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. The major causes of thyroid nodule development include, multinodular (sporadic) goiter, Hashimoto's thyroiditis, cysts, macrofollicular/microfollicular adenomas, childhood radioiodine exposure, familial history, and gene mutations. Neck masses can be mistaken for thyroid nodules. The most important neck masses that can be mistaken with thyroid nodules include, thyroglossal duct cyst, parathyroid cancer, parathyroid cyst, and branchial cleft cyst. While the diagnosis of a thyroid nodule is established, thyroid nodule should be differentiated based on benign or malignant features and the type of nodule. Common risk factors associated with thyroid nodules include, older age, iodine deficiency, previous history of iodine deficiency and hypothyroidism, living in iodine deficient areas, family history of autoimmune diseases, multiparity, and smoking. A solitary thyroid nodule may become symptomatic if it grows rapidly due to hemorrhage or malignancies, invades laryngeal nerves, compressing nearby structures, and secretory nodules that produce TSH. Thyroid nodules may be a manifestation of thyroid cancer, that usually develops in the 6th decade of life, and start with symptoms such as weight loss, fatigue, and hoarseness. Without treatment, the patient with benign nodules may remain asymptomatic, while the patients with thyroid neoplasm may develop distant metastasis, which may eventually lead to death. The most common complications of thyroid nodules are hoarseness, horner's syndrome, nodule rupture, needle track seeding, hemorrhage/hematoma, dysphagia, upper airway obstruction, pain, skin burn, vasovagal reaction, hypothyroidism, transient thyrotoxicosis, anaphylactic reaction, thromboembolism, and pneumothorax. Physical examination should focus on the thyroid gland and the lateral and central neck and should assess for supraclavicular and submandibular adenopathy. In case of active hot thyroid nodules that produce thyroid hormones, antithyroid drugs should be administered, that include beta-blockers, antithyroid drugs (methimazole,carbimazole,propylthiouracil), radioactive iodine, and thyroidectomy. If the nodule excision treatment (lobectomy, isthmectomy, and total thyroidectomy) is not curative, then treatment with postoperative radioactive iodine (RAI) remnant ablation and recombinant human TSH–mediated therapy is recommended. Surgical management of thyroid nodule is performed in case of non-diagnostic or suspicious biopsy, for removal of primary thyroid cancer or for thyroid cancer staging for radioactive ablation and serum thyroglobulin monitoring. Primary prevention of thyroid nodule is aimed at prevention of thyroid cancer. Avoidance of exposure to radiation and monitoring the population with an increased risk of development of a malignant thyroid nodule play major roles in primary prevention. Secondary prevention of thyroid nodules focuses on prevention of recurrence of nodules. Different prevention strategies may be used depending upon whether the nodule is benign or malignant. In case of a malignant nodule, the major focus is on the prevention of recurrence after removal of a primary nodule. Post-operative periodic monitoring with serum thyroglobulin levels, radioactive iodine scanning, neck ultrasound and thyroid stimulating hormone (TSH) may decrease the chances of recurrence.

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

• Order serum thyroglobulin periodically during follow-up of patients with differentiated thyroid cancer who have undergone less than total thyroidectomy
• Order serum thyroglobulin periodically during follow-up of patients with differentiated thyroid cancer who have had a total thyroidectomy but not radioactive iodine ablation

Cervical ultrasound

• Perform neck ultrasound to evaluate thyroid 6–12 months following surgery

18FDG-PET scanning

• Consider 18FDG-PET scanning in high-risk differentiated thyroid cancer patients with elevated serum thyroglobulin (generally >10 ng/mL) and negative radioactive iodine imaging

CT scans

• Order chest CT scan with or without intravenous contrast in high-risk differentiated thyroid cancer patients with elevated serum thyroglobulin (generally >10 ng/mL) or rising thyroglobulin antibodies with or without negative radioactive iodine imaging

TSH range

• Maintain serum TSH below 0.1 mU/L in patients with a structural incomplete response to therapy, indefinitely in the absence of specific contraindications
• Maintain serum TSH between 0.5-2 mU/L in patients with an excellent or indeterminate response to therapy, especially those at low risk for recurrence

Surgery for nodal disease

• Perform surgery in patients with clinically apparent, macroscopic nodal disease
• Perform therapeutic compartmental central and/or lateral neck dissection in a previously operated compartment, in patients with biopsy-proven persistent or recurrent disease for central neck nodes ≥8 mm and lateral neck nodes ≥10 mm
• Perform compartmental surgery
• Perform combination of surgery and radioactive iodine and/or external beam radiation therapy (EBRT) in patients with aerodigestive invasive disease
• Order complete blood count and assessment of renal function before administration of radioactive iodine
• Discuss preventive strategies for dental caries with patients with xerostomia

Radioactive iodine therapy

• Order pregnancy test before radioactive iodine administration
• Administer radioactive iodine therapy in patients with iodine-avid bone metastases
• Administer radioactive iodine therapy in patients with pulmonary micrometastases and every 6-12 months

Don'ts

• Do not administer radioactive iodine to pregnant women
• Do not administer radioactive iodine to nursing women
• Do not perform surgery with focal “berry-picking” techniques

References