Thyroid nodules are scattered lesions caused by abnormal localized growth of thyroid cells. A “nodule” that is palpable but not confirmed on ultrasonography cannot be diagnosed as a thyroid nodule. Nodules that are not palpable on physical examination but are found incidentally on imaging are called “accidental thyroid nodules”.
The detection rate of thyroid nodules is influenced by the method of examination. The detection rate by palpation in the general population is 3-7%, while the prevalence of thyroid nodules detected by high-resolution thyroid B-mode ultrasonography is as high as 20%-70%. The majority of thyroid nodules are benign and the proportion of malignant lesions is very small, accounting for only about 5% of them.
There are various causes of thyroid nodules, which can be divided into two categories: benign and malignant.
1. Hyperplastic nodular goiter
Various causes, including high or low iodine, consumption of goiter-causing substances, consumption of goiter-causing drugs or defects in thyroxine synthetase, lead to the proliferation of thyroid follicular epithelial cells and nodule formation.
2. Neoplastic nodules
Benign thyroid adenoma, papillary thyroid carcinoma, follicular cell carcinoma, Hürthle cell carcinoma, medullary thyroid carcinoma, undifferentiated carcinoma, lymphoma, and other malignant tumors of follicular and non-follicular cells of the thyroid gland, as well as metastatic carcinoma.
3.Cysts
Nodular goiter, degenerative adenoma and old hemorrhage lead to cyst formation. Some thyroid cancers, especially papillary carcinoma, may also develop cystic changes. A few cysts are caused by congenital thyroglossal cysts and remnants of the fourth gill slit.
4.Inflammatory nodules
Acute septic thyroiditis, subacute thyroiditis, and chronic lymphocytic thyroiditis can all appear in the form of nodules. In rare cases, thyroid nodules are due to tuberculosis or syphilis.
The histopathological changes in simple goiter are mainly proliferative degenerative changes of the tissue. It is caused by overproduction of thyrotropic hormone (TSH) stimulating the thyroid tissue due to feedback from thyroid hormone deficiency (iodine deficiency and other factors) and is a compensatory effect. This hyperplasia does not necessarily diffuse to all of the thyroid gland, but is often limited to a portion of it, and this change can restore normal tissue morphology if treated promptly. The reason for partial regional hyperplasia may be that different areas of the thyroid tissue are not equally sensitive to TSH.
If the lesion continues to develop without timely treatment, colloid accumulates in the follicular lumen, follicular epithelial cells become deformed, and a series of pathological changes occur in the tissue cells such as degeneration, necrosis, calcification, fibrosis and cystic degeneration, eventually forming colloid nodules, also called nodules, which are often palpable lumps in the thyroid gland. Once they become such colloid nodules, it is impossible to restore the original tissue morphology, and the surrounding cells continue to be destroyed, and the nodules The nodules continue to grow in size, and small nodules continue to form in the rest of the body, resulting in nodules of different sizes in the thyroid gland. The nodules continue to increase in size and size, resulting in a variety of compression symptoms on the surrounding organs and complex clinical symptoms.
Ancillary tests.
Priority tests
Serum thyrotropic hormone (TSH) and thyroid hormone
All patients with thyroid nodules should have their serum line serum TSH and thyroid hormone levels tested. Studies have shown that patients with thyroid nodules with lower than normal TSH levels have a lower percentage of nodules that are malignant than those with normal or elevated TSH levels. That is, the vast majority of patients with thyroid malignancy have normal thyroid function. If the serum TSH is low and the thyroid hormone is high, it suggests a high-functioning nodule. The majority of these nodules are benign.
Thyroid autoantibodies
Serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels are among the gold indicators for detecting Hashimoto’s thyroiditis, especially if serum TSH levels are elevated.
Over 85% of patients with Hashimoto’s thyroiditis have elevated serum anti-thyroid antibody levels; however, a small number of patients with Hashimoto’s thyroiditis may have a combination of papillary thyroid cancer or thyroid lymphoma.
Ultrasonography of the thyroid gland
Ultrasound of the neck should be performed in all patients with thyroid nodules. High-resolution thyroid ultrasound is the most sensitive method for evaluating thyroid nodules. It can be used not only to identify the nature of the nodule, but also for ultrasound-guided fine needle aspiration and cytology (FNAC) of the thyroid gland.
The report should include the location, morphology, size, number of nodules, status of nodule margins, internal structure, echogenic form, blood flow status and cervical lymph nodes. Ultrasonography can assist in identifying benign and malignant thyroid nodules, and the ability to do so is related to the clinical experience of the sonographer.
Almost all thyroid nodules with the following two types of ultrasound changes are benign.
(i) purely cystic nodules;
②Nodules with multiple small vesicles occupying more than 50% of the nodule volume and with spongy changes are 99.7% benign.
In contrast, the following ultrasound signs suggest a high probability of thyroid cancer.
①Solid hypoechoic nodules;
(2) Abundant blood supply in the nodule (in case of normal TSH);
(3) Irregular nodule shape and margin, halo absence;
④Microcalcifications, pinpoint-like diffuse distribution or clusters of calcifications;
(⑤Consistent with abnormal ultrasound images of cervical lymph nodes, such as rounded lymph nodes, irregular or blurred borders, uneven internal echogenicity, internal calcification, poorly demarcated dermatomedullary, disappearance of lymphatic portals or cystic changes.
