Thyroid nodule resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Thyroid nodule Resident Survival Guide Microchapters
Overview
Classification
Causes
FIRE
Diagnosis
Treatment
Do's
Don'ts

Overview

Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. The American Thyroid Association has published guidelines for the management of thyroid nodules, which were updated in 2015.

Classification

The various classification systems for thyroid nodules can be summarized as follows:

Causes

Life-threatening causes

The most important genes which can lead to thyroid cancer include:

• N&H ras
• RET
• Gsp
• C-MET (α and β subunit)
• TRK
• EGF / EGF-R
• P53

Causes of malignant nodule mutations:

• Childhood radioiodine exposure
• Familial history

Common causes

The most important causes of thyroid nodule development include:

• Causes of benign thyroid nodule:
  • Multinodular (sporadic) goiter ("colloid adenoma")
  • Hashimoto's (chronic lymphocytic) thyroiditis
  • Cysts (colloid, simple, or hemorrhagic)
  • Follicular adenomas
  • Macrofollicular adenomas
  • Microfollicular or cellular adenomas
  • Hürthle cell (oxyphil cell) adenomas
  • Macro- or microfollicular patterns

A Complete Diagnostic Approach and Management

Abbreviations: TSH: Thyroid stimulating hormone, FNA: Fine needle aspiration, FLUS: Follicular lesion of undetermined significance, AUS: Atypia of undetermined significance.

Thyroid nodule found clinically or incidentally                                                                                                                               TSH                                                                                                                                                                                                                                           Normal or elevated                                   Subnormal                                                                                                                                     Radionuclide thyroid scan                                                                                                                                                                   Nodule not up taking the radionuclide Cold nodule Nodule is non-functional               Nodule up taking the radionuclide Hot nodule Nodule is functional                                                                                                                                         Ultrasound evaluation               Check thyroid hormones Free T4 and T3 check                                                                                                                                                                                                                                                                         Meets the criteria           Doesn't meet criteria       Normal Subclinical hypothyroidism   Elevated Thyroid adenoma Hyperthyroidism                                                                                                                                                         Monitoring           Treat hyperthyroidism                                                         Cystic nodule   Spongiform nodule         Solid nodule                                                                                                                                     Without malignant features       Hyperechoic or isoechoic or partially cystic nodule with eccentric solid areas   Hypoechoic solid nodule with smooth margins WITHOUT the following features: Microcalcifications Extrathyroidal extension Taller than wider shape   Hypoechoic solid nodule or solid hypoechoic component of a partially cystic nodule WITH one or more of the following features: Irregular margins Microcalcifications Taller than wide shape Rim calcifications with small extrusive soft tissue component Evidence of extrathyroidal extension                                                                                                                 Very low suspicion of malignncy     Low suspicion for malignancy   Intermediate suspicion of malignancy   High suspicion of malignancy                                                                                                         Estimated risk of malignancy <3%     Estimated risk of malignancy 5 to 10%   Estimated risk of malignancy 10 to 20%   Estimated risk of malignancy >70 to 90%                                                                                                                             FNA if nodule is larger that 2cm   FNA if nodule is larger that 1.5cm       FNA if nodule is larger that 1cm                                                                                                                                                                                                                               FNA result                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Follicular neoplasm               FLUS     AUS     Benign     Suspicious for malignancy     Papillary thyroid carcinoma   Nondiagnostic                                                                                                                                                                   Repeat Ultrasound every 1-2 year If growth more>20% or suspicious ultrasound results, consider FNA again                           Repeat FNA with ultrasound guidance                                                                       Repeat FNA in 2-3 months                                 Total thyroidectomy                                                                                                                                                                     AUS FLUS               Benign                                                                                                                                                                                                                                                                                                                                                                                       Cold, non-functional nodule     Hot, functional, benign nodule                                                                                                                                                                                               Thyroid lobectomy considering ultrasound results AND Molecular diagnostic testing *Gene expression classifier * Mutational analysis                                                                                                                                                                                                                                                                                             Suspicious to malignancy               Benign                                                                                                                                                                                               Lobectomy OR Total thyroidectomy based on the ultrasound evaluation

Do's

Thyroglobulin level monitoring

• Periodic serum Tg measurements on thyroid hormone therapy should be considered during follow-up of patients with DTC who have undergone less than total thyroidectomy and in patients who have had a total thyroidectomy but not RAI ablation.

Cervical ultrasound

• Following surgery, cervical US to evaluate the thyroid bed and central and lateral cervical nodal compartments should be performed at 6–12 months and then periodically, depending on the patient's risk for recurrent disease and Tg status.

18FDG-PET scanning

• 18FDG-PET scanning should be considered in high-risk DTC patients with elevated serum Tg (generally >10 ng/mL) with negative RAI imaging

CT scans

• CT imaging of the chest without IV contrast (imaging pulmonary parenchyma) or with IV contrast (to include the mediastinum) should be considered in high risk DTC patients with elevated serum Tg (generally >10 ng/mL) or rising Tg antibodies with or without negative RAI imaging.

TSH range

• In patients with a structural incomplete response to therapy, the serum TSH should be maintained below 0.1 mU/L indefinitely in the absence of specific contraindications.
• In patients with an excellent (clinically and biochemically free of disease) or indeterminate response to therapy, especially those at low risk for recurrence, the serum TSH may be kept within the low reference range (0.5–2 mU/L).

Surgery for nodal disease

• Surgery is considered with the recognition of clinically apparent, macroscopic nodal disease through radiographic analysis including US
• Therapeutic compartmental central and/or lateral neck dissection in a previously operated compartment, sparing uninvolved vital structures, should be performed for patients with biopsy-proven persistent or recurrent disease for central neck nodes ≥8 mm and lateral neck nodes ≥10 mm in the smallest dimension that can be localized on anatomic imaging.
• For nodal surgery, because of the increased risk of recurrence with focal “berry-picking” techniques, compartmental surgery is recommended
• When technically feasible, surgery for aerodigestive invasive disease is recommended in combination with RAI and/or EBRT.
• For tumors that invade the upper aerodigestive tract, surgery combined with additional therapy such as 131I and/or external beam radiation therapy is generally advised
• Patients receiving therapeutic doses of RAI should have baseline complete blood count and assessment of renal function.
• Patients with xerostomia are at increased risk of dental caries and should discuss preventive strategies with their dental/oral health professional.
• Treatment of a specific metastatic area must be considered in light of the patient's performance status and other sites of disease; for example, 5%–20% of patients with distant metastases die from progressive cervical disease:
  • RAI therapy of iodine-avid bone metastases has been associated with improved survival and should be employed, although RAI is rarely curative.
  • Pulmonary micrometastases should be treated with RAI therapy and RAI therapy should be repeated every 6–12 months as long as disease continues to concentrate RAI and respond clinically

Don'ts

• Do not administer radioactive iodine to pregnant women
• Do not administer radioactive iodine to nursing women

References