

  • Diagnostic (satisfactory)
    1. Benign (negative):  Colloid nodule, Hashimoto thyroiditis, subacute (granulomatous) thyroiditis, cyst
    2. Suspicious ((indeterminate):  Follicular neoplasm, Hürthle cell neoplasm, other findings that suggest (but are not diagnostic of) malignancy
    3. Malignant (positive):  Papillary carcinoma, medullary carcinoma, anaplastic carcinoma, metastatic carcinoma
  • Nondiagnostic (unsatisfactory):  Foam cells only, cyst fluid only, too few follicular cells, excessive air drying, too much blood

* Multi-nodular goiter:  patients with multiple thyroid nodules have the same risk of malignancy as those with solitary nodule.  A diagnostic ultrasound should be performed to delineate the nodules.  In the presence of two or more thyroid nodules larger than 1-1.5 cm, those with a suspicious sonographic appearance should be aspirated preferentially.

* Consider early referral to a endocrinologist specialist for FNAB of the thyroid before performing any diagnostic imaging.

  1. Obtain thyroid FNAB through consultation with an endocrinologist, pathologist, or surgeon.
  2. Consult a radiologist or endocrinologist for guidance on ultrasonography or ultrasound-directed FNAB.

Consider other imaging studies when obstructive symptoms are suspected.

  1. Consider CT or MRI to evaluate multinodular goiters causing pressure symptoms, but do not perform them routinely in patients with thyroid nodules.
  2. Consider barium swallow if there is dysphagia to exclude other causes.
  3. Consider pulmonary function testing with flow-volume loops to assess upper airway function.


 Screening  |  Diff-Dx  |  RX      
Differential Diagnosis of Thyroid Nodules  
  1. Thyroid carcinoma
  2. Thyroid lymphoma
    Enlarging, firm neck mass; often bilateral Classically seen in older women with a history of Hashimoto's thyroiditis
  3. Multinodular goiter
  4. Thyroid cyst or Thyroid adenoma
  5. Thyroiditis  nodule  
  6. Subacute thyroiditis
    Firm or hard, tender thyroid; may be unilateral Usually seen in association with thyroidal tenderness, systemic symptoms of fever and malaise; characterized by elevated sedimentation rate and very low radioiodine uptake
  7. Thyroglossal duct cyst
    Midline cystic mass at level of hyoid bone May become infected; rarely malignant
  8. Pyramidal lobe of hyoid
    An isthmic projection of thyroglossal duct May be palpable in autoimmune thyroid disease
  9. Delphian nodes
    Lymph nodes in midline above the thyroid May be involved and enlarge in thyroid cancer
  10. Dermoid cyst
    Soft mass in the suprasternal notch
  11. Innominate artery
    Pulsatile mass Seen in elderly patients; not a sign of aneurysmal dilatation
  12. Cervical lymphadenopathy
    Firm, matted, fixed anterior cervical nodes May be associated with malignancy, including thyroid cancer
  13. Branchial cyst
    Soft, resilient mass interior to upper one third of eidomastoid Usually seen in adults; cyst fluid contains cholesterol crystals
  14. Carotid body tumor
    Cystic or hard mass at carotid bifurcation Use caution; may produce bradycardia or dizziness with pressure on the tumor

Thyroid Cancer

  1. Papillary carcinoma
    - most common variety, 60-70% of thyroid tumors. May be associated with radiation exposure. Tumor contains psammoma bodies.
    - Metastasizes by lymphatic route (30% at time of diagnosis).
  2. Follicular carcinoma
    - 10-20% of thyroid tumors. The incidence has been decreasing since the addition of dietary iodine. It occurs usually in females over 40 years of age.
    - Metastasizes by the hematogenous route.
  3. Hurthle cell carcinoma
    - usually in patients over 60 years of age. Radioresistant. Composed of distinct large eosinophilic cells with abundant cytoplasmic mitochondria.
  4. Medullary carcinoma
    - arises from parafollicular cells, C-cells. 2-5% of all thyroid tumors. 25-35% are associated with multiple endocrine neoplasia (MEN) syndromes which can be familial or sporadic. Calcitonin is a chemical marker.
    is found in about 5% of patients with thyroid malignancy.
    About three fourths of patients with medullary cancer have the "sporadic" form, whereas the other 25% have a hereditary form that may be part of the multiple endocrine neoplasia type 2 (MEN-2) syndromes.
    In medullary thyroid cancer, nodal metastatic involvement is associated with increased risks for both recurrence and death .
  5. Anaplastic carcinoma
    - 3-5% of thyroid tumors, usually in patients over 60 years of age
    -Anaplastic cancer, which is the most aggressive known solid tumor of any organ, has a rapid and relentless course and can cause death within months of diagnosis.
  6. Other - lymphoma, sarcoma, or metastatic (renal, breast or lung)


 Screening  |  Diff-Dx  |  RX      
Management of Thyroid Nodule  

Some of the Indications for Thyroid Nodule Surgery:

  1. A malignant or suspicious thyroid nodule on FNAB.
  2. Consider primary lobectomy for benign nodules.
  3. COnsider surgery when there is continued nodule growth, despite benign FNAB results
  4. Consider near-total thyroidectomy for papillary or follicular carcinoma.
  5. Consider bilateral subtotal thyroidectomy for multinodular goiters.
  6. Consider surgery in patients who have benign cytology on FNAB but who have compressive symptoms, fears about the possibility of cancer, and/or cosmetic concerns.

Consider surgical treatment for certain benign nodules.

  • Consider surgical treatment for solitary “benign” nodules when:
    1. There is continued nodule growth despite benign FNAB results
    2. Cytology is benign but the clinical impression is suspicious (i.e., there is growth, the patient is aged <20, and there is a history of radiation exposure)
    3. There are compressive symptoms (e.g., dysphagia, shortness of breath, hoarseness) from a large nodule or multinodular goiter
    4. Solid or cystic lesions remain nondiagnostic on repeated biopsies
    5. There are cosmetic considerations
  • For single benign nodules, consider primary lobectomy with or without isthmectomy.
  • If a malignancy is discovered intraoperatively or on final pathology, consider completion thyroidectomy.

Recognize that T4-suppression therapy remains controversial and is not recommended.

  • Recognize that T4 therapy is not recommended for most patients with thyroid nodules.
  • Note that T4 therapy might be considered in a patient with a benign nodule cytology whose nodule is enlarging.
  • To avoid untoward effects of excessive T4, ensure that the target serum TSH level is not <0.2 to 0.3 mIU/L.
  • In postmenopausal women, be sure that T4-suppressive therapy is accompanied by calcium supplementation and possibly even estrogen therapy, particularly if BMD is >2 SD below normal.
  • T4 therapy may be effective in decreasing the size of benign thyroid nodules that occur in patients with a history of external-beam radiotherapy.
  • TSH may not be the dominant growth factor in nodule growth; thus, suppressing it with thyroid hormone may not be effective in shrinking thyroid nodules.
    Early reports that suggested the effectiveness of T4-suppressive therapy were generally uncontrolled studies.
    Overall, <20% of thyroid nodules seem to respond to T4-suppressive therapy.
    TSH suppression in elderly, otherwise healthy individuals increases the risk of atrial fibrillation threefold (106), increases bone loss (103; 107), and possibly increases fracture rates in postmenopausal women


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REF: Thyroid Nodule Guideline 2006 (American Thyroid Association)