It is worth noting that the current findings show that the benignity or malignancy of nodes is not related to the size of the nodes, and malignancy is not uncommon in nodes less than 1.0 cm in diameter; it is not related to whether the nodes are palpable; it is not related to whether the nodes are solitary or multiple; and it is not related to whether the nodes are combined with cystic changes.
Optional tests
Thyroglobulin (Tg) levels
Thyroglobulin (Tg) is a specific protein produced by the thyroid gland and is secreted by the thyroid follicular epithelium. A variety of thyroid disorders can cause elevated serum Tg levels, including DTC, goiter, inflammation or damage to thyroid tissue, and hyperthyroidism (overactive thyroid). Serum Tg is not helpful in identifying benign or malignant thyroid nodules.
Serum calcitonin level
Those with a family history of medullary thyroid cancer or multiple endocrine adenomatosis should have their serum calcitonin levels measured in the basal or stimulated state. A significantly elevated serum calcitonin level suggests a medullary thyroid nodule.
MRI and CT examinations
CT and MRI are not superior to ultrasound in assessing the benignity or malignancy of thyroid nodules.
For thyroid nodules to be treated surgically, preoperative CT or MRI of the neck is feasible to show the relationship between the nodule and the surrounding anatomical structures and to look for suspicious lymph nodes to assist in the development of the surgical plan. In order not to interfere with possible postoperative I131 imaging and I131 therapy, iodine-containing contrast agents should be avoided in CT examinations.
CT, MRI and 18F-FDG PET are not recommended as routine tests for the evaluation of thyroid nodules.
Thyroid nuclide imaging
Due to the resolution of the imaging instrument, thyroxine imaging is indicated for the evaluation of thyroid nodules >1 cm in diameter. In single (or multiple) nodules with decreased serum TSH, thyroid 131I or 99mTc nuclide imaging can determine whether a nodule (or nodules) has autonomic uptake (“hot nodules”). The vast majority of “hot nodules” are benign and generally do not require fine needle aspiration biopsy (FNAB).
Thyroid nodules >1 cm in diameter with decreased serum TSH should be imaged with thyroid I131 or 99mTc to determine if the nodule has autonomic uptake.
Fine needle aspiration biopsy (FNAB)
FNAB is the most sensitive and specific method for preoperative assessment of benign and malignant thyroid nodules. Ultrasound-guided FNAB can improve the success rate of retrieval and diagnostic accuracy.
The sensitivity of preoperative diagnosis of thyroid cancer by FNAB is 83% (65-98%), the specificity is 92% (72-100%), the positive prediction rate is 75% (50-96%), the false negative rate is 5% (1-11%), and the false positive rate is 5% (0-7%). fnab cannot distinguish follicular carcinoma from follicular cell adenoma of the thyroid. Therefore, preoperative FNAB can help reduce unnecessary thyroid nodule surgery and help determine the appropriate surgical plan.
FNAB can be considered for any thyroid nodule >1 cm in diameter. However, FNAB is not routinely performed in the following cases.
(1) “hot nodules” with autonomic uptake as confirmed by thyroid nuclide imaging;
②Ultrasound suggests a purely cystic nodule;
(3) nodules that are highly suspicious of malignancy based on ultrasound images.
FNAB is not recommended for thyroid nodules <1 cm in diameter, but ultrasound-guided FNAB may be considered in the following cases.
①Ultrasound suggests a nodule with malignant signs;
(ii) Abnormal ultrasound images of the lymph nodes in the neck;
③History of radiation exposure to the neck or radiation contamination during childhood;
④History or family history of thyroid cancer or thyroid cancer syndrome;
⑤ Positive PET image of 18F-FDG;
(6) Abnormally elevated serum Ct level.
Compared with palpated FNAB, ultrasound-guided FNAB has a higher success rate of sampling and diagnostic accuracy. To improve the accuracy of FNAB, the following methods can be used: repeated puncture sampling at multiple sites of the same nodule; sampling at sites where ultrasound suggests suspicious signs; sampling at solid sites of cystic nodules with concurrent cyst fluid cytology. In addition, experienced operators and cytopathological diagnostic physicians are also important aspects to ensure the success rate and diagnostic accuracy of FNAB.
According to international standards and domestic reports, the following classification is recommended in determining FNAB results.
Thyroid cancer molecular marker detection
Prospective studies have confirmed that the detection of certain molecular markers of thyroid cancer, such as BRAF mutation, Ras mutation, RET/PTC rearrangement, etc., in puncture specimens can improve the diagnosis rate for thyroid nodules that cannot be determined as benign or malignant by FNAB. The detection of BRAF mutation status in preoperative puncture specimens can also help in the diagnosis and clinical prognosis of papillary thyroid cancer (PTC) and facilitate the development of individualized diagnosis and treatment plans.
Treatment.
Most benign thyroid nodules require only regular follow-up and no specific treatment. In rare cases, surgery, TSH suppression, radioiodine (RAI) therapy, or other treatment options are available.