Thyroid nodule

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Thyroid nodule
Ultrasound Scan ND 0124141638 1428320.png
Ultrasound artifacts showing a "comet tail" from a colloid nodule indicate a benign nodule
Specialty ENT surgery, oncology

Thyroid nodules are nodules (raised areas of tissue or fluid) which commonly arise within an otherwise normal thyroid gland. [1] They may be hyperplastic or tumorous, but only a small percentage of thyroid tumors are malignant. Small, asymptomatic nodules are common, and often go unnoticed. [2] Nodules that grow larger or produce symptoms may eventually need medical care. A goitre may have one nodule – uninodular, multiple nodules – multinodular, or be diffuse.

Contents

Signs and symptoms

Often these abnormal growths of thyroid tissue are located at the edge of the thyroid gland and can be felt as a lump in the throat. When they are large, they can sometimes be seen as a lump in the front of the neck.[ citation needed ]

Sometimes a thyroid nodule presents as a fluid-filled cavity called a thyroid cyst. Often, solid components are mixed with the fluid. Thyroid cysts most commonly result from degenerating thyroid adenomas, which are benign, but they occasionally contain malignant solid components. [3]

Diagnosis

After a nodule is found during a physical examination, a referral to an endocrinologist, a thyroidologist or otolaryngologist may occur. Most commonly an ultrasound is performed to confirm the presence of a nodule, and assess the status of the whole gland. Measurement of thyroid stimulating hormone and anti-thyroid antibodies will help decide if there is a functional thyroid disease such as Hashimoto's thyroiditis present, a known cause of a benign nodular goitre. [4] Fine needle biopsy for cytopathology is also used. [5] [6] [7]

Thyroid nodules are extremely common in young adults and children. Almost 50% of people have had one, but they are usually only detected by a physician during the course of a health examination or fortuitously discovered during the investigation of an unrelated condition. [8]

Workup of incidental nodules

The American College of Radiology recommends the following workup for thyroid nodules as incidental imaging findings on CT, MRI or PET-CT: [9]

Suggested workups by nodule characteristics
FeaturesWorkup
  • High PET signal or
  • Local invasiveness or
  • Suspicious lymph nodes
Very likely ultrasonography
Multiple nodulesLikely ultrasonography
Solitary nodule in person younger than 35 years old
  • Likely ultrasonography if at least 1 cm large in adults, or for any size in children
  • None needed if less than 1 cm in adults
Solitary nodule in person at least 35 years old
  • Likely ultrasonography if at least 1.5 cm large
  • None needed if less than 1.5 cm

Ultrasound

Ultrasound imaging is useful as the first-line, non-invasive investigation in determining the size, texture, position, and vascularity of a nodule, accessing lymph nodes metastasis in the neck, and for guiding fine needle aspiration cytology (FNAC) or biopsy. Ultrasonographic findings will also guide the indication to biopsy and the long term follow-up. [10] High frequency transducer (7–12 MHz) is used to scan the thyroid nodule, while taking cross-sectional and longitudinal sections during scan. Suspicious findings in a nodule are hypoechoic, ill-defined margins, absence of peripheral halo or irregular margin, fine, punctate microcalcifications, presence of solid nodule, high levels of irregular blood flow within the nodule [11] or "taller-than-wide sign" (anterior-posterior diameter is greater than transverse diameter of a nodule). Features of benign lesion are: hyperechoic, having coarse, dysmorphic or curvilinear calcifications, comet tail artifact (reflection of a highly calcified object), absence of blood flow in the nodule, and presence of cystic (fluid-filled) nodule. However, the presence of solitary or multiple nodules is not a good predictor of malignancy. Malignancy is only diagnosed when ultrasound findings and FNAC report are suggestive of malignancy. [11] The TI-RADS (Thyroid Imaging Reporting and Data Systems) are sonographic classification systems which describe the suspicious findings of thyroid nodules. [12] It was first proposed by Horvath et al., [13] based on the BI-RADS (Breast Imaging Reporting and Data System) concept. Several systems were subsequently proposed and adopted by international scientific societies. Their main aims are to characterize the risk of malignancy of nodules to better select nodules to submit to fine-needle aspiration cytology. [14] TI-RADS developed by the American College of Radiology (ACR) guides clinicians in deciding which nodules require FNAC and in planning follow-up. Various online tools have been developed to assist in applying these criteria to clinical practice .

