Thyroid nodules are a common clinical problem. They are usually detected by doctors during physical examinations or by people around them during their daily work. In Europe and the United States, 5% ~ 7% of the general population has thyroid nodules. If ultrasound is used, the chance of finding a thyroid nodule that cannot be felt by hand is higher, reaching 50% in people over 50 years old. In China, there is no large-scale epidemiological data showing the incidence. However, recent studies have found a high incidence of thyroid nodules in the middle-aged and elderly population in the northwest, with ultrasound-detected nodules in 37% of men and 46% of women, with nodules larger than 1 cm accounting for 1/3 of cases.
Most of the thyroid nodules that can be felt clinically are benign, and only about 10% are malignant. Therefore, most people with thyroid nodules do not need to be nervous. Clinical reports on thyroid surgery in China show that most hospitals perform thyroidectomy for malignant tumors accounting for only 10%-15% of all thyroid surgeries, which indicates that most cases of thyroid surgery are benign, and also indicates that the surgical conditions for thyroid nodules in China are too broad and not selective enough. In contrast, I have personally seen that in top-tier thyroid surgery in the United States, the percentage of surgeries for thyroid cancer accounts for 40% of total thyroid surgeries. In recent years, in China, the proportion of thyroid cancer to total thyroid surgery in large teaching hospitals or head and neck surgery departments of large cancer hospitals has increased significantly, reaching 40%-50%, and in some cases even up to 80%. This indicates that thyroid surgery in China has developed rapidly in recent years. In 2012, we published our own “Guidelines for the management of thyroid nodules”, combining elements of European and American guidelines.
The thyroid gland is located in the middle of the front of the neck and is usually not palpable when it is normal in size. A thyroid nodule is a nodular lesion that is palpated in the thyroid gland and confirmed by ultrasound. It is characterized by up and down movement of the nodule with swallowing movements. However, a thyroid nodule that is not detected by palpation but is found accidentally by ultrasound should be treated the same as a nodule that is palpated, because both have the same chance of being malignant when they are the same size. It is generally accepted that thyroid nodules larger than 1 cm have the potential for thyroid cancer and require further management. The diagnostic principle of thyroid nodules is to evaluate the possibility of malignancy. It can be evaluated from the following aspects.
I. Medical history and physical examination
Once a thyroid nodule is found, it should be carefully analyzed from medical history and physical examination for malignant possibility. Most thyroid nodules grow insidiously and are asymptomatic when they are occasionally detected by physical examination, but this does not exclude malignancy. The rate of growth of the nodule should be noted in the history, and if the nodule continues to grow over a period of months, malignancy should be suspected. If it increases significantly in a short period of time, the possibility of undifferentiated carcinoma should be considered in elderly patients. If the enlarged nodule is not obvious but combined with hoarseness, difficulty in swallowing, coughing and shortness of breath, or if there is a history of thyroid cancer in the past and the nodule appears, it is highly suggestive of malignancy. Radiation is a clear cause of thyroid nodules and thyroid cancer, and the incidence of thyroid cancer in children exposed to radiation increased significantly after the nuclear accident at the Chernobyl nuclear power plant. Some studies have shown that 1 out of 200 head and neck CT exams will result in thyroid cancer. A history of previous oncologic treatment should be noted in those with a history of total body irradiation or radiation therapy to the head, neck and upper chest. Only 5% of papillary carcinomas, 20% of medullary carcinomas and multiple endocrine neoplasia type 2 have genetic characteristics, so attention should be paid to first-degree relatives with a history of thyroid cancer. The patient’s own characteristics are also a high risk factor for thyroid cancer. For example, male patients, adolescents younger than 20 years old and elderly people older than 70 years old have a high chance of having malignant thyroid nodules.
