Thyroid nodules are lesions caused by abnormal local growth of thyroid cells. The prevalence of thyroid nodules in the general population in the United States is estimated to be 3% to 7% by palpation and up to 20% to 76% by ultrasound. 2010, the Chinese Medical Association Endocrinology Branch published the results of a large community-based epidemiological survey of thyroid disease in China, with a prevalence of 18.6% in the 10 cities surveyed. Thyroid nodules are more common in the elderly, in women, in iodine deficient areas and in people with a history of radiation exposure.
Differentiate between benign and malignant and be aware of malignant risk factors
Thyroid nodules is a general name that can encompass a variety of thyroid disorders, such as nodular goiter, thyroid adenoma, thyroid cancer, thyroid lymphoma, and metastases.
Most patients with thyroid nodules are asymptomatic. Some larger nodules or malignant nodules may compress the trachea or invade local nerves, causing hoarseness and breathing difficulties. Most nodules are found accidentally during physical examinations or other tests of the neck. If a thyroid nodule is found, the first step is to find out what is causing it. The core of the evaluation of a thyroid nodule is to identify its benign or malignant nature, as this determines whether the patient needs surgical treatment. Detailed history taking and examination of the thyroid gland and cervical lymph nodes are important in the evaluation of thyroid nodules.
Factors predicting an increased risk of nodules being malignant
The presence of certain factors predicts an increased risk of malignant nodules, including: history of radiation therapy to the head and neck, family history of medullary thyroid cancer (MTC), papillary thyroid cancer (PTC) and multiple endocrine adenomatosis type 2 (MEN2), age <14 years or >70 years, male gender, hard, irregularly shaped, fixed and persistent nodules, dysphonia, dysphagia The nodules are hard, regular in shape, persistent hoarseness, dysphonia, dysphagia, etc.
Some patients with slowly progressive nodules (weeks or months) should be alerted to the possibility of malignancy; sudden onset of painful nodules should be noted for cystic nodule bleeding; progressive enlargement and painful thyroid nodules should be considered for undifferentiated thyroid cancer and thyroid lymphoma.
Several tools to evaluate thyroid nodules
To date, ultrasonography is the most sensitive test for evaluating thyroid nodules. All patients suspected of having a thyroid nodule or having an existing thyroid nodule need to have an ultrasound examination.
Currently, the primary means of evaluating thyroid nodules include the use of high-resolution ultrasound, measurement of thyroid function, and fine needle aspiration biopsy (FNAB) of thyroid nodules. Magnetic resonance imaging (MRI) and CT are not very helpful in determining the benignity or malignancy of the nodule. These tests are mainly used for preoperative assessment of the relationship between the nodule and the surrounding tissues, the presence or absence of airway compression and the extent of the thyroid gland behind the sternum.
Determination of thyroid function and autoantibodies
The literature reports that the prevalence of thyroid cancer correlates with serum thyrotropin (TSH) levels and that high-functioning nodules with suppressed TSH are less likely to be malignant. Thyroid autoantibody tests are mainly used to diagnose Hashimoto’s thyroiditis. Recently, it has been reported in the literature that an increased titer of thyroglobulin antibody (TgAb) significantly increases the risk of thyroid cancer, but no correlation has been found between thyroid peroxidase antibody (TPOAb) levels and the risk of thyroid cancer. Calcitonin measurements are valuable in the diagnosis of medullary thyroid carcinoma (MTC), mainly in patients with pre-surgical nodular goiter or a family history of MTC or MEN2.
Thyroid Nuclear Imaging
It is an imaging test that evaluates the functional status of the nodules, but is not necessary for the diagnosis of most thyroid nodules. In patients with low TSH levels or multinodular goiter, nuclide imaging can detect functional nodules or high-functioning adenomas. Functional thyroid nodules do not require further cytology in most cases because the likelihood of malignancy in these nodules is extremely low. However, in the same patient with an overall high-functioning multinodular goiter, there may be both functional nodules (hot nodules) and cold nodules (a small percentage of which may be malignant), which should be screened for.
Ultrasonography
Ultrasonography is useful not only to identify the nature of the nodule, but also to locate, puncture, treat and follow up on the thyroid nodule. The ultrasound report should include the shape, size, number of nodules, the state of the nodule margins, internal echogenic features, blood flow status and the condition of the lymph nodes in the neck.
Features of thyroid ultrasound that suggest malignant nodules include: hypoechoic nodules, microcalcifications, lack of peripheral halo, irregular nodule margins and disturbance of blood flow within the nodule, and nodules with aspect ratio >1 (height greater than width). The specificity of these features is high, >80%, but the sensitivity is low, 29%-77.5%. One feature alone is not sufficient to diagnose malignant lesions, but if >2 features are present at the same time or if one of the features is present in hypoechoic nodules, the sensitivity of the diagnosis of malignant disease can be increased to 87%-93%. This is the most reliable and valuable diagnostic method for identifying benign and malignant nodules.