Another imaging modality, which is ultrasound elastography, is also useful in diagnosing thyroid malignancy especially for follicular thyroid cancer. However, it is limited by the presence of adequate amount of normal tissue around the lesion, calcified shell around a nodule, cystic nodules, coalescent nodules. [15]

Fine needle biopsy

Fine Needle Aspiration Cytology (FNAC) is a cheap, simple, and safe method in obtaining cytological specimens for diagnosis by using a needle and a syringe. [16] The indications to do FNAC are: nodules more than 1 cm with two ultrasound criteria suggestive of malignancy, nodules of any size with extracapsular extension or lymph nodes enlargement with unknown source, any sizes of nodules with history of head and neck radiation, family history of thyroid carcinoma in two or more first degree relatives, multiple endocrine neoplasia type II, and increased calcitonin levels. However, increased calcitonin levels can also be attributable to smoking, chronic alcohol consumption, usage of proton pump inhibitors, and renal failure. [17] The Bethesda System for Reporting Thyroid Cytopathology is the system used to report whether the thyroid cytological specimen is benign or malignant. It can be divided into six categories:

Bethesda system
CategoryDescriptionRisk of malignancy [18] Recommendation [18]
INon diagnostic/unsatisfactoryRepeating FNAC with ultrasound-guidance in more than 3 months
IIBenign (colloid and follicular cells)0–3%Clinical follow-up
IIIAtypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) (follicular or lymphoid cells with atypical features)5–15%Repeating FNAC
IVFollicular nodule/suspicious follicular nodule (cell crowding, micro follicles, dispersed isolated cells, scant colloid)15–30%Surgical lobectomy
VSuspicious for malignancy60–75%Surgical lobectomy or near-total thyroidectomy
VIMalignant97–99%Near-total thyroidectomy

Blood tests

Blood tests may be done prior to or in lieu of a biopsy. The possibility of a nodule which secretes thyroid hormone (which is less likely to be cancer) or hypothyroidism is investigated by measuring thyroid stimulating hormone (TSH), and the thyroid hormones thyroxine (T4) and triiodothyronine (T3). Tests for serum thyroid autoantibodies are sometimes done as these may indicate autoimmune thyroid disease (which can mimic nodular disease).[ citation needed ]

Other imaging

Thyroid scan Thyroid scan.jpg
Thyroid scan

A thyroid scan using a radioactive iodine uptake test can be used in viewing the thyroid. [19] A scan using iodine-123 showing a hot nodule, accompanied by a lower than normal TSH, is strong evidence that the nodule is not cancerous, as most hot nodules are benign. [20]

Computed tomography of the thyroid plays an important role in the evaluation of thyroid cancer. [21] CT scans often incidentally find thyroid abnormalities, and thereby practically becomes the first investigation modality. [21]

Malignancy

Only a small percentage of lumps in the neck are malignant (around 4 – 6.5% [22] ), and most thyroid nodules are benign colloid nodules.

There are many factors to consider when diagnosing a malignant lump. Trouble swallowing or speaking, swollen cervical lymph nodes or a firm, immobile nodule are more indicative of malignancy, whereas a family history of autoimmune disease or goiter, thyroid hormonal dysfunction or a soft, painful nodule are more indicative of benignancy.[ citation needed ]

The prevalence of cancer is higher in males, patients under 20 years old or over 70 years old, and patients with a history of head and neck irradiation or a family history of thyroid cancer. [23]

Solitary thyroid nodule

Relative incidences of histopathologic diagnoses of solitary thyroid nodules that have undergone fine needle aspiration Relative incidences of histopathologic diagnoses of solitary thyroid nodules.png
Relative incidences of histopathologic diagnoses of solitary thyroid nodules that have undergone fine needle aspiration

Risks for cancer

Solitary thyroid nodules are more common in females yet more worrisome in males. Other associations with neoplastic nodules are family history of thyroid cancer and prior radiation to the head and neck. Solitary thyroid nodules are mostly benign colloid nodules. The second most common type is follicular adenoma. [25]

