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thyroid nodule

Etiology: 1) benign a) thyroid adenoma - colloid nodule (colloid adenoma) - follicular adenoma - Hurthle cell adenoma b) thyroid cyst - thyroglossal duct cyst - branchial cyst - dermoid cyst - colloid cyst - hemorrhagic cyst c) pyramidal lobe of thyroid d) lipoma e) teratoma f) cervical lymphadenopathy 2) malignant a) thyroid carcinoma - risk same for solitary nodules vs multinodular goiter - papillary thyroid cancer - follicular thyroid cancer - medullary thyroid cancer - anaplastic thyroid cancer b) primary thyroid lymphoma c) metastatic cancer - breast cancer - renal cell carcinoma - melanoma d) sarcoma * also see differential diagnosis Epidemiology: - 4-7% of population (by palpation) [11]; 1-5% [3] - incidence may be much higher (19-67%) by ultrasound [11] Pathology: - most thyroid nodules are benign - majority of asymptomatic thyroid nodules do not grow significantly or progress to cancer [9] - 5-15% (~10% [3]) of thyroid nodules are malignant Clinical manifestations: - palpable thyroid nodule or nodules - symptoms of hyperthyroidism (autonomous thyroid adenoma) - symptoms of hypothyroidism (Hashimoto's thyroiditis) Laboratory: 1) serum thyroid-stimulating hormone (serum TSH) a) may be low (autonomous thyroid adenoma) b) may be high (Hashimoto's thyroiditis) 2) serum T4 & free thyroxine index or free T4 3) serum T3 & free T3 4) serum calcium - serum calcitonin if hypercalcemia or family history of thyroid cancer or MEN1 [2] 5) serum thyroglobulin not useful for distinguishing benign nodule from thyroid carcinoma [3] 6) cytology from fine-needle aspiration (FNAC) a) all thyroid nodules associated with normal serum TSH b) all cold nodules within a multinodular goiter Special laboratory: 1) ultrasound (US) a) all thyroid nodules with normal or elevated serum TSH - exception: 'hot nodules' with low serum TSH - in that case thyroid scintigraphy with I-123 indicated b) ultrasound prior to fine needle aspiration to ensure no additional nonpalpable nodules & to assess cervical lymph nodes [3] c) may identify simple cysts, but yield is low & specificity for malignancy is low d) microcalcification within a nodule, nodules > 2 cm & completely solid nodules suggest malignancy [7] e) repeat ultrasonography all thyroid nodules after negative FNA [3] - 6-12 months if high-suspicion, 12-24 months for lower suspicion [3] 2) fine needle aspiration (FNA) a) in no case is FNA indicated prior to imaging, ultrasound or scintigraphy b) not indicated for 'hot nodules' (low serum TSH) - low likelihood of malignancy c) thyroid nodules > 1 cm [3] &/or worrisome features d) worrisome features: irregular border, central intranodular vascularity, microcalcifications, hypoechogenicity, lymphadenopathy, or extrathyroidal extension, childhood radiation exposure, familial thyroid cancer syndrome e) analyze aspirate for BRAF mutation when diagnosis is indeterminate (papillary thyroid carcinoma) f) analyze for RET mutation g) case of follicular thyroid neoplasm 1] 15-30% chance of follicular thyroid carcinoma 2] carcinoma cannot be distinguished from adenoma on FNA 3] thyroid lobectomy or total thyroidectomy indicated h) in cases of nondiagnostic FNA, 2.3% later diagnosed with thyroid carcinoma [8] Radiology: - thyroid scintigraphy/radionuclide scan with I-123 (see 'hot nodule') - when serum T3 & T4 are elevated &/or serum TSH is low or undetectable - 'hot nodules' virtually never malignant - identifies 'cold nodule in a multinodular goiter for FNA & cytology * scintigraphy contraindicated during pregnancy Complications: - 8-16% of thyroid nodules harbor thyroid cancer [11] Differential diagnosis: 1) Hashimoto's thyroiditis feels firm with multiple small nodules 2) colloid adenomas may be soft 3) tenderness suggests hemorrhage into a colloid adenoma 4) fluctuance suggests cystic changes, most likely from hemorrhage or necrosis of a colloid adenoma 5) thyroid carcinoma - rapid growth, firmness of nodule, fixation to adjacent structures, vocal cord paralysis, enlarged regional lymph nodes suggest malignancy 6) male age < 20 or > 60, history of radiation, solitary nodule & nodule diameter > 4 cm are also risk factors for malignancy 7) female age > 20, soft & rubbery nodule < 4 cm suggest benign nodule Management: 1) fine-needle aspiration (FNA) of solitary thyroid nodule in euthyroid patient to rule out malignancy - not indicated in hyperthyroid patients with 'hot nodule' - complex thyroid nodules of 1.5-2 cm should be aspirated in pregnant women [4] - risk of thyroid carcinoma very low after FNA reveals benign nodule [6] - guidelines for followup of benign nodules not established [6] 2) thyroidectomy indicated if: a) cytology from FNA suggests malignant nodule b) continued nodule growth despite benign pathology on FNA c) non diagnostic results on repeat FNA d) large multinodular goiters with compressive symptoms e) FNA positive for RET mutation: most patients eventually develop medullary thyroid carcinoma 3) neck dissection indicated in patients with thyroid cancer & a) lymph node involvement b) large tumors with poor features c) medullary thyroid carcinoma 4) levothyroxine to suppress TSH is necessary after thyroidectomy a) TSH stimulates most papillary thyroid carcinomas & follicular thyroid carcinomas b) levothyroxine replacement needed in the absence of sufficient thyroid tissue 5) levothyroxine therapy to suppress TSH for 6-12 months if in doubt of diagnosis, then repeat FNA 6) use of levothyroxine to suppress TSH in patients with benign thyroid nodules is not indicated [3] 7) 131-I (radioactive iodine) ablation for hyperfunctioning 'hot nodules' identified by thyroid scintigraphy/radionuclide scan with I-123 - hemithyroidectomy is alternative

