Question 1: Definition of thyroid nodules
A thyroid nodule is a scattered lesion 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”.
Question 2: Prevalence of thyroid nodules
Thyroid nodules are very common. The detection rate by palpation in the general population is 3-7%, while the detection rate with the help of high-resolution ultrasound can be as high as 20-76%.
Question 3: Key points in the evaluation of thyroid nodules
5-15% of thyroid nodules are malignant, i.e. thyroid cancer. The clinical management of benign and malignant thyroid nodules varies significantly in terms of their impact on the quality of life (QOL) of patients and the medical costs involved. Therefore, the key point in the evaluation of thyroid nodules is the differentiation between benign and malignant.
Question 4: Clinical presentation of thyroid nodules
Most patients with thyroid nodules have no clinical symptoms. When combined with abnormal thyroid function, corresponding clinical manifestations may occur. Some patients have symptoms of compression such as tearing of the voice, feeling of pressure, and difficulty in breathing/swallowing due to nodule compression of surrounding tissues.
The following medical history and physical examination findings are risk factors for thyroid cancer.
①History of childhood head and neck radiation exposure or exposure to radioactive fallout.
②History of systemic radiation therapy.
(3) History of differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) or multiple endocrine adenomatosis type 2 (MEN2), familial polyposis, certain thyroid cancer syndromes (e.g., Cowden syndrome, Carney syndrome, Werner syndrome), and thyroid cancer syndrome. Carney syndrome, Werner syndrome, and Gardner syndrome, etc.) prior or family history.
④Male.
⑤ Rapid nodule growth.
(6) Persistent voice tearing and dysphonia, with exclusion of vocal fold pathology (inflammation, polyps, etc.).
(7) Difficulty in swallowing or breathing.
(8) Irregularly shaped nodules with fixed adhesions to surrounding tissues.
(9) Pathological enlargement of lymph nodes in the neck.
Question 5: Laboratory tests for thyroid nodules
All patients with thyroid nodules should have their serum thyroid stimulating hormone (TSH) levels tested. Studies have shown that patients with thyroid nodules with lower than normal TSH levels have a lower percentage of malignant nodules than those with normal or elevated TSH levels.
Thyroglobulin (Tg) is a specific protein produced by the thyroid gland and secreted by the thyroid follicular epithelium. A variety of thyroid disorders can cause elevated serum Tg levels, including differentiated thyroid cancer, goiter, inflammation or damage to thyroid tissue, and hyperthyroidism (hyperthyroidism), etc. Therefore, serum Tg cannot identify benign or malignant thyroid nodules.
Question 6: Ultrasonography
High-resolution ultrasonography is the method of choice for the evaluation of thyroid nodules. Ultrasound of the neck should be performed for any “thyroid nodule” suspected by palpation and suggested by examination. Neck ultrasound can confirm the presence of a “thyroid nodule” and determine the size, number, location, texture (solid or cystic), shape, border, envelope, calcification, blood supply and relationship to surrounding tissues, as well as the presence and size, morphology and structural characteristics of lymph nodes in the neck region.
Certain ultrasound signs can help in the differentiation of benign and malignant thyroid nodules. Almost all of the thyroid nodules with the following two types of ultrasound changes are benign:
(i) purely cystic nodules.
(2) Nodules with multiple small vesicles occupying more than 50% of the nodule volume and with spongy changes are 99.7% benign.
The following ultrasound signs suggest a high probability of thyroid cancer.
① solid hypoechoic nodules.
② abundant blood supply in the nodule (in case of normal TSH).
(3) Irregular nodule shape and margin, halo absence.
④miniature calcifications, pinpoint-like diffuse distribution or clustered distribution of calcifications.
⑤ Concomitant abnormal ultrasound images of cervical lymph nodes, such as rounded lymph nodes, irregular or blurred borders, uneven internal echogenicity, calcification inside, poorly demarcated skin medulla, disappearance of lymph gates or cystic changes. The ability to identify benign and malignant thyroid nodules by ultrasonography is related to the clinical experience of the ultrasonographer.
Question 7: The role of thyroxine imaging in the evaluation of thyroid nodules
Due to the resolution of the imaging instrument, thyroxine imaging is suitable 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 autoreceptor function “hot nodules”. The vast majority of “hot nodules” are benign and usually do not require fine needle aspiration biopsy (FNAB).