Radiation exposure to the head and neck may be for historic indications such as tonsillar and adenoid hypertrophy, "enlarged thymus", acne vulgaris, or existent indications such as Hodgkin's lymphoma. Children living near the Chernobyl nuclear power plant during the catastrophe of 1986 experienced a 60-fold increase in the incidence of thyroid cancer. Thyroid cancer arising in the background of radiation is often multifocal with a high incidence of lymph node metastasis and has a poor prognosis.[ citation needed ]

Signs and symptoms

Worrisome sign and symptoms include voice hoarseness, rapid increase in size, compressive symptoms (such as dyspnoea or dysphagia) and appearance of lymphadenopathy.[ citation needed ]

Investigations

Thyroid scan

85% of nodules are cold nodules, and 5–8% of cold and warm nodules are malignant. [28]

5% of nodules are hot. Malignancy is virtually non-existent in hot nodules. [29]

Surgery

Surgery (thyroidectomy) may be indicated in some instances:

Minimally-invasive procedures

Non-surgical, minimally invasive ultrasound-guided techniques are used for the treatment of large, symptomatic nodules. They include percutaneous ethanol injection, laser thermal ablation, radiofrequency ablation, high intensity focused ultrasound (HIFU), and percutaneous microwave ablation. [30]

HIFU has recently proved its effectiveness in treating benign thyroid nodules. This method is noninvasive, without general anesthesia and is performed in an ambulatory setting. Ultrasound waves are focused and produce heat enabling them to destroy thyroid nodules. [31] Focused ultrasounds have been used to treat other benign tumors, such as breast fibroadenomas and fibroid disease in the uterus.[ citation needed ]

Treatment

Levothyroxine (T4) is a prohormone that peripheral tissues convert to the primary active thyroid hormone, triiodothyronine (T3). Hypothyroid patients normally take it once per day.

Autonomous thyroid nodule

An autonomous thyroid nodule or "hot nodule" is one that has thyroid function independent of the homeostatic control of the HPT axis (hypothalamic–pituitary–thyroid axis). According to a 1993 article, such nodules need to be treated only if they become toxic; surgical excision (thyroidectomy), radioiodine therapy, or both may be used. [32]

See also

Related Research Articles

<span class="mw-page-title-main">Thyroid</span> Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the isthmus. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid.

<span class="mw-page-title-main">Thyroid neoplasm</span> Tumor of the thyroid gland

Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm, such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. The estimated number of new cases of thyroid cancer in the United States in 2023 is 43,720 compared to only 2,120 deaths. Of all thyroid nodules discovered, only about 5 percent are cancerous, and under 3 percent of those result in fatalities.

<span class="mw-page-title-main">Cytopathology</span> A branch of pathology that studies and diagnoses diseases on the cellular level

Cytopathology is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by George Nicolas Papanicolaou in 1928. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to histopathology, which studies whole tissues. Cytopathology is frequently, less precisely, called "cytology", which means "the study of cells".

In medical or research imaging, an incidental imaging finding is an unanticipated finding which is not related to the original diagnostic inquiry. As with other types of incidental medical findings, they may represent a diagnostic, ethical, and philosophical dilemma because their significance is unclear. While some coincidental findings may lead to beneficial diagnoses, others may lead to overdiagnosis that results in unnecessary testing and treatment, sometimes called the "cascade effect".

<span class="mw-page-title-main">Fine-needle aspiration</span> Diagnostic medical procedure

Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin, hollow needle is inserted into the mass for sampling of cells that, after being stained, are examined under a microscope (biopsy). The sampling and biopsy considered together are called fine-needle aspiration biopsy (FNAB) or fine-needle aspiration cytology (FNAC). Fine-needle aspiration biopsies are very safe minor surgical procedures. Often, a major surgical biopsy can be avoided by performing a needle aspiration biopsy instead, eliminating the need for hospitalization. In 1981, the first fine-needle aspiration biopsy in the United States was done at Maimonides Medical Center. The modern procedure is widely used in the diagnosis of cancer and inflammatory conditions. Fine needle aspiration is generally considered a safe procedure. Complications are infrequent.

