Makindo Medical Notes

Related Subjects: |Thyrotoxicosis and Hyperthyroidism |Thyroid Storm - Thyrotoxic crisis |Graves Disease (Thyrotoxicosis) |Amiodarone and Thyroid disease |Thyroid Surgery (Thyroidectomy) |Hypothyroidism |Hashimoto's thyroiditis |DeQuervain's thyroiditis |Subacute Thyroiditis |Thyroid nodule |Congenital Hypothyroidism |Thyroid Function Tests and antibodies |Post partum thyroiditis |Sick Euthyroid Syndrome |Thyroid Exam (OSCE) |Thyroid Gland anatomy and Physiology |Thyroid Cancer

Introduction

A thyroid nodule is a discrete lesion within the thyroid gland that is radiologically distinct from the surrounding thyroid parenchyma. Thyroid nodules are common, especially in women and the elderly, and the majority are benign. However, a small percentage can be malignant, making evaluation and appropriate management essential.

Epidemiology

• Prevalence increases with age; up to 50-60% of individuals over 60 may have nodules detectable by ultrasound.
• More common in women than men, with a female-to-male ratio of approximately 4:1.
• Clinically palpable nodules are found in about 4-7% of the adult population.

Clinical Presentation

• Asymptomatic: Most thyroid nodules are asymptomatic and discovered incidentally during physical examination or imaging for unrelated reasons.
• Visible Swelling: Patients may notice a lump in the neck, which may move with swallowing.
• Compression Symptoms: Large nodules or goiters can cause difficulty swallowing (dysphagia), breathing difficulties (dyspnea), or hoarseness if there is recurrent laryngeal nerve involvement.
• Thyroid Dysfunction: Nodules may be associated with hyperthyroidism or hypothyroidism, although most patients are euthyroid.
• Pain: Sudden onset of pain may indicate hemorrhage into a cystic nodule or, rarely, malignancy.

Risk Factors for Malignancy

While most thyroid nodules are benign, certain features increase the suspicion of malignancy:

• Age: Patients under 20 or over 70 years old have a higher risk.
• Gender: Although nodules are more common in women, men have a higher risk of malignancy when nodules are present.
• Radiation Exposure: History of head and neck irradiation, especially during childhood, significantly increases risk.
• Family History: Family history of thyroid cancer or genetic syndromes like multiple endocrine neoplasia type 2 (MEN2).
• Rapid Growth: A rapidly enlarging nodule or goiter raises concern.
• Fixed Nodule: Nodules that are firm, hard, or fixed to adjacent structures.
• Hoarseness or Vocal Cord Paralysis: May indicate involvement of the recurrent laryngeal nerve by a malignant nodule.
• Cervical Lymphadenopathy: Enlarged regional lymph nodes suggest metastatic spread.
• Symptoms of Compression: Dysphagia or dyspnea due to tracheal or oesophageal compression.

Differential Diagnosis

• Benign Lesions:
  • Colloid Nodules: Hyperplastic growths within a multinodular goiter.
  • Thyroid Cysts: Fluid-filled nodules, often representing degenerative changes in a nodule.
  • Follicular Adenomas: Benign tumors derived from follicular epithelium.
  • Hashimoto's Thyroiditis: Autoimmune inflammation can produce a nodular gland.
  • Subacute Thyroiditis: Inflammatory process causing tender enlargement.
• Malignant Lesions:
  • Papillary Thyroid Carcinoma: Most common thyroid cancer (~80%).
  • Follicular Thyroid Carcinoma: Second most common; more common in iodine-deficient areas.
  • Medullary Thyroid Carcinoma: Arises from parafollicular C cells; associated with MEN2 syndromes.
  • Anaplastic Carcinoma: Rare but aggressive malignancy in older patients.
  • Primary Thyroid Lymphoma: Associated with chronic lymphocytic thyroiditis.
  • Metastatic Disease: Rarely, metastasis from other cancers can present as a thyroid nodule.
• Other Causes:
  • Iodine Deficiency: Can lead to goiter formation with nodularity.
  • Physiological Enlargement: Pregnancy can cause diffuse or nodular thyroid enlargement.

