I. What is a thyroid nodule?
A thyroid nodule is an isolated lesion in the thyroid gland that is palpable and can be detected on ultrasound as distinct from the surrounding tissue. A nodule that is palpable but not confirmed on ultrasound is not diagnosed as a thyroid nodule. Thyroid nodules are not a single thyroid disorder, but can manifest in a variety of thyroid disorders, including degenerative thyroid disease, inflammation, autoimmune disease, tumors and other lesions, all of which are collectively referred to as thyroid nodules until their nature is clarified.
What is the incidence of thyroid nodules?
Epidemiological surveys have shown that 5% of women and 1% of men living in non-iodine deficient areas have palpable thyroid nodules. With high-resolution ultrasound, the detection rate of thyroid nodules in the population can be as high as 19% to 67%, of which 5% to 10% are thyroid cancer. In iodine-deficient areas, the incidence of thyroid nodules is higher. At present, the incidence of thyroid nodules is apparently increasing year by year all over the world, and the reason for this is not clear, except for the increase in the rate of diagnosis.
3. What is the classification and etiology of thyroid nodules?
Thyroid nodules are classified into two categories: benign and malignant, the majority of which are benign.
The common diseases causing benign thyroid nodules are as follows.
(a) Simple goiter;
(b) Thyroiditis: including
1. subacute thyroiditis
2. chronic lymphocytic thyroiditis
3, aggressive fibrous thyroiditis;
(c) Thyroid adenoma.
The common disease causing malignant thyroid nodules is thyroid cancer, including papillary thyroid cancer, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. The majority of these are papillary carcinomas, accounting for 90% of cases. Other rare malignant thyroid nodules include metastatic carcinoma, lymphoma, etc.
What are the dangers of thyroid nodules? Is thyroid cancer very scary?
The majority of benign thyroid nodules are not harmful. Larger thyroid nodules may compress the surrounding trachea, esophagus and laryngeal nerve, causing dyspnea, difficulty in swallowing or hoarseness.
Most thyroid cancers are not very scary. Most of the thyroid malignant tumors are well differentiated, most of them are papillary or follicular carcinoma, with slow development, good treatment effect and good prognosis, and their ten-year survival rate is between 80-95%. The average follow-up of 162 patients with papillary carcinoma diagnosed by FNA was 5 years, and it was found that 70% of the lesions did not change in volume. Medullary thyroid carcinoma is moderately malignant, with a 10-year survival rate between 70% and 80%. Undifferentiated carcinoma is rare, but the treatment is very poor and the survival rate is low.
V. If I find a thyroid nodule, how do I know if it is benign or malignant?
The diagnosis of a thyroid nodule includes a thorough history taking and physical examination and laboratory, imaging and cytology examinations.
History taking and physical examination should focus on the parts related to thyroid cancer, such as any history of head and neck radiation exposure, nuclear exposure (before 14 years old), family history of thyroid cancer in first-degree relatives, whether thyroid nodules are growing rapidly, whether they are accompanied by hoarseness, vocal cord paralysis and enlarged and fixed ipsilateral cervical lymph nodes, etc. If any of these conditions exist, you need to be alert to the possibility of thyroid cancer.
Laboratory tests include serum thyroid stimulating hormone (TSH), serum thyroglobulin (Tg) and serum calcitonin. A low TSH indicates that the nodule may be secreting thyroid hormones, and most of these nodules are benign and rarely malignant. An elevated TSH indicates the possibility of Hashimoto’s thyroiditis with hypothyroidism. Serum thyroglobulin (Tg) is not specific for the diagnosis of thyroid cancer and is only used to monitor recurrence or metastasis after thyroid cancer surgery or isotope therapy. Serum calcitonin measurement is not routinely performed. In unstimulated cases, serum calcitonin >100 pg/ml suggests the possible presence of medullary thyroid carcinoma.
