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Thyroid Masses: Differential Diagnosis, Clinical Presentation, and Management, Study notes of Medicine

University of Santo Tomas (UST)Medicine

An in-depth analysis of thyroid masses, discussing both benign and malignant conditions. It covers the differential diagnosis, clinical presentation, and management strategies for various thyroid masses, including multinodular goiter, solitary thyroid nodule, thyroid cysts, thyroiditis, papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma, and thyroid lymphoma. The document also discusses risk factors, diagnostic evaluation, and the bethesda system for reporting thyroid cytopathology.

Typology: Study notes

2022/2023

Available from 03/05/2024

seriousmd
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Clinical Sciences – Faculty of Medicine
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Differentials of Thyroid Masses
Introduction
The thyroid gland, a butterfly-shaped endocrine organ located in the anterior neck, plays
a critical role in metabolism, growth, and development through the production of thyroid
hormones. Thyroid masses, or nodules, are common clinical findings, with a prevalence
exceeding 50% in the general population. Fortunately, the vast majority are benign.
However, a systematic approach to evaluating thyroid masses is essential to rule out
malignancy, estimate the risk of complications, and determine appropriate
management.
Differential Diagnosis
The differential diagnosis of thyroid masses is broad and encompasses both benign and
malignant conditions:
Benign Thyroid Masses:
• Multinodular Goiter (MNG): An enlarged thyroid gland containing multiple
nodules. MNGs are often asymptomatic but can cause compressive symptoms or
cosmetic concerns in cases of significant enlargement.
• Solitary Thyroid Nodule (STN): A single, discrete nodule within the thyroid
gland, the most common presentation of thyroid disease.
• Thyroid Cysts: Fluid-filled sacs within the thyroid gland, which may be purely
cystic, complex (mixed solid and cystic), or predominantly solid with a cystic
component.
• Hashimoto's Thyroiditis (Chronic Lymphocytic Thyroiditis): The most
common form of thyroiditis, an autoimmune disorder causing inflammation of the
thyroid gland, leading to hypothyroidism. May present with diffuse thyroid
enlargement or nodularity.
• Subacute Thyroiditis (de Quervain's Thyroiditis): A self-limiting inflammatory
condition of the thyroid gland often associated with viral illness, characterized by
neck pain, fever, and transient hyperthyroidism.
Malignant Thyroid Masses:
• Papillary Thyroid Carcinoma (PTC): The most prevalent form of thyroid cancer
(approximately 80% of cases), generally slow-growing with an excellent
prognosis.
• Follicular Thyroid Carcinoma (FTC): The second most common thyroid
malignancy, slightly more aggressive than PTC.
• Medullary Thyroid Carcinoma (MTC): Arises from the parafollicular C-cells of
the thyroid, which produce calcitonin. MTC can be sporadic or familial,
associated with multiple endocrine neoplasia (MEN) syndromes.
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Differentials of Thyroid Masses

Introduction The thyroid gland, a butterfly-shaped endocrine organ located in the anterior neck, plays a critical role in metabolism, growth, and development through the production of thyroid hormones. Thyroid masses, or nodules, are common clinical findings, with a prevalence exceeding 50% in the general population. Fortunately, the vast majority are benign. However, a systematic approach to evaluating thyroid masses is essential to rule out malignancy, estimate the risk of complications, and determine appropriate management. Differential Diagnosis The differential diagnosis of thyroid masses is broad and encompasses both benign and malignant conditions: Benign Thyroid Masses:

