I. Overview
A thyroid nodule is a mass or masses of abnormal tissue structure in the thyroid gland due to various causes. Thyroid nodules may appear differently on different tests, for example, thyroid nodules detected by palpation are masses found in the thyroid region; thyroid nodules detected by ultrasonography are areas of focal echogenic abnormalities. The results of the two tests are sometimes inconsistent, such as when a thyroid mass is detected on physical examination but no nodule is found on thyroid ultrasonography, or when a thyroid nodule is not palpated on physical examination but is found on thyroid ultrasonography.
Thyroid nodules are very common. The prevalence of thyroid nodules in the general population is 3%-7% on palpation, while the prevalence of thyroid nodules on high definition ultrasound is 20%-70%. Most thyroid nodules are benign, and malignant nodules account for only about 5% of thyroid nodules. The key to the diagnosis and treatment of thyroid nodules is to distinguish between benign and malignant nodules.
Classification and etiology
1. Hyperplastic nodular goiter:
High or low iodine intake, consumption of goiter-causing substances, consumption of goiter-causing drugs or defective thyroid hormone synthetase, etc.
2. Neoplastic nodules:
Benign thyroid adenoma, papillary thyroid carcinoma, follicular cell carcinoma, Hurthle cell carcinoma, medullary thyroid carcinoma, undifferentiated carcinoma, lymphoma, and other follicular cell and non-follicular cell malignancies of the thyroid gland, as well as metastatic carcinoma.
3.Cysts:
Nodular goiter, degenerative adenoma and old hemorrhage with cystic changes, cystic thyroid cancer, congenital thyroglossal cysts and cysts due to remnants of the fourth gill slit.
4. Inflammatory nodules:
Acute suppurative 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.
Clinical manifestations
The vast majority of patients with thyroid nodules have no clinical symptoms and are often detected by physical examination or by their own touch or imaging. When the nodules compress the surrounding tissues, corresponding clinical manifestations may appear, such as hoarseness, breath-holding, and difficulty in swallowing. When combined with hyperthyroidism (hyperthyroidism), corresponding clinical manifestations of hyperthyroidism, such as palpitations, excessive sweating, and hand tremors, may occur.
A detailed history taking and a thorough physical examination are important to assess the nature of the thyroid nodule. The main points of history taking are the patient’s age, gender, history of head and neck radiotherapy, size and rate of change and growth of nodules, presence of local symptoms, presence of hyperthyroidism and hypothyroidism (hypothyroidism), presence of thyroid tumors, medullary thyroid carcinoma or multiple endocrine adenomatosis type 2 (MEN2), familial polyposis, Cowden’s disease and Gardner syndrome, and other familial history of disease. Physical examination will focus on the number, size, texture, mobility, presence of pressure pain, and presence of enlarged lymph nodes in the neck of the nodule.
Clinical evidence suggestive of malignant thyroid nodules include:
(1) History of treatment with neck radiography;
(2) Family history of medullary thyroid cancer or MEN2 type;
(3) Age less than 20 years or more than 70 years;
(4) Male ;
(5) Rapidly growing nodules with a diameter of more than 2 cm;
(6) persistent hoarseness, dysphonia, dysphagia and dyspnea;
(7)The nodules are hard, irregular and fixed in shape;
(8) With enlarged lymph nodes in the neck.
Laboratory and auxiliary tests
1. Serum thyrotropin (TSH) and thyroid hormone:
All patients with thyroid nodules should have their TSH and thyroid hormone levels measured. The majority of patients with thyroid malignancy have normal thyroid function. If serum TsH is low and thyroid hormone is high, this is a sign of a high functioning nodule. Most of these nodules are benign.
2. Thyroid autoantibodies:
Serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels are one of the gold indicators for detecting Hashimoto’s thyroiditis, especially if serum TSH levels are elevated. 85% or more of patients with Hashimoto’s thyroiditis have elevated serum anti-thyroid antibody levels. However, a few patients with Hashimoto’s thyroiditis can be combined with papillary thyroid cancer or thyroid lymphoma.