Imaging tests include thyroid ultrasound and thyroid nuclide imaging. When the serum TSH level is below normal, a thyroid nuclear scan should be performed to understand the functional status of the nodule. If a nodule is hot, it is rarely malignant.
High-resolution color ultrasonography of the thyroid is the preferred and routine imaging test for evaluation and follow-up of thyroid nodules with the best potency ratio. By understanding the location, morphology, size, number of nodules, state of nodule margins, internal structure, echogenic features, blood flow status and cervical lymph nodes, most can initially identify the nature of the nodule, with an accuracy rate of 80-85% at our institution. The ultrasound features that suggest a high probability of malignancy are (see Table 1): microcalcifications, marked hypoechogenicity, disorganized internal blood flow, irregular margins, anterior-posterior diameter of the nodule cross-section greater than the left-right diameter (longitudinal/transverse ratio >1) and the presence of ipsilateral cervical lymph node abnormalities (cystic changes, microcalcifications, loss of lymphatic portals and round appearance, disorganized blood flow). No single or several ultrasound features can identify all malignant nodules, and a comprehensive analysis is necessary. Papillary thyroid carcinoma usually presents as a hypoechoic parenchymal or predominantly parenchymal cystic nodule with irregular margins and increased blood flow within the nodule. Microcalcifications (less than or equal to 2 mm) are highly suggestive of papillary thyroid carcinoma, but are sometimes difficult to distinguish from gliosis. Microcalcifications should not be confused with punctate strong echogenicity with comet tails within a cystic or gelatinous nodule. When punctate strong echogenicity with a posterior comet tail is present in a thyroid nodule, it is often a dense colloid, which is mostly found in the center or periphery of the cystic nodule due to reverberant artifacts created when ultrasound contacts the crystals within the colloid. When this sign is present there is a greater than 85% probability that it is benign. Follicular carcinoma, on the other hand, is more often seen as hyperechoic or isoechoic with a thick irregular halo. Follicular carcinomas smaller than 2 cm are usually not associated with metastases. Some ultrasound features are highly suggestive of benignity. Purely cystic lesions are rarely malignant. Spongiotic lesions (multiple tiny cystic lesions occupying more than 50% of the nodule volume) are 99.7% benign.
Fine needle aspiration biopsy (FNA) of the thyroid gland is the most accurate method to distinguish benign and malignant thyroid nodules other than surgery, with an accuracy rate of 90% in large foreign medical centers, but in China, due to the limitations of the level of pathological cytology, sensitivity, specificity and accuracy are limited, and it is difficult to meet clinical requirements, so it is not yet widely used. Fine needle aspiration pathology (FNA) should be considered if
① No suspicious signs on ultrasound. Solid nodules with a diameter greater than 1.5 cm. or cystic nodules greater than 2 cm in diameter.
② Ultrasound with suspicious signs (hypoechoic, microcalcifications, infiltrative irregular margins, blood flow rich disorder in the center of the nodule, nodule aspect/transverse ratio >1, etc.). If 2 of the above are present, the likelihood of malignancy is significantly increased. If 3 of these items are present, the likelihood of malignancy is close to 80%.) The likelihood of malignancy is close to 80%. Solid nodules, >1 cm in diameter, or cystic nodules, >1.5 cm in diameter. Although early detection and diagnosis of small tumors may be clinically important, given that incidentally detected microscopic thyroid cancers are rarely invasive and the accuracy of FNA of nodules that are too small is limited, smaller suspicious thyroid nodules (less than 0.5 cm) can generally be detected without FNA, with regular follow-up by ultrasound. For patients with high suspicion of malignancy by ultrasound or a desire for excisional biopsy, surgery may also be considered Excisional biopsy.
③Nodules of any size, but ultrasound suggests suspicious extraperitoneal invasion or suspicious cervical lymph node metastasis (mainly manifested by microcalcifications, cystic changes, structural abnormalities showing disappearance of lymphatic portals and circular appearance, and blood flow rich disorder).
