Thyroid nodule

Last updated
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]

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] 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 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 [17] Recommendation [17]
INon diagnostic/unsatisfactory-Repeating FNAC with ultrasound-guidance in more than 3 months
IIBenign (colloid and follicular cells)0 - 3%Clinical follow-up
IIIAtypia of undetermined significance/follicular lesion of undetermined significance (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. [18] 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.

Computed tomography of the thyroid plays an important role in the evaluation of thyroid cancer. [19] CT scans often incidentally find thyroid abnormalities, and thereby practically becomes the first investigation modality. [19]

Malignancy

Only a small percentage of lumps in the neck are malignant (around 4 – 6.5% [20] ), 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. [21]

Solitary thyroid nodule

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. Most common cause of solitary thyroid nodule is benign colloid nodules and second most common cause is follicular adenoma. [22]

Radiation exposure to the head and neck may be for historic indications such as tonsillar and adenoid hypertrophy, "enlarged thymus", acne vulgaris, or current indications such as Hodgkin's lymphoma. Children living near the Chernobyl nuclear power plant during the catastrophe of 1986 have 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. [25]

5% of nodules are hot. Malignancy is virtually non-existent in hot nodules. [26]

Surgery

Surgery (thyroidectomy) may be indicated in the following instances:

Minimally-invasive procedures

Non-surgical, minimally invasive ultrasound-guided techniques are now being 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. [27]

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 to destroy thyroid nodules. [28] 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. [29]

See also

Related Research Articles

Hyperthyroidism Thyroid gland disease that involves an overproduction of thyroid hormone.

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

Thyroid Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in the neck consisting of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyroid is located at the front of the neck, below the Adam's apple. 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. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T3) and thyroxine (T4) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis, and in children, growth and development. Calcitonin plays a role in calcium homeostasis. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.

Thyroid neoplasm

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 2010 is 44,670 compared to only 1,690 deaths. Of all thyroid nodules discovered, only about 5 percent are cancerous, and under 3 percent of those result in fatalities.

Cytopathology 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 finding is an unanticipated finding which is not related to the original diagnostic inquiry. As with other types of incidental findings, they may represent a diagnostic, ethical, and philosophical dilemma because the significance is unclear. While some coincidental findings may lead to beneficial diagnoses, others may lead to overdiagnosis in the form of unnecessary testing and treatment, i.e. the "cascade effect."

Fine-needle aspiration diagnostic procedure to investigate lumps using a thin needle, for histopathology or cytopathology

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. Today, this procedure is widely used in the diagnosis of cancer and inflammatory conditions.

Thyroid disease type of endocrine disease

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.

Pleomorphic adenoma gastrointestinal benign neoplasm that is a located in the salivary glands

Pleomorphic adenoma is a common benign salivary gland neoplasm characterised by neoplastic proliferation of parenchymatous glandular 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.

Hürthle cell adenoma is a rare benign tumor, typically seen in women between the ages of 70 and 80 years old. This 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, a subtype of follicular thyroid cancer called a Hürthle cell carcinoma.

Papillary thyroid cancer thyroid carcinoma that is characterized by the small mushroom shape of the tumor which has a stem attached to the epithelial layer

Papillary thyroid cancer or papillary thyroid carcinoma 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.

Fibrocystic breast changes Human disease

Fibrocystic breast changes is a condition of the breasts where there may be pain, breast cysts, and breast masses. The breasts may be described as "lumpy" or "doughy". Symptoms may worsen during certain parts of the menstrual cycle. It is not associated with cancer.

Follicular thyroid cancer thyroid carcinoma that has material basis in follicular cells

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.

Salivary gland tumour human disease

Salivary gland tumours or neoplasms are tumours that form in the tissues of salivary glands. The salivary glands are classified as major or minor. The major salivary glands consist of the parotid, submandibular, and sublingual glands. The minor salivary glands consist of 800-1000 small mucus-secreting glands located throughout the lining of the oral cavity.

Lung nodule human disease

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 3 centimeters in diameter. There may also be multiple nodules.

The Bethesda system (TBS) 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 that established the system.

Thyroid cancer endocrine gland cancer located in the thryoid gland located in the neck below the thyroid cartilage

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. Cancer can also occur in the thyroid after spread from other locations, in which case it is not classified as thyroid cancer.

Cervical lymphadenopathy

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.

Colloid nodule

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.