  • Multinodular Goiter (MNG): An enlarged thyroid gland containing multiple nodules. MNGs are often asymptomatic but can cause compressive symptoms or cosmetic concerns in cases of significant enlargement.
  • Solitary Thyroid Nodule (STN): A single, discrete nodule within the thyroid gland, the most common presentation of thyroid disease.
  • Thyroid Cysts: Fluid-filled sacs within the thyroid gland, which may be purely cystic, complex (mixed solid and cystic), or predominantly solid with a cystic component.
  • Hashimoto's Thyroiditis (Chronic Lymphocytic Thyroiditis): The most common form of thyroiditis, an autoimmune disorder causing inflammation of the thyroid gland, leading to hypothyroidism. May present with diffuse thyroid enlargement or nodularity.
  • Subacute Thyroiditis (de Quervain's Thyroiditis): A self-limiting inflammatory condition of the thyroid gland often associated with viral illness, characterized by neck pain, fever, and transient hyperthyroidism. Malignant Thyroid Masses:
  • Papillary Thyroid Carcinoma (PTC): The most prevalent form of thyroid cancer (approximately 80% of cases), generally slow-growing with an excellent prognosis.
  • Follicular Thyroid Carcinoma (FTC): The second most common thyroid malignancy, slightly more aggressive than PTC.
  • Medullary Thyroid Carcinoma (MTC): Arises from the parafollicular C-cells of the thyroid, which produce calcitonin. MTC can be sporadic or familial, associated with multiple endocrine neoplasia (MEN) syndromes.
  • Anaplastic Thyroid Carcinoma (ATC): A rare but highly aggressive, undifferentiated thyroid cancer with a poor prognosis.
  • Thyroid Lymphoma: A rare primary malignancy of the thyroid gland, most often non-Hodgkin lymphoma. Clinical Presentation The clinical presentation of thyroid masses can vary, and many are asymptomatic and discovered incidentally on imaging. Potential signs and symptoms include:
  • Palpable neck mass: May be the sole presenting feature, particularly in larger nodules.
  • Compressive symptoms: Dysphagia (difficulty swallowing), hoarseness, dyspnea (difficulty breathing), globus sensation (feeling of a lump in the throat).
  • Symptoms of hyperthyroidism: Heat intolerance, palpitations, weight loss, anxiety, tremor.
  • Symptoms of hypothyroidism: Fatigue, weight gain, cold intolerance, constipation, hair loss, dry skin.
  • Rapidly enlarging thyroid nodule: Raises concern for malignancy, particularly in older patients.
  • Neck lymphadenopathy: May suggest metastatic thyroid cancer or lymphoma. Diagnostic Evaluation A thorough evaluation of thyroid masses typically involves the following steps:
  1. History and Physical Exam: A detailed history, including assessment of risk factors (family history of thyroid cancer, history of radiation exposure), and a focused neck examination are crucial initial steps.
  2. Thyroid Function Tests: Evaluation of thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels is essential to determine thyroid function (normal, hyperthyroid, hypothyroid).
  3. Thyroid Ultrasound: The primary imaging modality for evaluating thyroid nodules, characterizing their size, composition (solid, cystic, mixed), echogenicity, and vascularity. Ultrasound also guides fine-needle aspiration biopsies.
  4. Thyroid Scintigraphy (Nuclear Medicine Scan): May be used to assess nodule function (hyperfunctioning "hot" nodule, or non-functioning "cold" nodule), helping to further refine risk stratification.
  5. Fine-Needle Aspiration Biopsy (FNAB): The gold standard for diagnosing malignant thyroid nodules, obtaining cells via a thin needle for cytologic examination.
  6. Molecular Testing: May be employed in cases of indeterminate cytology to analyze for genetic mutations associated with thyroid cancer, aiding in management decisions.
  • Observation: Many benign thyroid nodules are stable and require no intervention, particularly if asymptomatic. Periodic clinical evaluation and thyroid ultrasound may be performed for monitoring.
  • Levothyroxine Suppression Therapy: May be considered in an attempt to shrink non-functioning nodules, though its efficacy remains somewhat controversial.
  • Radioiodine Ablation: May be an option for large, symptomatic goiters or hyperfunctioning nodules.
  • Percutaneous Ethanol Ablation (PEI): An alternative to surgery for predominantly cystic nodules or select solid nodules.
  • Surgery: Surgical resection (lobectomy or total thyroidectomy) may be indicated for large or compressive goiters, nodules with cosmetic concerns, or those with indeterminate or suspicious cytology. Management of Malignant Thyroid Masses
  • Surgery: Surgical thyroidectomy (lobectomy or total) is the mainstay of treatment for most thyroid cancers. The extent of surgery depends on tumor size, multifocality, and the presence of nodal metastases.
  • Radioiodine Therapy: Administered post-surgically to ablate remnant thyroid tissue in selected cases of DTC (differentiated thyroid cancer - PTC & FTC), or as adjuvant therapy for higher-risk disease.
  • External Beam Radiotherapy (EBRT): May be utilized for locally advanced or inoperable thyroid cancers, or in palliative settings.
  • Systemic Therapy: Targeted therapies (e.g., tyrosine kinase inhibitors) or chemotherapy may be considered for advanced, unresectable thyroid cancers or metastatic disease. Surveillance and Follow-Up Both benign and malignant thyroid conditions warrant ongoing monitoring, with the frequency and intensity of follow-up tailored to individual risk profiles. For malignancies, surveillance typically involves:
  • Clinical examinations: Periodic assessment for symptoms and neck palpation.
  • Thyroid function testing: Monitoring TSH and appropriate replacement with levothyroxine if necessary post-thyroidectomy.
  • Thyroglobulin (Tg) measurement: A tumor marker used in the follow-up of DTC.
  • Imaging: Neck ultrasound or other imaging modalities as indicated to detect recurrence. Conclusion Thyroid masses encompass a diverse array of pathologies. A careful clinical evaluation, appropriate imaging, and often, FNA biopsy are key to distinguishing benign from

malignant lesions. Understanding the differential diagnosis, risk factors, diagnostic workup, and management strategies for thyroid masses is fundamental for healthcare providers. References

  • American Thyroid Association. Thyroid Nodules. https://www.thyroid.org/thyroid- nodules/
  • 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, American College of Endocrinology, and Associazione Medici Endocrinologi Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules – 2016 Update. Endocrine Practice (2016) 22 (5): 622-639.
  • National Cancer Institute. Thyroid Cancer Treatment (PDQ) - Health Professional Version. https://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq