Thyroid Disorders

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The Thyroid: Functional vs Anatomic Abnormalities--

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*Functional abnormalities
-Hyperfunction
-Hypofunction

*Anatomic abnormalities
-Goiter
-Nodules (single or multiple, benign or malignant)

*Thyroid disease often presents with both types of abnormalities – sometimes the abnormalities are related, sometimes not

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daaaaaaaaaaaaamnnnnn!

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Goiter:

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*Enlargement of the thyroid gland.

*Goiters occur for a variety of reasons and can be associated with normal thyroid function, hypothyroidism, or hyperthyroidism

*Goiter is not generally associated with cancer in the absence of nodules

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Thyroid Nodule:

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A thyroid nodule is a localized portion of the gland that has a different contour or consistency than the normal gland -- or on imaging, has a different “texture.”

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Symptoms of Thyroid Nodules:

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*Physical examination and symptoms will depend on size and location

*Small nodules- usually asymptomatic

*Large nodules:
-Often asymptomatic
-Cosmetic concern
-Hoarseness - Laryngeal n. compression
-Stridor, cough, dysphagia, pressure sensation
-Substernal or posterior extension (?Pemberton Sign)
-Tracheal deviation or compression

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*Palpable and Visible Thyroid Nodule

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Thyroid Nodule Displacing Trachea

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Goiter Causing Tracheal Compression

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Pemberton Sign

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Discuss the Prevalence of Thyroid Nodules:

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95% nodules are benign

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Pathologic Classification of Thyroid Nodules:

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Benign Adenoma: Etiology--

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*Environmental factors: iodine intake, natural goitrogens, tobacco

*Genetic mutations
-Na-I Symporter: hypofunctional
-TSH receptor: hyperfunctional

*Age, gender, other

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Thyroid adenoma: Pathological Characteristics--

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*Discrete capsule
*Orderly architecture
*Few mitoses
*No lymphatic or arterial invasion

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Thyroid adenoma
*Discrete capsule
*Orderly architecture
*Few mitoses
*No lymphatic or arterial invasion

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Benign Thyroid Nodule: Treatment Options--

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*No treatment; continued monitoring

*Surgery

*131I Radioiodine--Mainly for toxic nodules

*Percutaneous ethanol injection--For cystic nodules

*Radiofrequency ablation (RFA) and laser treatment-- (Experimental procedures)

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Thyroid Nodule: Diagnostic Testing:

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*TSH

*Imaging:
-Neck sonogram
-Neck CT or MRI
-Radioisotope scan

*FNA

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Thyroid Ultrasound:

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*Sends and receives sound waves

*Image is created based on the density of the examined tissue

*Thyroid and adjacent neck anatomy is visualized in detail

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thyroid ultrasound

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Thyroid nodule ultrasound Complex nodule

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Thyroid nodule ultrasound Simple cyst

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Thyroid Ultrasound: Features Associated with Increased Cancer Risk--

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*Microcalcifications

*Hypoechoic, solid lesion

*Infiltrative margins

*Increased vascularity

*Nodules < 10 mm diameter are not generally biopsied unless patient has a high-risk history for thyroid cancer

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ultrasound--Thyroid cancer-microcalcifications

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ultrasound--Thyroid cancer-chaotic vascularity

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*Radioisotope Scan
L: Multiple cold nodules
R: Hot nodule!!!!!

*A scan is generally performed only in those patients with low TSH in order to identify toxic nodules, which don’t warrant FNA

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Thyroid Nodule: Role of CT/ MRI:

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*To better characterize the relationship of thyroid gland to surrounding structures:
-Tracheal deviation or compression
-Mediastinal extension
-Deep neck or mediastinal lymph nodes

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Thyroid FNA

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Thyroid Nodule: Evaluation Algorithm:

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Recommendations for interpreting FNA results:

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Thyroid Cancer: Molecular Biology--

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How are thyroid cancer rates in the US changing?

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Thyroid Cancer- prevalence and general info:

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*Prevalence: 5-10% of all thyroid nodules

*Possible 5% prevalence in general population when counting clinically insignificant micro-cancers

*Well-differentiated thyroid cancer is one of the most curable malignancies

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How is survival from thyroid CA?

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Clinical Features Indicating Higher Risk for Nodule Malignancy:

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*Age-- <20 and >70

*Gender--Male

*Fam Hx--Thyroid cancer, MEN2, Cowden Syndrome, Gardner Syndrome

*H/O head or neck irradiation during childhood or adolescence

*Prior h/o thyroid cancer

*Abnormal lymph nodes

*High calcitonin level

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Discuss the role of Ionizing Radiation in thyroid CA:

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*Exposure before age 21 increases the risk of papillary thyroid cancer

*Risk increases with lower age and increasing radiation dose, 10cGy to 1500cGy

*Risk of cancer can be increased >50x

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Thyroid Cancer: Classification--

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*Epithelial
-Follicular cell: Papillary carcinoma, Follicular carcinoma, Hurtle cell carcinoma
-Undifferentiated: Anaplastic
-C-cell: Medullary

*Nonepithelial
Secondary tumors, lymphoma, sarcoma

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Papillary Thyroid Cancer:

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*90% of all thyroid cancers
-Follicular cells arranged in papillary projections
-Large pale irregular nuclei
-40% contain Psammoma bodies

*Multifocal in ~40%

*Excellent prognosis for ~90% of patients

*Tends to metastasize locally (~20%)

*Distant metastases in <5%

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Follicular Thyroid Cancer:

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*Cytological features:
-Cuboidal cells with large nuclei
-Usually unifocal
-Cells similar to follicular adenoma
-Diagnosis based on invasion of blood vessels and/or tumor capsule

*More aggressive then papillary thyroid cancer

*Spreads hematogenously to lungs & bones

*Local lymph node metastases are rare

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Medullary Thyroid Cancer:

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*Arises from parafollicular C cells
-Calcitonin, Carcinoembryonic antigen

*Sheets of cells separated by pink staining ‘amyloid like’ substance

*More aggressive then papillary and follicular thyroid cancer

*Metastases to both nodes and distant organs

*RET proto-oncogene mutation

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Less common Cancers Involving the Thyroid:

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*Anaplastic cancer
-Very aggressive with poor prognosis
-Typically older patients with long-standing goiter or differentiated thyroid cancer
-Invasive neck involvement and distant metastases are common

*Lymphoma
-30-80% have Hashimoto thyroiditis
-Rapid enlargement of gland or nodules is typical, often causing neck symptoms

*Secondary cancers
-Melanoma, breast, lungs, colon, lymphoma

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Mortality rates for thyroid carcinoma:

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Treatment of Follicular and Papillary Thyroid Cancer:

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*Surgery
-Near-total thyroidectomy
-Partial thyroidectomy

*Lymph node dissection

*Radioiodine ablation/treatment

*Levothyroxine (Low TSH target)

*External beam radiation

*Tyrosine kinase inhibitors

*Chemotherapy: no benefit

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Radioactive Iodine Treatment:

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*Adjunctive therapy for higher stage tumors

*Requires high TSH level and low dietary iodine intake to achieve therapeutic dose in cancer cells
-Hypothyroidism (stop L-T4 or L-T3), or Recombinant TSH

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Other Thyroid Cancers: Treatment--

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*Medullary
-Surgery for localized disease
-External beam radiation

*Anaplastic
-No effective treatment
-Debulking surgery for local disease

*Lymphoma: Chemotherapy