<span class="mw-page-title-main">Thyroid disease</span> Medical condition

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

<span class="mw-page-title-main">Pleomorphic adenoma</span> Medical condition

Pleomorphic adenoma is a common benign salivary gland neoplasm characterised by neoplastic proliferation of epithelial (ductal) cells along with myoepithelial components, having a malignant potentiality. It is the most common type of salivary gland tumor and the most common tumor of the parotid gland. It derives its name from the architectural Pleomorphism seen by light microscopy. It is also known as "Mixed tumor, salivary gland type", which refers to its dual origin from epithelial and myoepithelial elements as opposed to its pleomorphic appearance.

<span class="mw-page-title-main">Toxic multinodular goitre</span> Enlarged thyroid gland, causing symptoms of hyperthyroidism

Toxic multinodular goiter (TMNG), also known as multinodular toxic goiter (MNTG), is an active multinodular goiter associated with hyperthyroidism.

<span class="mw-page-title-main">Hürthle cell neoplasm</span> Medical condition

Hürthle cell neoplasm is a rare tumor of the thyroid, typically seen in women between the ages of 70 and 80 years old. When benign, it is called a Hürthle cell adenoma, and when malignant it is called a Hürthle cell carcinoma. Hürthle cell adenoma is characterized by a mass of benign Hürthle cells. Typically such a mass is removed because it is not easy to predict whether it will transform into the malignant counterpart of Hürthle cell carcinoma, which is a subtype of follicular thyroid cancer.

<span class="mw-page-title-main">Papillary thyroid cancer</span> Medical condition

Papillary thyroid cancer is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-differentiated, slow-growing, and localized, although it can metastasize.

<span class="mw-page-title-main">Breast cyst</span> Medical condition

A breast cyst is a cyst, a fluid-filled sac, within the breast. One breast can have one or more cysts. They are often described as round or oval lumps with distinct edges. In texture, a breast cyst usually feels like a soft grape or a water-filled balloon, but sometimes a breast cyst feels firm.

<span class="mw-page-title-main">Follicular thyroid cancer</span> Malignant tumor made of hormone-producing cells in the thyroid gland

Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Thyroid follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.

<span class="mw-page-title-main">Lung nodule</span> Medical condition

A lung nodule or pulmonary nodule is a relatively small focal density in the lung. A solitary pulmonary nodule (SPN) or coin lesion, is a mass in the lung smaller than three centimeters in diameter. A pulmonary micronodule has a diameter of less than three millimetres. There may also be multiple nodules.

The Bethesda system (TBS), officially called The Bethesda System for Reporting Cervical Cytology, is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results. It was introduced in 1988 and revised in 1991, 2001, and 2014. The name comes from the location of the conference, sponsored by the National Institutes of Health, that established the system.

<span class="mw-page-title-main">Thyroid cancer</span> Malignancy originating in the thyroid gland

Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck, difficulty swallowing or voice changes including hoarseness, or a feeling of something being in the throat due to mass effect from the tumor. However, most cases are asymptomatic. Cancer can also occur in the thyroid after spread from other locations, in which case it is not classified as thyroid cancer.

<span class="mw-page-title-main">Cervical lymphadenopathy</span> Disease of the lymph nodes

Cervical lymphadenopathy refers to lymphadenopathy of the cervical lymph nodes. The term lymphadenopathy strictly speaking refers to disease of the lymph nodes, though it is often used to describe the enlargement of the lymph nodes. Similarly, the term lymphadenitis refers to inflammation of a lymph node, but often it is used as a synonym of lymphadenopathy.

<span class="mw-page-title-main">Colloid nodule</span> Benign enlargement of thyroid tissue

Colloid nodules, also known as adenomatous nodules or colloid nodular goiter are benign, noncancerous enlargement of thyroid tissue. Although they may grow large, and there may be more than one, they are not malignant and they will not spread beyond the thyroid gland. Colloid nodules are the most common kind of thyroid nodule.

<span class="mw-page-title-main">Triple test score</span>

The triple test score is a diagnostic tool for examining potentially cancerous breasts. Diagnostic accuracy of the triple test score is nearly 100%. Scoring includes using the procedures of physical examination, mammography and needle biopsy. If the results of a triple test score are greater than five, an excisional biopsy is indicated.