Ultrasound examination of thyroid nodules is best performed by an experienced sonographer. In a meta-analysis including 41 studies with a total of 29,678 thyroid nodules, the authors analyzed the risk ratios (OR) of individual ultrasound and clinical features for predicting malignant thyroid nodules and found that the ORs were, in descending order, 10.15 for nodules with an aspect ratio >1, 7.14 for lack of halo sign, 6.76 for microcalcifications, 6.12 for irregular margins, 5.07 for hypoechoic, 4.69 for solid nodules 4.69, abundant blood flow in nodules 3.76, family history of thyroid cancer 2.29; nodules >4 cm in diameter 1.63, single nodule 1.43, history of head and neck irradiation 1.29.
In recent years, some studies have explored the use of acoustic palpation tissue imaging (VTI), ultrasound elastography, and ultrasonography (CEUS) for the differential diagnosis of benign and malignant thyroid nodules, which also have some value. However, the application of these techniques is still in a few studies, and no clinical consensus and uniform standards have been formed, pending systematic studies with expanded samples.
Puncture biopsy of thyroid nodules
Ultrasound-guided FNAB: FNAB is best performed under ultrasound guidance for those suspected of malignancy by thyroid ultrasonography. FNAB can be used to clarify the nature and cell type of nodules preoperatively, and its greatest value is to maximize the detection of patients with thyroid cancer for surgical treatment by this minimally invasive and simple method, and to avoid unnecessary surgery in numerous other patients with benign nodules.
Indications for FNAB.
(i) Solid hypoechoic nodules >10 mm in diameter, thyroid nodules of any size with suspected extraperitoneal growth or lymph node metastasis in the neck, and patients with a history of neck radiation exposure in childhood or adolescence.
②first-degree relatives of patients with PTC and MTC.
③Patients with a history of thyroid cancer surgery.
④ those with elevated serum calcitonin levels.
⑤ For nodules >10 mm, if ultrasonography reveals some signs associated with malignant lesions, such as hypoechoic and/or irregular borders, elongated nodules, microcalcifications or disturbance of blood flow signal in the nodules, FNAB biopsy should be performed in the presence of the above signs.
(6) In particular, the presence of ≥2 ultrasound suspicion criteria increases the risk of thyroid cancer.
For multinodular goiter, FNAB should be performed on nodes with malignant signs on ultrasound as described above. FNAB should be performed on the solid portion of mixed (cystic solid) thyroid nodules; the aspirated fluid specimen should also be examined cytologically; unexpected thyroid tumors detected by CT or MRI should be examined by ultrasound before performing ultrasound-guided FNAB; unexpected thyroid tumors detected by 18F-FDGPET-CT should be examined by both ultrasound and ultrasound-guided FNAB because of the higher risk of malignancy of such unexpected tumors.
Ultrasound-guided coarse needle aspiration biopsy (CNB): Since FANB examination takes less material and the judgment of cytological findings often needs to be done by experienced physicians, a significant proportion of fine needle aspiration cytological examination of the thyroid gland in clinical practice is still difficult to determine its benignity or malignancy. For patients with thyroid nodules whose cytologic findings are uncertain, ultrasound-guided CNB can be used when necessary and can provide additional diagnostic information.
Literature reports and our clinical practice confirm that CNB is a relatively safe and well-tolerated test, and because histological specimens are taken, it has a high diagnostic accuracy and is superior to FNAB, and can be used as a complementary diagnostic tool for thyroid nodules. However, CNB carries some risk of bleeding.
Several questions about the treatment of thyroid nodules
Do thyroid nodules require treatment?
Most patients with thyroid nodules do not require surgical treatment because most thyroid nodules are benign lesions, but 5% to 10% of these patients may have malignant nodules, which we call thyroid cancer or other malignant tumors, and these patients require prompt surgical treatment. For benign, large and symptomatic nodules with tracheal and local compression, surgical excision is feasible. For most asymptomatic benign nodules, regular ultrasound follow-up is sufficient.
Is levothyroxine (L-T4) treatment indicated?
L-T4 does not reduce the size of most thyroid nodules. In iodine-sufficient areas, 17-25% of solid thyroid nodules shrink after T4 suppression therapy (>50%). Because T4 suppression therapy can cause subclinical hyperthyroidism and patients treated are at increased risk of atrial fibrillation and reduced bone mineral density, T4 suppression therapy is not recommended routinely for most patients with nodular goiter and normal thyroid function. However, for some patients, such as young patients in iodine deficient areas, with a history of external exposure in childhood and growing nodular goiter, there may be some benefit to T4 therapy to achieve minimal suppression of TSH (e.g., <0.5 mU/L). If TSH is already below normal, suppressive therapy is not effective.
What are some common treatments?
Percutaneous alcohol injection or radiofrequency ablation may be used to treat benign cystic thyroid nodules. Radioactive iodine treatment may also be used for partial high-functioning nodules or toxic multinodular goiters diagnosed by nuclear imaging. For larger benign solid thyroid nodules laser, radiofrequency and microwave ablation treatments can be performed to shrink the nodules, but their long-term efficacy and safety are yet to be further investigated. In conclusion, thyroid nodules are a common clinical condition, and many tiny (<1 cm in diameter) thyroid nodules are detected, especially with the current use of thyroid ultrasound for routine checkups at many institutions. The vast majority of these nodules are benign and do not require specific treatment and should be followed up regularly. However, for nodules with suspicious malignant features on ultrasound, FNAB should be performed to clarify the diagnosis and, if necessary, surgical treatment.