Thyroid nodule resident survival guide

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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) goiterHashimoto's thyroiditiscysts, 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 lossfatigue, 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 hoarsenesshorner's syndrome, nodule rupture, needle track seeding, hemorrhage/hematomadysphagiaupper airway obstructionpainskin burn, vasovagal reactionhypothyroidism, transient thyrotoxicosisanaphylactic reactionthromboembolism, 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 hormonesantithyroid drugs should be administered, that include beta-blockers, antithyroid drugs (methimazole,carbimazole,propylthiouracil), radioactive iodine, and thyroidectomy. If the nodule excision treatment (lobectomyisthmectomy, 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:

 
 
 
 
 
 
 
Thyroid nodule classification
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bethesda classification system
 
 
 
 
 
 
 
 
 
 
TIRAD classification system
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Based on thyroid cytopathology
 
 
 
 
 
 
 
 
 
 
Based on sonographic features
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Benign
•Nondiagnostic or Unsatisfactory
•Follicular lesion of undetermined significance
Atypia of undetermined significance
•Follicular neoplasm
•Suspicious for a follicular neoplasm
Malignant
 
 
 
 
 
 
 
 
 
 
•TIRADS 1=Normal thyroid gland
•TIRADS 2=Benign lesions
•TIRADS 3=Probably benign lesions
•TIRADS 4= Contain 1-4 suspicious features
•TIRADS 5=Contain all five suspicious features
•TIRADS 6=Biopsy proven malignancy
 
 
 
 
 
 
 
Differentiated and anaplastic thyroid carcinoma
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TNM staging AJCC UICC 2017
 
 
 
 
 
Classification based on their origin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•Primary tumor (T)
•Regional lymph nodes (N)
•Distant metastasis (M)
 
 
Nonmedullary (epithelial) thyroid cancers (NMTCs)
•Papillary cell tumors
•Follicular tumors
•Hurthle cell tumors
•Anaplastic tumors
 
 
 
Medullary thyroid cancers
 
 

Causes

Life-threatening causes

The most important genes which can lead to thyroid cancer include:[1][2][3]

Causes of malignant nodule mutations:

Common causes

The most important causes of thyroid nodule development include:[4][5][6]

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

Cervical ultrasound

18FDG-PET scanning

CT scans

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

Radioactive iodine therapy

Don'ts

References

  1. Bomeli SR, LeBeau SO, Ferris RL (2010). "Evaluation of a thyroid nodule". Otolaryngol. Clin. North Am. 43 (2): 229–38, vii. doi:10.1016/j.otc.2010.01.002. PMC 2879398. PMID 20510711.
  2. Jena A, Patnayak R, Prakash J, Sachan A, Suresh V, Lakshmi AY (2015). "Malignancy in solitary thyroid nodule: A clinicoradiopathological evaluation". Indian J Endocrinol Metab. 19 (4): 498–503. doi:10.4103/2230-8210.159056. PMC 4481656. PMID 26180765.
  3. Chibishev A, Simonovska N, Shikole A (2010). "Post-corrosive injuries of upper gastrointestinal tract". Prilozi. 31 (1): 297–316. PMID 20693948.
  4. Bomeli SR, LeBeau SO, Ferris RL (2010). "Evaluation of a thyroid nodule". Otolaryngol. Clin. North Am. 43 (2): 229–38, vii. doi:10.1016/j.otc.2010.01.002. PMC 2879398. PMID 20510711.
  5. Jena A, Patnayak R, Prakash J, Sachan A, Suresh V, Lakshmi AY (2015). "Malignancy in solitary thyroid nodule: A clinicoradiopathological evaluation". Indian J Endocrinol Metab. 19 (4): 498–503. doi:10.4103/2230-8210.159056. PMC 4481656. PMID 26180765.
  6. Chibishev A, Simonovska N, Shikole A (2010). "Post-corrosive injuries of upper gastrointestinal tract". Prilozi. 31 (1): 297–316. PMID 20693948.

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