I. Epidemiology of thyroid nodules
A thyroid nodule is an isolated lesion within the thyroid gland that can be palpated and/or distinguished from surrounding thyroid tissue by ultrasonography.
Thyroid nodules are the most common type of thyroid disorder. The prevalence varies depending on the screening method and the population enrolled. Physical examination and ultrasonography are currently the common screening methods, but the rate of nodule detection is influenced by the level and experience of the examiner. Epidemiological surveys have shown that the prevalence of palpation in iodine-sufficient areas is 5% in women and 1% in men. The highest prevalence of thyroid nodules was reported in the United States in a study that used high-definition ultrasound, and the detection rate of thyroid nodules was as high as 19-67% in a randomly selected population, with women and older adults being more common. There is a wide variation in the number of nodules reported as single over multiple, or multiple over single. The proportion of thyroid cancer in thyroid nodules varies, with most reports accounting for about 5%, but there is an increasing trend in recent years.
Etiology of thyroid nodules
The etiology of thyroid nodules is divided into two categories: benign and malignant. Benign thyroid nodules include: hyperplastic goiter (diffuse and nodular), toxic nodular goiter, thyroid adenoma, thyroid cyst, and focal thyroiditis. Malignant thyroid nodules include differentiated thyroid cancer (papillary thyroid cancer, follicular thyroid cancer), undifferentiated thyroid cancer, and medullary carcinoma.
Presentation of thyroid nodules
Thyroid nodules are independent lesions in the thyroid gland, which can be single or multiple. Some of them can be seen on visual inspection and palpated on palpation, and they can be detected on ultrasound as distinct from the surrounding tissues; other non-palpable thyroid nodules are detected on ultrasound or other imaging tests that can show the anatomical structure. However, thyroid nodules that are not confirmed by ultrasound are not diagnosed as thyroid nodules even if they can be palpated.
An unpalpable nodule has the same probability of malignancy as a palpable nodule of the same size.
Evaluation and management of thyroid nodules
1. Categories of thyroid nodules that need to be evaluated Benign lesions account for about 95% of thyroid nodules and malignant lesions account for only about 5% (91% of which are differentiated thyroid cancer, 5% are medullary thyroid carcinoma, and only 3% are undifferentiated thyroid cancer). The current consensus is to evaluate and manage thyroid nodules >1 cm in diameter and nodules <1 cm in diameter, but with suspicious signs of cancer on ultrasound, history of head and neck radiation exposure, and positive family history of thyroid cancer. Those with simple thyroid nodules <1cm only need ultrasound review for follow-up.
2. Clinical evaluation of thyroid nodules
History and physical examination are the most basic steps to assess the nature of thyroid nodules. Proper evaluation requires a detailed and complete history taking and careful physical examination of the thyroid and adjacent lymph nodes. The literature reports that more than 60% of thyroid cancers can be diagnosed by physical examination by an experienced physician.
Factors that suggest a high likelihood of malignant thyroid nodules by history and physical findings are.
(i) Having a palpable thyroid nodule at age <20 years or >70 years;
② History of head, neck or body radiation exposure (radiation therapy for tumor or bone marrow transplantation);
③First-degree relative with thyroid cancer;
④ Rapid growth of nodules;
⑤ hoarseness of voice;
(6) Vocal cord paralysis;
(7) Enlarged and fixed lymph nodes in the neck ipsilateral to the nodule. Further evaluation and management are required.
3. Laboratory evaluation of thyroid nodules
If the nodule is >1-1.5 cm in diameter, serum TSH should be measured and the TSH is low, suggesting that the nodule may be secreting thyroid hormones. The elevated TSH indicates hypothyroidism and requires further measurement of thyroid autoantibodies or FNA.
3.2 Evaluation of serum thyroglobulin (Tg) serum Tg is elevated in most thyroid diseases and lacks specificity and sensitivity in the diagnosis of thyroid cancer.
3.3 Evaluation of serum calcitonin assay Serum calcitonin is useful for early detection of parathyroid cell hyperplasia and medullary thyroid carcinoma. A blood calcitonin >100 pg/mL without stimulation suggests the possibility of medullary thyroid carcinoma.