Question 8: The role of fine needle aspiration biopsy (FNAB) in the evaluation of thyroid nodules
FNAB has a sensitivity of 83% (65-98%), a specificity of 92% (72-100%), a positive predictive rate of 75% (50-96%), a false negative rate of 5% (1-11%), and a false positive rate of 5% (0-7%) in the preoperative diagnosis of thyroid cancer. 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 confirmed by thyroid nuclide imaging; (2) nodules that are purely cystic on ultrasound; and (3) nodules that are highly suspected to be malignant on ultrasound imaging.
FNAB is not recommended for thyroid nodules <1 cm in diameter, but ultrasound-guided FNAB may be considered in the presence of: (1) ultrasound suggestive of malignant nodules; (2) abnormal ultrasound images of cervical lymph nodes; (3) history of cervical radiation exposure or radiation contamination in childhood; (4) history or family history of thyroid cancer or thyroid cancer syndrome; (5) abnormally elevated serum Ct (calcitonin) levels. abnormally elevated.
The success rate and diagnostic accuracy of ultrasound-guided FNAB is higher than that of palpated FNAB. To improve the accuracy of FNAB, the following methods can be used: repeat 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 diagnostic cytopathologists are also important to ensure the success rate and diagnostic accuracy of FNAB.
There is a lack of strong evidence for the optimal frequency of follow-up of thyroid nodules. In most benign thyroid nodules, follow-up can be performed at 6-12 month intervals. For suspected malignant or malignant nodules that are not yet treated, the follow-up interval can be shortened. History taking and physical examination and review of neck ultrasound must be performed at each follow-up visit. Some patients (those with abnormal thyroid function found during the initial evaluation, those treated with surgery, TSH suppression therapy or 131I) also need to be followed up for thyroid function.
If nodules are found to be significantly growing during follow-up, special attention should be paid to the presence of symptoms, signs (e.g., tearing of the voice, difficulty breathing/swallowing, fixed nodules, enlarged lymph nodes in the neck, etc.) and ultrasound signs that suggest nodule malignancy. “Significant growth” is defined as an increase in nodule volume of more than 50% or at least 2 diameter lines of more than 20% (and more than 2 mm), which is an indication for FNAB; for cystic nodules, the decision to perform FNAB is based on the growth of the solid portion.
Question 9: Treatment of benign thyroid nodules
Most benign thyroid nodules require only regular follow-up and no specific treatment. In a few cases, surgery, TSH suppression therapy, radioiodine (RAI), or 131I therapy, or other treatments are available.
Question 10: Surgical treatment of benign thyroid nodules
Surgery for thyroid nodules may be considered in the following cases: (1) when there are local pressure symptoms associated with the nodule; (2) when there is a combination of hyperthyroidism and medical treatment has failed; (3) when the mass is located in the posterior sternum or mediastinum; and (4) when the nodule is growing progressively and is clinically considered to have a tendency for malignant transformation or a combination of high-risk factors for thyroid cancer. Those who strongly request surgery because of appearance or excessive ideological concerns affecting normal life can be considered as relative indications for surgery.
The principle of surgery for benign thyroid nodules is: complete removal of thyroid nodules while preserving as much normal thyroid tissue as possible. The use of total/near-total thyroidectomy is recommended with caution. The latter is indicated for nodules that are diffusely distributed bilaterally in the thyroid gland, making it difficult to preserve more normal thyroid tissue intraoperatively. Intraoperative care should be taken to protect the parathyroid glands and the recurrent laryngeal nerve.
Question 11: Non-surgical treatment of benign thyroid nodules
The principle of TSH suppression therapy is to suppress the serum TSH level to the low limit of normal or even below the low limit, in order to reduce the size of thyroid nodules by suppressing the growth-promoting effect of TSH on thyroid cells. In iodine-deficient areas, TSH suppression therapy may help to shrink nodules, prevent new nodules from appearing, and reduce the size of nodular goiter; in non-iodine-deficient areas, TSH suppression therapy may also shrink nodules, but its long-term efficacy is uncertain and nodule regrowth may occur after discontinuation; TSH partial suppression regimens (TSH controlled at the lower limit of the normal range, i.e., 0, 4-0, 6 mUA ) has similar efficacy in reducing nodule volume compared with the TSH complete suppression regimen (TSH controlled at < 0,1 mUA). As for side effects, long-term TSH suppression can lead to subclinical hyperthyroidism (reduced TSH, normal FT3 and FT4), cause discomfort and some adverse effects (e.g., increased heart rate, atrial fibrillation, enlarged left ventricle, increased myocardial contractility, impaired diastolic function, etc.), and result in reduced bone mineral density (BMD) in postmenopausal women. On balance, the routine use of TSH suppression therapy for benign thyroid nodules is not recommended; it may be considered in younger patients with small nodular goiters; if used, the goal is partial TSH suppression.