Related

multinodular goiter thyroid neoplasm (nodule)

Specific

cold nodule hot nodule; toxic thyroid adenoma thyroid cyst

General

thyroid disease nodule mass lesion

References

  1. Solomon DH, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  2. Rosai J et al, Atlas of Tumor Pathology: Tumors of the Thyroid Gland, AFIP 1992
  3. Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. De Groot L et al Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab August 1, 2012 97(8):2543 PMID: 22869843 http://jcem.endojournals.org/content/97/8/2543.abstract (corresponding NGC guideline withdrawn Feb 2018) - Stagnaro-Green A Optimal Care of the Pregnant Woman with Thyroid Disease J Clin Endocrinol Metab August 1, 2012 97(8):2619 PMID: 22869845 http://jcem.endojournals.org/content/97/8/2619.full
  5. Cooper DS, Doherty GM, Haugen BR et al American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov;19(11):1167-214 PMID: 19860577 http://online.liebertpub.com/doi/full/10.1089/thy.2009.0110
  6. Nou E et al. Determination of the optimal time interval for repeat evaluation after a benign thyroid nodule aspiration. J Clin Endocrinol Metab 2014 Feb; 99:510 PMID: 24276452 http://press.endocrine.org/doi/abs/10.1210/jc.2013-3160
  7. Brito JP, Morris JC, Montori VM. Thyroid cancer: zealous imaging has increased detection and treatment of low risk tumours. BMJ. 2013 Aug 27;347:f4706. PMID: 23982465
  8. Anderson TJT et al. Management of nodules with initially nondiagnostic results of thyroid fine-needle aspiration: Can we avoid repeat biopsy? Radiology 2014 Sep; 272:777 PMID: 24749714
  9. Durante C et al The Natural History of Benign Thyroid Nodules. JAMA. 2015;313(9):926-935 PMID: 25734734 http://jama.jamanetwork.com/article.aspx?articleid=2174027 - Cappola AR, Mandel SJ Improving the Long-term Management of Benign Thyroid Nodules. JAMA. 2015;313(9):903-904 PMID: 25734731 http://jama.jamanetwork.com/article.aspx?articleid=2174007
  10. Haugen BR et al for the American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2015 (nor yet peer-reviewed) http://online.liebertpub.com/doi/pdfplus/10.1089/thy.2015.0020
  11. Burman KD, Wartofsky L Thyroid Nodules N Engl J Med 2015; 373:2347-2356. December 10, 2015 PMID: 26650154 http://www.nejm.org/doi/full/10.1056/NEJMcp1415786
  12. Jameson JL. Minimizing unnecessary surgery for thyroid nodules. N Engl J Med. 2012 Aug 23;367(8):765-7 PMID: 22731671
  13. Hegedus L The Thyroid Nodule. N Engl J Med 2004; 351:1764-1771 PMID: 15496625 https://www.nejm.org/doi/full/10.1056/NEJMcp031436
  14. Haugen BR, Alexander EK, Bible KC et al 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. Review. PMID: 26462967 Free PMC Article
  15. Tessler FN, Middleton WD, Grant EG et al ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee. J Am Coll Radiol. 2017 May;14(5):587-595. Epub 2017 Apr 2. PMID: 28372962
  16. ARUP Consult: Thyroid Nodules Testing Algorithm https://arupconsult.com/algorithm/thyroid-nodules-testing-algorithm
  17. Valderrabano P, McIver B Evaluation and management of indeterminant thyroid nodules: the revolution of risk stratification beyond clinical diagnosis. Cancer Control. 2017; 24(5)1073274817729231 PMID: 28975825 PMCID: PMC5937245 Free PMC article
  18. Tamhane S, Gharib H Thyroid nodule update on diagnosis and management. Clin Diabetes Endocrinol. 2016 Oct 3;2:17. PMID: 28702251 Free PMC article. Review.