3. Measurement of thyroglobulin (Tg) levels:
Serum Tg is not helpful in identifying the nature of the nodule.
4.Measurement of serum calcitonin level:
A significantly elevated serum calcitonin level indicates a medullary thyroid nodule. Those with family history of medullary thyroid carcinoma or multiple endocrine adenomatosis should have their serum calcitonin levels measured in the basal or stimulated state.
5.Ultrasound examination of thyroid gland:
High-resolution thyroid ultrasonography 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.
Features suggestive of malignant lesions of nodules are:
(1) microcalcifications;
(2) Irregular nodule margins;
(3) disturbance of blood flow in the nodule.
The specificity of the three features suggesting malignant lesions is high, both reaching more than 80%, but the sensitivity is low, ranging from 29% to 77.5%. Therefore, one feature alone is not sufficient to diagnose malignant lesions. However, if two or more features are present at the same time, or if one of these features is combined in a hypoechoic nodule, the sensitivity of the diagnosis of malignant lesions increases to 87%-93%. Invasion of the hypoechoic nodule into the outer thyroid envelope or the muscles surrounding the thyroid gland or enlargement of the cervical lymph nodes with loss of lymph node portal structures, cystic changes, or microcalcifications in the lymph nodes and disturbance of the blood flow signal suggest a malignant nodule. It is worth noting that the results of the current study show that the benignity and malignancy of nodules are not related to the size of the nodules, and malignancy is not uncommon in nodules less than 1 cm in diameter; it is not related to whether the nodules are palpable or not; it is not related to whether the nodules are single or multiple; and it is not related to whether the nodules are combined with cystic changes.
6.Thyroxine imaging:
Thyroid nuclide imaging is characterized by the ability to evaluate the function of the nodule. The nodules are classified as “hot nodules”, “warm nodules” and “cold nodules” according to their ability to take up radionuclides.” Hot nodules” account for 10% of the nodules and “cold nodules” account for 80% of the nodules. It is important to note that when a nodule is cystic or a thyroid cyst is detected on thyroid nuclide imaging, it also appears as a “cold nodule”. In this case, a combination of thyroid ultrasound can help in the diagnosis. Hot nodules” are 99% benign and malignant are extremely rare. Cold nodules” are malignant in 5-8% of cases. Therefore, if the thyroid nuclei are “hot nodules”, they can be judged as benign. It is not very helpful to determine the benignity or malignancy of thyroid nodules by “cold nodules”.
7. Magnetic resonance imaging (MRI) and computed tomography (CT) examinations:
MRI or CT is not as sensitive as thyroid ultrasonography to help detect thyroid nodules and determine the nature of the nodules, and is expensive. Therefore, it is not recommended for routine use. However, it has diagnostic value in assessing the relationship between thyroid nodules and surrounding tissues, especially in the detection of retrosternal goiter.
8. FNAC examination:
FNAC examination is the most reliable and valuable diagnostic method to identify benign and malignant nodules. The literature reports that its sensitivity is 83%, specificity is 92%, and accuracy is 95%. FNAC should be performed in all cases where malignant nodules are suspected. The preoperative FNAC test helps to identify the cytological type of cancer before surgery and determine the correct surgical plan. It should be noted that FNAC test cannot differentiate follicular carcinoma and follicular cell adenoma of thyroid.
V. Treatment
1. Management of malignant thyroid nodules:
Most malignant tumors of the thyroid need to be treated surgically. Undifferentiated thyroid cancer is highly malignant and has distant metastases at the time of diagnosis, so it is difficult to achieve the therapeutic goal with surgery alone. Thyroid lymphoma is sensitive to chemotherapy and radiotherapy, so once diagnosed, chemotherapy or radiotherapy should be used.
2. Treatment of benign nodules:
The majority of patients with benign thyroid nodules do not require treatment, but need to be followed up every 6 to 12 months. If necessary, thyroid ultrasonography and repeat thyroid FNAC may be performed. A small number of patients require treatment.