4. Assessment of thyroid nodules by ancillary tests
4.1 Evaluation of thyroid nucleus scan Previously, thyroid nucleus imaging was the most commonly used method to assess the nature of thyroid nodules. Radionuclides (131I, 125I, 99mTc) are used for dynamic or static imaging of the thyroid gland to reflect the location, size, morphology and function of the thyroid gland and its nodules. Thyroid nodules are classified as “hot nodules”, “warm nodules” and “cold nodules” depending on the amount of nuclide taken up by the nodules. Because most benign nodules, like thyroid cancer, take up less nuclide, they are called “cold nodules” and therefore have little diagnostic value. Therefore, thyroid nuclide imaging has diagnostic value only for about 10% of hot nodules (autonomous high-functioning thyroid adenomas), while the diagnosis of the remaining 90% of nodules is still uncertain.
4.2 Ultrasonographic evaluation of the thyroid gland Ultrasonography of the thyroid gland is necessary to confirm the diagnosis of thyroid nodules, i.e., to determine the size and number of nodules and to show the presence or absence of cystic and cancerous signs. Its accuracy depends on the skill and experience of the examiner. Cancerous signs include microcalcifications, hypoechogenicity of solid nodules, and abundant blood supply in the nodules. It is generally accepted that anechoic lesions and homogeneous hyperechoic lesions have a low risk of cancer. However, the results of the study show that it is not yet possible to distinguish well between benign and malignant lesions based on ultrasound findings.
4.3 FNA evaluation Fine needle aspiration cytology (FNA) of the thyroid gland is the most accurate and cost-effective method for evaluating thyroid nodules. FNA biopsy results are divided into four categories.
① malignant nodules;
②Suspected malignant nodules;
③ Benign nodules;
(iv) unsatisfactory specimen sampling. In the latter case, repeat puncture under ultrasound guidance is required.
5. Evaluation of multiple thyroid nodules The risk of malignancy is the same as for isolated nodules. If there are more than 2 nodules >1-1.5 cm in diameter, FNA is performed on nodules with suspicious cancer signs on ultrasound; if there are more than 2 nodules >1-1.5 cm in diameter without suspicious cancer signs on ultrasound, FNA is performed on the largest nodule; TSH is below the normal range, thyroid nuclear imaging is performed first to assess the functional status of each nodule >1-1.5 cm, of which If the nodule is “cold” or “warm”, FNA should be performed especially if there are suspicious signs of cancer on ultrasound.
In summary, the following conditions suggest the need for surgery.
①FNA of malignant nodes;
②solid nodes with unsatisfactory FNA repeatedly;
(iii) FNAC suspected malignant nodes;
④Some nodules, especially those with cystic changes, are always unsatisfactory for FNAC specimens;
⑤Nodules with diameter >2cm and hard.
The current consensus is to perform total or near-total thyroidectomy, and to remove the residual thyroid tissue with radioactive iodine and thyroid hormone suppression therapy after surgery.
V. Follow-up and treatment of benign thyroid nodules
If the nodule increases in size, repeat FNA, especially ultrasound-guided FNA, and decide on the treatment according to the results.
2. Treatment The effect of thyroxine on benign thyroid nodules: in areas with low iodine intake, benign nodules may shrink when levothyroxine (L-T4) is taken and TSH is suppressed; in areas with adequate iodine supply, the above effect is not seen. Unanimous opinion does not recommend the routine use of thyroxine suppression therapy for benign thyroid nodules.
Management of thyroid nodules in children
Thyroid nodules in children are less common than in adults and have a malignancy rate equal to or higher than that of adults. The assessment and treatment methods are the same as for adults (clinical assessment, laboratory assessment, assessment of ancillary tests, etc.).
VII. Management of thyroid nodules in pregnancy
The evaluation of thyroid nodules in pregnancy is the same as in non-pregnant women, except that thyroid nucleus imaging cannot be performed. If thyroid nodules are normal or hypothyroid with thyroid nodules, FNA should be performed; if TSH levels are still suppressed in early pregnancy, ultrasonography and FNA should be performed after delivery; if malignant nodules are found in early pregnancy, ultrasound monitoring and nodules grow, surgery in mid-pregnancy is an option; if nodules are stable in size by mid-pregnancy, or if malignant nodules are found in late pregnancy, surgery after delivery is an option.
Conclusion: The prevalence of thyroid nodules is high, but the proportion of malignancy is small and the degree of malignancy is low; most thyroid nodules regress well naturally; there are reliable and easy methods to identify benign and malignant thyroid nodules; intervention methods and effects of thyroid nodules are limited; the current expert consensus on thyroid nodules does not require active intervention is unanimous. For most patients, close clinical observation and follow-up may be the most appropriate management.