<span class="mw-page-title-main">Noninvasive follicular thyroid neoplasm with papillary-like nuclear features</span>

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor that was previously classified as an encapsulated follicular variant of papillary thyroid carcinoma, necessitating a new classification as it was recognized that encapsulated tumors without invasion have an indolent behavior, and may be over-treated if classified as a type of cancer.

In CT scan of the thyroid, focal and diffuse thyroid abnormalities are commonly encountered. These findings can often lead to a diagnostic dilemma, as the CT reflects nonspecific appearances. Ultrasound (US) examination has a superior spatial resolution and is considered the modality of choice for thyroid evaluation. Nevertheless, CT detects incidental thyroid nodules (ITNs) and plays an important role in the evaluation of thyroid cancer.

References

  1. "New York Thyroid Center: Thyroid Nodules". Archived from the original on 2010-09-17.
  2. Vanderpump MP (2011). "The epidemiology of thyroid disease". British Medical Bulletin. 99 (1): 39–51. doi:10.1093/bmb/ldr030. PMID   21893493.
  3. "Symptoms and causes - Mayo Clinic". Mayo Clinic.
  4. Bennedbaek FN, Perrild H, Hegedüs L (March 1999). "Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey". Clinical Endocrinology. 50 (3): 357–363. doi: 10.1046/j.1365-2265.1999.00663.x . PMID   10435062. S2CID   21514672.
  5. Ravetto C, Colombo L, Dottorini ME (December 2000). "Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients". Cancer. 90 (6): 357–363. doi: 10.1002/1097-0142(20001225)90:6<357::AID-CNCR6>3.0.CO;2-4 . PMID   11156519.
  6. "Thyroid Nodule". www.meddean.luc.edu.
  7. Grani G, Sponziello M, Pecce V, Ramundo V, Durante C (September 2020). "Contemporary Thyroid Nodule Evaluation and Management". The Journal of Clinical Endocrinology and Metabolism. 105 (9): 2869–2883. doi:10.1210/clinem/dgaa322. PMC   7365695 . PMID   32491169.
  8. Russ G, Leboulleux S, Leenhardt L, Hegedüs L (September 2014). "Thyroid incidentalomas: epidemiology, risk stratification with ultrasound and workup". European Thyroid Journal. 3 (3): 154–163. doi:10.1159/000365289. PMC   4224250 . PMID   25538897.
  9. Jenny Hoang (2013-11-05). "Reporting of incidental thyroid nodules on CT and MRI". Radiopaedia ., citing:
    • Hoang JK, Langer JE, Middleton WD, Wu CC, Hammers LW, Cronan JJ, et al. (February 2015). "Managing incidental thyroid nodules detected on imaging: white paper of the ACR Incidental Thyroid Findings Committee". Journal of the American College of Radiology. 12 (2): 143–150. doi:10.1016/j.jacr.2014.09.038. PMID   25456025.
  10. Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS (March 2018). "The Diagnosis and Management of Thyroid Nodules: A Review". JAMA. 319 (9): 914–924. doi:10.1001/jama.2018.0898. PMID   29509871. S2CID   5042725.
  11. 1 2 Wong KT, Ahuja AT (December 2005). "Ultrasound of thyroid cancer". Cancer Imaging. 5 (1): 157–166. doi:10.1102/1470-7330.2005.0110. PMC   1665239 . PMID   16361145.
  12. Fernández Sánchez J (July 2014). "Clasificación TI-RADS de los nódulos tiroideos en base a una escala de puntuación modificada con respecto a los criterios ecográficos de malignidad". Revista Argentina de Radiología. 78 (3): 138–148. doi: 10.1016/j.rard.2014.07.015 .
  13. Horvath E, Majlis S, Rossi R, Franco C, Niedmann JP, Castro A, Dominguez M (May 2009). "An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management". The Journal of Clinical Endocrinology and Metabolism. 94 (5): 1748–1751. doi: 10.1210/jc.2008-1724 . PMID   19276237.