④ Nodules of any size, childhood (before age 14) history of external head and neck radiation therapy or exposure to ionizing radiation, history of prior thyroid cancer, positive 18FDG-PET scan, history of thyroid cancer or multiple endocrine neoplasia type 2 in a first-degree relative, or elevated calcitonin.
Evaluation of multinodular goiter: The risk of malignancy in multinodular goiter is the same as the risk of malignancy in a single node. Color ultrasonography of the thyroid is recommended to understand the ultrasonographic features of the nodules. FNA is performed on nodules with suspicious malignant ultrasonographic features, or on the largest of these nodules if there are no nodules with suspicious malignant ultrasonographic features.
VI. How to treat malignant thyroid nodules?
After surgery, the choice of iodine 131 therapy, radiation therapy or endocrine thyroxine suppression therapy will be decided according to different cases (see the article “Treatment of thyroid cancer” for details).
For micro papillary thyroid cancer (<1.0cm) found on physical examination, if there is no tendency to invade surrounding organs, no lymph node metastasis or distant metastasis, no family history of thyroid cancer, no history of childhood radiation therapy and other high-risk factors, the patient can choose not to operate immediately and be closely monitored according to his or her wish. According to the long-term observation of bulk cases, about 90% of micro papillary thyroid carcinoma have no obvious progression, and about 10% of micro papillary thyroid carcinoma have more obvious progression and need surgery, most of which have little effect on the outcome after timely surgical treatment. For patients of advanced age and with severe cardiopulmonary and other organ comorbidities that make surgery more risky, close observation may be a better choice overall. However, for patients with invasion of the thyroid peritoneum, invasion of the trachea, multiple carcinomas, or with suspicious metastasis of the surrounding lymph nodes, observation is not advisable and surgery is needed as soon as possible.
VII. How to treat benign thyroid nodules?
Most benign thyroid nodules do not require treatment, but only follow-up observation. A few require radiofrequency ablation therapy or surgery.
Currently, there are seven treatment methods for benign thyroid nodules: follow-up observation, thyroid hormone suppression therapy, surgery, radioactive iodine therapy, alcohol intervention therapy, laser coagulation therapy, and high-frequency ultrasound ablation (radiofrequency ablation) therapy.
The effectiveness and safety of thyroid hormone therapy for thyroid nodules has been questioned. A recent meta-analysis showed that suppression of TSH to below 0.3 mU/L resulted in no significant reduction in nodules compared to controls; suppression of TSH to below 0.1 resulted in a significant reduction in new nodules, but a significant increase in the risk of cardiac lesions such as atrial fibrillation. Moreover, thyroid nodules can grow again after discontinuation of the drug. In addition, thyroid hormone suppression therapy does not reduce the recurrence rate after thyroid cyst aspiration. Recently, a clinical meta-analysis involving nine randomized studies showed that thyroid hormone suppression therapy did significantly reduce the size of thyroid nodules compared to no treatment or placebo, but the effectiveness of long-term treatment was significantly reduced, while nodule size increased significantly after discontinuation. Considering its possible side effects of heart disease and osteoporosis, this treatment is not recommended for routine use in benign nodules. Radioactive iodine treatment of thyroid nodules has significant limitations, reducing the size of the nodules by only 34-55%. Alcohol intervention has good results, but its range of indications is small and is mainly used for purely cystic nodules, or cystic nodules consisting mostly of fluid. Laser coagulation and high-frequency focused ultrasound ablation (radiofrequency ablation) are emerging treatment methods whose effectiveness and safety are still under further research verification. In recent years, more and more data show that radiofrequency ablation can achieve better results in the treatment of benign thyroid nodules. The rate of recurrent nodules after surgery for benign thyroid nodules is high, so surgery is not the primary treatment for patients with this type of disease.
