Etiology, diagnosis, and treatment of thyroid nodules.
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 in different tests, such as thyroid nodules detected by palpation as a mass within the thyroid region; thyroid nodules detected by thyroid ultrasonography as an area of focal echogenic abnormality. 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 found on palpation is 3%-7% in the general population, while the prevalence of thyroid nodules found on high definition ultrasound is 30%-60%. Most thyroid nodules are benign, and malignant nodules account for only about 5-10% of thyroid nodules. The key to the diagnosis and treatment of thyroid nodules is to identify benign and malignant.
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 synthesis enzymes, 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.
Cysts: nodular goiter, degenerative adenoma and old hemorrhage with cystic changes, cystic thyroid cancer, congenital thyroglossal cysts and cysts caused by the 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 carcinoma or MEN2 type; (3) age less than 20 years or more than 70 years; (4) male; (5) nodules growing rapidly and more than 2 cm in diameter; (6) with persistent hoarseness, dysphonia, dysphagia and dyspnea; (7) nodules with hard texture, (7) hard, irregular and fixed nodes; (8) enlarged lymph nodes in the neck.
Laboratory and ancillary tests
1. Serum thyrotropin (TSH) and thyroid hormone: All patients with thyroid nodules should have their serum 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.
The majority 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% 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: Significantly elevated serum calcitonin level indicates medullary carcinoma of thyroid nodules. Those with family history of medullary thyroid cancer or multiple endocrine adenomatosis should have their serum calcitonin levels measured in the basal or stimulated state.
5.Thyroid ultrasonography: High definition thyroid ultrasonography is the most sensitive method to evaluate thyroid nodules. It can be used not only to discriminate the nature of nodules, 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 in nodules are: (l) microcalcifications; (2) irregular nodule margins; (3) disturbance of blood flow in nodules; all three have high specificity suggestive of malignant lesions, reaching more than 80%, but lower sensitivity, 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 current studies show that the benignity or malignancy of nodules is 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.Thyroid nuclide imaging: Thyroid nuclide imaging is characterized by the ability to evaluate the function of nodules. 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 present 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 for assessing the relationship between thyroid nodules and surrounding tissues, especially for detecting retrosternal goiter.
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. Treatment of malignant thyroid nodules: Most malignant tumors of the thyroid need to be treated with surgery. 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: Most patients with benign thyroid nodules do not need treatment, but should be followed up every 6-12 months. If necessary, thyroid ultrasonography and repeat thyroid FNAC examination may be performed. A small number of patients require treatment. The current treatment options are as follows.
(1) Left thyroxine (L-T4) suppression therapy: The purpose of L-T4 therapy is to shrink existing nodules; however, studies have found that only 20% of thyroid nodules shrink in L-T4-treated patients compared to before, and it has also been found that shrunken thyroid nodules can become larger again after stopping the drug. Also, because long-term L-T4 treatment can lead to a variety of adverse effects, such as a significant decrease in bone mineral density in postmenopausal women and a significantly increased risk of atrial fibrillation. Therefore, L-T4 therapy is currently considered to be suitable for only a small number of patients with benign thyroid nodules and is not recommended for widespread use, especially not for male patients with serum TSH levels <1.0 mIU/L, age >60 years, postmenopausal women and patients with combined cardiovascular disease. If the thyroid nodules do not shrink after 3-6 months of L-T4 treatment, or if the nodules increase in size instead, a new FNAC examination is required.
(2) Surgery: If a patient with thyroid nodules has local pressure symptoms or hyperthyroidism, or if the nodules are progressively enlarging or the FNAC examination suggests suspicion of cancer, surgical treatment is feasible. Do not operate whenever there are nodules. In fact, many patients do not need surgery. Clinical observation is completely possible. Observe the changes. Check every 6 months or a year to see if there is any change.
(3) Ultrasound-guided percutaneous alcohol injection (PEI) treatment: PEI is a minimally invasive method of treating thyroid nodules. It is mainly used to treat thyroid cysts or nodules combined with cystic changes. This method has a high recurrence rate. Large or multiple cysts may require multiple treatments to achieve better results. It is not recommended for solitary, solid nodules. Special care should be taken to make sure that FNAC is done before PEI treatment to exclude the possibility of malignant changes before implementation.
(4) Radioactive l3lI therapy: The purpose of radioactive l3lI therapy is to remove functionally autonomous nodules and restore normal thyroid function status, with an effectiveness of 80% to 90%. A small number of faithful patients can develop hypothyroidism after treatment, and very few patients develop Graves’ disease after treatment. l3lI treatment is used for those with autonomic high-functioning adenoma, toxic nodular goiter with thyroid volume less than l00ml or those who are not suitable for surgical treatment or recurrence of surgical treatment. This method is not suitable for patients with large thyroid nodules and is contraindicated in pregnant and lactating women.
3. Treatment of suspected malignant and undiagnosed thyroid nodules: If the diagnosis of cystic or solid thyroid nodules is not clear by FNAC examination, the FNAC examination should be repeated so that the diagnosis is clear in 30% to 50% of patients. If the diagnosis cannot be confirmed by repeated FNAC examination, especially if the nodule is large and fixed, surgery is required.
The treatment of thyroid nodules in children and pregnancy: thyroid nodules found during pregnancy are treated the same as those found during non-pregnancy; however, thyroid nuclear imaging and radioactive 131I therapy are prohibited during pregnancy. fnac testing can be performed during pregnancy or postponed to the postpartum period. If the nodule is malignant, it is safer to perform the procedure in the third to sixth month of pregnancy; otherwise, it should be performed at an elective date after delivery.
Thyroid nodules in children are relatively rare and have a higher malignancy rate than adults, with cancer accounting for l5 %. Therefore, FNAC should also be performed on pediatric patients with thyroid nodules. When cytological examination suggests that the nodule is a malignant lesion or a suspected malignant lesion, surgical treatment should be performed.
5. A new method developed in recent years: radiofrequency ablation is also a good choice. It avoids the risk of trauma of surgical incision. Of course it must be a benign nodule to be allowed.
Finally, special attention:; patients in plain areas with thyroid nodules, except for pregnant women and children and adolescents, try to eat less iodized salt. This is because there is no lack of iodine in our normal life. Too little and too much iodine can cause the formation of thyroid nodules. There is non-iodized salt in the market.