  14. Grani G, Lamartina L, Ascoli V, Bosco D, Biffoni M, Giacomelli L, et al. (January 2019). "Reducing the Number of Unnecessary Thyroid Biopsies While Improving Diagnostic Accuracy: Toward the "Right" TIRADS". The Journal of Clinical Endocrinology and Metabolism. 104 (1): 95–102. doi: 10.1210/jc.2018-01674 . PMID   30299457.
  15. Soto GD, Halperin I, Squarcia M, Lomeña F, Domingo MP (10 September 2010). "Update in thyroid imaging. The expanding world of thyroid imaging and its translation to clinical practice". Hormones. 9 (4): 287–298. doi: 10.14310/horm.2002.1279 . PMID   21112859. S2CID   15979225.
  16. Diana SD, Hossein G. "Fine-Needle Aspiration Biopsy of the Thyroid Gland". Thyroid Disease Manager. Archived from the original on 12 July 2017. Retrieved 16 October 2017.
  17. Feldkamp J, Führer D, Luster M, Musholt TJ, Spitzweg C, Schott M (May 2016). "Fine Needle Aspiration in the Investigation of Thyroid Nodules". Deutsches Ärzteblatt International (in German). 113 (20). Deutsches rzteblatt: 353–359. doi:10.3238/arztebl.2016.0353. PMC   4906830 . PMID   27294815.
  18. 1 2 Renuka IV, Saila Bala G, Aparna C, Kumari R, Sumalatha K (December 2012). "The bethesda system for reporting thyroid cytopathology: interpretation and guidelines in surgical treatment". Indian Journal of Otolaryngology and Head and Neck Surgery. 64 (4): 305–311. doi:10.1007/s12070-011-0289-4. PMC   3477437 . PMID   24294568.
  19. MedlinePlus Encyclopedia : Thyroid scan
  20. Grani, Giorgio; Sponziello, Marialuisa; Filetti, Sebastiano; Durante, Cosimo (2024-08-16). "Thyroid nodules: diagnosis and management". Nature Reviews Endocrinology. doi:10.1038/s41574-024-01025-4. ISSN   1759-5029.
  21. 1 2 Bin Saeedan M, Aljohani IM, Khushaim AO, Bukhari SQ, Elnaas ST (August 2016). "Thyroid computed tomography imaging: pictorial review of variable pathologies". Insights into Imaging. 7 (4): 601–617. doi:10.1007/s13244-016-0506-5. PMC   4956631 . PMID   27271508. Creative Commons Attribution 4.0 International License
  22. "UpToDate".
  23. Thyroid Nodule at eMedicine
  24. Diagram by Mikael Häggström, MD. Source data: Arul P, Masilamani S (2015). "A correlative study of solitary thyroid nodules using the bethesda system for reporting thyroid cytopathology". J Cancer Res Ther. 11 (3): 617–22. doi: 10.4103/0973-1482.157302 . PMID   26458591.
  25. Schwartz 7th/e page 1679,1678
  26. Ali SZ, Cibas ES (2016). "The Bethesda System for Reporting Thyroid Cytopathology II". Acta Cytologica. 60 (5): 397–398. doi: 10.1159/000451071 . PMID   27788511. S2CID   32693137.
  27. Grani G, Calvanese A, Carbotta G, D'Alessandri M, Nesca A, Bianchini M, et al. (January 2013). "Intrinsic factors affecting adequacy of thyroid nodule fine-needle aspiration cytology". Clinical Endocrinology. 78 (1): 141–144. doi:10.1111/j.1365-2265.2012.04507.x. PMID   22812685. S2CID   205287747.
  28. Gates JD, Benavides LC, Shriver CD, Peoples GE, Stojadinovic A (August 2009). "Preoperative thyroid ultrasound in all patients undergoing parathyroidectomy?". The Journal of Surgical Research. 155 (2): 254–260. doi:10.1016/j.jss.2008.09.012. PMID   19482296.
  29. Robbins pathology 8ed page 767
  30. Tumino D, Grani G, Di Stefano M, Di Mauro M, Scutari M, Rago T, et al. (2019). "Nodular Thyroid Disease in the Era of Precision Medicine". Frontiers in Endocrinology. 10: 907. doi: 10.3389/fendo.2019.00907 . PMC   6989479 . PMID   32038482.
  31. "Echotherapy for thyroid nodules". Echotherapy.
  32. Vigneri R, Catalfamo R, Freni V, Giuffrida D, Gullo D, Ippolito A, et al. (December 1993). "[Physiopathology of the autonomous thyroid nodule]". Minerva Endocrinologica. 18 (4): 143–145. PMID   8190053.