A series of clinical observations and follow-up studies have found that thyroid nodules can become larger, shrink, or remain unchanged. A 15-year study showed that 13.5%, 41.5%, or 33.6% of nodules grew, shrank, or remained unchanged, respectively, and 11.4% of nodules disappeared completely. A more recent study found that most nodules shrank or remained unchanged at 39 months of follow-up, with no more than 1/3 of nodules increasing in size. benign thyroid nodules have a low probability of malignancy. In 134 patients with pathologically confirmed benign nodules followed for 9-11 years, only 1 case (0.7%) developed papillary carcinoma, and 43% of the nodules shrank spontaneously. Incidental thyroid tumors are common, but their prognosis is very good. In fact, malignant lesions in surgical specimens of incidental nodules were 1.5%-10%; malignant lesions were found in 4.0%-7.4% of ultrasound-guided FNAC specimens, 4.7% in single nodules and 2.7% in multiple nodules, most of which were papillary carcinomas, while papillary thyroid carcinomas developed slowly and were the least malignant. Therefore, it is unanimously accepted by international scholars that no overly aggressive treatment is needed for benign thyroid nodules, and follow-up is the most appropriate treatment for most benign nodules.
Under what circumstances do benign thyroid nodules require surgery?
Surgery is indicated for benign thyroid nodules under the following circumstances.
(1) If the nodule affects the aesthetics and the patient requests surgery.
(2) Those with symptoms of tracheoesophageal compression.
(3) Those with hyperthyroidism.
(4) Post-thoracic goiter.
(5) Cystic nodules combined with intracapsular hemorrhage or recurrence after repeated puncture and aspiration, etc.
(6) Ultrasonography suggestive of adenoma.
(7) Those with high suspicion of malignancy on ultrasonography.
(8) FNA examination confirms the diagnosis or cannot exclude malignant change. there are four types of FNA results: benign, malignant, suspected malignant and undiagnosed. For fine needle aspiration pathological examination confirmed or suspected papillary carcinoma, medullary carcinoma, undifferentiated carcinoma (accuracy rate of FNA as carcinoma >95%, accuracy rate of suspected malignancy 50-60%), and follicular tumor or eosinophilic tumor (20-30% possibility of malignancy), surgical treatment should be performed. Follicular lesions of uncertain significance require repeat puncture, close observation, or consideration of surgery (based on clinical grounds such as ultrasound suspicious features or growth rate). If the specimen is insufficient and undiagnostic, repeat puncture or consider surgery for solid nodules, and re-puncture of the suspicious area or consider surgery for cystic nodules. Non-diagnostic means that the biopsy results do not meet the specific diagnostic criteria available and are caused by operator inexperience, too little aspirate, too small nodules, or the presence of cystic lesions, and must be repeated, preferably under ultrasonographic guidance. Some nodules that are never diagnosed based on cytologic findings during repeated biopsies are likely to be diagnosed as malignant at the time of surgery and require surgical treatment.
For those with benign lesions reported by ultrasound and fine-needle aspiration pathology, observation (repeat ultrasound after 6-12 months, with an interval of 3-5 years if stable for 1-2 years) is an option, and if the nodule grows (increase in both longitudinal and transverse diameter of the nodule by more than 20% within 6-18 months, i.e., an increase in volume of at least 50%), further aspiration may be performed or surgery may be considered.
Thyroid nodules are not evaluated with a thyroid nuclear scan in pregnant women, but are otherwise evaluated in the same way as in non-pregnant women. In pregnant women with a diagnosis of a malignant thyroid nodule, ultrasound monitoring should be performed to reduce the risk of miscarriage, and surgery before 24 weeks of gestation should be an option if the nodule continues to grow. If the nodule is stable or if it is diagnosed late in pregnancy, surgery should be performed after delivery. The progression of thyroid cancer detected during pregnancy is not faster than that of non-pregnant patients, and there is no difference in survival and recurrence rates. Delaying treatment for 1 year mostly has no significant adverse effect on prognosis.