Evaluation and Investigations

A systematic approach is essential for evaluating thyroid nodules to determine the risk of malignancy and guide management.

• History and Physical Examination: Assess risk factors, symptoms, and examine the thyroid gland and cervical lymph nodes.
• Laboratory Tests:
  • Thyroid Function Tests (TFTs): Measure TSH, free T4, and free T3 levels to assess thyroid function.
  • Thyroid Autoantibodies: Anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies if autoimmune thyroiditis is suspected.
  • Calcitonin Levels: May be measured if medullary thyroid carcinoma is suspected.
• Imaging Studies:
  • Ultrasound (US) of the Neck: The imaging modality of choice for evaluating thyroid nodules.
    • Assesses size, composition (solid, cystic, or mixed), echogenicity, margins, calcifications, and vascularity.
    • Helps stratify risk using classification systems like the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS).
  • Radioisotope Thyroid Scan (Scintigraphy):
    • Uses radioactive iodine or technetium to evaluate nodule function.
    • "Hot" nodules (increased uptake) are usually benign hyperfunctioning adenomas.
    • "Cold" nodules (reduced uptake) have a higher risk of malignancy but most are benign.
    • Indicated when TSH is low to assess for hyperfunctioning nodules.
  • Computed Tomography (CT) or Magnetic Resonance Imaging (MRI):
    • Used to assess large goiters, retrosternal extension, or compressive symptoms.
    • Contrast-enhanced studies can interfere with radioactive iodine uptake; caution is advised.
• Fine-Needle Aspiration (FNA) Biopsy:
  • The gold standard for evaluating thyroid nodules.
  • Ultrasound-guided FNA increases accuracy, especially for non-palpable or small nodules.
  • Cytological evaluation is reported using the Bethesda System for Reporting Thyroid Cytopathology.
• Additional Tests:
  • Molecular Testing: May be used for indeterminate cytology to assess for genetic mutations associated with malignancy.
  • Laryngoscopy: If there is hoarseness or suspected vocal cord paralysis.

Management depends on the risk of malignancy, symptoms, and patient factors.

• Benign Nodules:
  • Observation: Most benign nodules can be monitored with periodic ultrasound examinations.
  • Suppressive Therapy: Use of levothyroxine to suppress TSH is not routinely recommended due to limited efficacy and potential adverse effects.
  • Surgical Intervention: Considered if the nodule causes compressive symptoms, cosmetic concerns, or grows significantly on serial imaging.
• Malignant or Suspicious Nodules:
  • Surgical Removal: Total or hemithyroidectomy depending on the type and extent of cancer.
  • Radioactive Iodine Therapy: Used postoperatively in certain types of thyroid cancer to ablate remnant tissue or treat metastatic disease.
  • Thyroid Hormone Suppression Therapy: High-dose levothyroxine to suppress TSH, reducing stimulation of residual cancer cells.
  • External Beam Radiation or Chemotherapy: Rarely used, reserved for advanced or refractory cases.
• Indeterminate Nodules:
  • Repeat FNA: May be performed if initial cytology is non-diagnostic.
  • Molecular Testing: To aid in risk stratification and decision-making.
  • Surgical Consideration: Diagnostic lobectomy may be recommended to obtain a definitive diagnosis.
• Autonomous (Hyperfunctioning) Nodules:
  • Antithyroid Medications: To manage hyperthyroidism symptoms.
  • Radioactive Iodine Ablation: Preferred treatment for toxic nodules causing hyperthyroidism.
  • Surgery: Considered if radioactive iodine is contraindicated or in the presence of compressive symptoms.

Follow-Up

• Regular monitoring with physical examination and ultrasound as appropriate.
• Assessment of thyroid function tests periodically.
• Long-term follow-up for patients with thyroid cancer to detect recurrence.

Conclusion

Thyroid nodules are common and often benign, but thorough evaluation is necessary to exclude malignancy. A combination of clinical assessment, imaging, and cytology guides management decisions. Most thyroid cancers have a good prognosis when detected early and treated appropriately.

References

• Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133.
• Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association guidelines for management of thyroid nodules. Endocr Pract. 2016;22(5):622-639.
• Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167-1214.
• Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009;132(5):658-665.