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 the 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", Br Med Bull, 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 (1999). "Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey". Clin. Endocrinol. 50 (3): 357–63. doi:10.1046/j.1365-2265.1999.00663.x. PMID   10435062. S2CID   21514672.
  5. Ravetto C, Colombo L, Dottorini ME (2000). "Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients". Cancer. 90 (6): 357–63. doi:10.1002/1097-0142(20001225)90:6<357::AID-CNCR6>3.0.CO;2-4. PMID   11156519.
  6. "Thyroid Nodule".
  7. Grani, Giorgio; Sponziello, Marialuisa; Pecce, Valeria; Ramundo, Valeria; Durante, Cosimo (2020-09-01). "Contemporary Thyroid Nodule Evaluation and Management". The Journal of Clinical Endocrinology & Metabolism. 105 (9): dgaa322. doi:10.1210/clinem/dgaa322. ISSN   0021-972X. PMC   7365695 . PMID   32491169.
  8. Russ G (Sep 2014). "Thyroid incidentalomas: epidemiology, risk stratification with ultrasound and workup". European Thyroid Journal. 3 (3): 154–63. 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, Jenny K.; Langer, Jill E.; Middleton, William D.; Wu, Carol C.; Hammers, Lynwood W.; Cronan, John J.; Tessler, Franklin N.; Grant, Edward G.; Berland, Lincoln L. (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. ISSN   1546-1440. PMID   25456025.
  10. Durante, Cosimo; Grani, Giorgio; Lamartina, Livia; Filetti, Sebastiano; Mandel, Susan J.; Cooper, David S. (2018-03-06). "The Diagnosis and Management of Thyroid Nodules: A Review". JAMA. 319 (9): 914–924. doi:10.1001/jama.2018.0898. ISSN   0098-7484. PMID   29509871. S2CID   5042725.
  11. 1 2 Wong KT, Ahuja AT (2005). "Ultrasound of thyroid cancer". Cancer Imaging. 5: 157–66. 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, Eleonora; Majlis, Sergio; Rossi, Ricardo; Franco, Carmen; Niedmann, Juan P.; Castro, Alex; Dominguez, Miguel (May 2009). "An Ultrasonogram Reporting System for Thyroid Nodules Stratifying Cancer Risk for Clinical Management". The Journal of Clinical Endocrinology & Metabolism. 94 (5): 1748–1751. doi: 10.1210/jc.2008-1724 . PMID   19276237.
  14. Grani, Giorgio; Lamartina, Livia; Ascoli, Valeria; Bosco, Daniela; Biffoni, Marco; Giacomelli, Laura; Maranghi, Marianna; Falcone, Rosa; Ramundo, Valeria; Cantisani, Vito; Filetti, Sebastiano; Durante, Cosimo (8 October 2018). "Reducing the number of unnecessary thyroid biopsies while improving diagnostic accuracy: towards the "right" TIRADS". The Journal of Clinical Endocrinology & Metabolism. 104 (1): 95–102. doi: 10.1210/jc.2018-01674 . PMID   30299457.
  15. Diaz Soto, Gonzalo; Halperin, Irene; Squarcia, Mattia; Lomena, Francisco; Puig Domingo, Manuel (10 September 2010). "Update in thyroid imaging. The expanding world of thyroid imaging and its translation to clinical practice" (PDF). Hormones. 9 (4): 287–298. doi:10.14310/horm.2002.1279. PMID   21112859. S2CID   15979225.
  16. Diana, S Dean; Hossein, Gharib. "Fine-Needle Aspiration Biopsy of the Thyroid Gland". Thyroid Disease Manager. Archived from the original on 12 July 2017. Retrieved 16 October 2017.
  17. 1 2 Renuka, I. V.; Saila Bala, G.; Aparna, C.; Kumari, Ramana; Sumalatha, K. (December 2012). "The Bethesda System for Reporting Thyroid Cytopathology: Interpretation and Guidelines in Surgical Treatment". Indian Journal of Otolaryngology and Head & Neck Surgery. 64 (4): 305–311. doi:10.1007/s12070-011-0289-4. PMC   3477437 . PMID   24294568.
  18. MedlinePlus Encyclopedia : Thyroid scan
  19. 1 2 Bin Saeedan, Mnahi; Aljohani, Ibtisam Musallam; Khushaim, Ayman Omar; Bukhari, Salwa Qasim; Elnaas, Salahudin Tayeb (2016). "Thyroid computed tomography imaging: pictorial review of variable pathologies". Insights into Imaging. 7 (4): 601–617. doi:10.1007/s13244-016-0506-5. ISSN   1869-4101. PMC   4956631 . PMID   27271508. Creative Commons Attribution 4.0 International License
  20. "UpToDate".
  21. Thyroid Nodule at eMedicine
  22. Schwartz 7th/e page 1679,1678
  23. 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.
  24. Grani, G; Calvanese, A; Carbotta, G; D'Alessandri, M; Nesca, A; Bianchini, M; Del Sordo, M; Fumarola, A (January 2013). "Intrinsic factors affecting adequacy of thyroid nodule fine-needle aspiration cytology". Clinical Endocrinology. 78 (1): 141–4. doi:10.1111/j.1365-2265.2012.04507.x. PMID   22812685. S2CID   205287747.
  25. Gates, Jeremy D.; Benavides, Linda C.; Shriver, Craig D.; Peoples, George E.; Stojadinovic, Alexander (2009). "Preoperative Thyroid Ultrasound In All Patients Undergoing Parathyroidectomy?". Journal of Surgical Research. 155 (2): 254–60. doi:10.1016/j.jss.2008.09.012. PMID   19482296.
  26. Robbins pathology 8ed page 767
  27. Tumino, D; Grani, G; Di Stefano, M; Di Mauro, M; Scutari, M; Rago, T; Fugazzola, L; Castagna, MG; Maino, F (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.
  28. "Echotherapy: Thyroid nodules".
  29. Vigneri, R; et al. (1993), "[Physiopathology of the autonomous thyroid nodule]", Minerva Endocrinol, 18 (4): 143–145, PMID   8190053.
Classification
D
External resources