The physical examination focuses on the characteristics of the thyroid nodules and the condition of the lymph nodes in the neck. Malignancy should be suspected if the thyroid nodule is hard, with poorly defined borders and poor mobility, with the hard texture being the predominant feature. Malignancy should be highly suspected if accompanied by ipsilateral enlargement of the cervical lymph nodes or vocal cord paralysis. In the past, emphasis was also placed on differentiating whether the nodes were solitary or multiple, and it was thought that solitary nodes had a higher chance of malignancy than multiple nodes. However, several recent studies have shown that for the individual patient, the chances of malignancy are equal for single and multiple nodes. This change in concept is largely based on the widespread use of ultrasound. One study found that up to 50% of palpated solitary thyroid nodules were actually multiple nodules on ultrasound exploration.
Thyroid function tests
The most important indicator in thyroid function tests is blood TSH. If TSH is lower than normal, suggesting elevated thyroid function, a nuclear scan should be performed to find out if there are high-functioning nodules. High-functioning nodules are rarely malignant. Thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab), although not helpful in identifying benign or malignant, may indicate the presence or absence of thyroiditis. It is not possible to determine the presence of thyroid cancer by blood sampling. However, medullary carcinoma is rare and accounts for less than 5% of thyroid cancer, so it is not necessary to check this index if you have thyroid nodules.
Ultrasound examination
Ultrasound can detect the number of nodules, their size and cystic solidity. If a nodule is not confirmed by ultrasound on palpation, it may be due to a change in the shape of the thyroid gland, which can be seen in Hashimoto’s thyroiditis.
Ultrasound is helpful in determining the benignity of thyroid nodules. Ultrasound images of thyroid cancer are characterized by hypoechoic nodules; microcalcifications; unclear borders and increased blood flow, nodule height greater than width, especially microcalcifications are most important. It is also helpful to detect lymph nodes in the neck that are not clinically palpable. Elastic ultrasound showing stiffer ones also suggests a high chance of malignancy.
Thyroid nuclear scan
Ninety-five percent of nodules do not accumulate isotopes, so more than 80 percent are “cold nodules. Only 10-20% of “cold nodules” are malignant. The 10% of nodules with “cool nodules” or “warm nodules” are due to the presence of normal glandular tissue in front of or behind the nodule, and 10% are malignant. The nucleus scan is no longer used abroad as a routine test to identify benign and malignant thyroid nodules.
Five, needle-needle aspiration cytology (FNAC)
FNAC has brought about a fundamental change in the management of thyroid nodules and is the most valuable method for determining the benignity and malignancy of nodules, and is the greatest advancement in thyroid surgery in the past 50 years. In the last 20 years or so, it has become a routine test for thyroid nodules abroad. Unfortunately, in China, thyroid FNAC is far from being recognized and popular, and very few units routinely apply it. Therefore, it is an important task to improve the diagnosis of thyroid tumors in China by training relevant personnel and carrying out FNAC in combination with their respective conditions.
VI. The diagnostic results of FNAC of thyroid nodules can be divided into 4 categories.
1, benign: thyroiditis, colloid nodules or cysts, accounting for about 70%.
2. suspicious: follicular cell or eosinophilic tumors, or suspected papillary carcinoma, accounting for 10%.
3. malignant: including papillary carcinoma, medullary carcinoma, undifferentiated carcinoma, lymphoma and metastatic carcinoma, accounting for 5 per cent
4. unable to evaluate: because of insufficient specimens or unsatisfactory smears.
This shows that FNAC is diagnostic for more than 80% of nodules. The diagnostic rate can be improved by puncturing the solid part of the nodes under ultrasound guidance. For multiple nodes, FNAC is usually performed on the largest nodes and those with ultrasound indication of possible malignancy, and the report is usually available on the same day.
VII. Core needle biopsy (CNB)
Since fine needle aspiration requires trained cytologists, which is lacking in China at this stage, many large hospitals are currently performing core needle aspiration of thyroid nodules. A small thin strip of thyroid tissue is obtained by coarse needle aspiration, usually also under ultrasound guidance, using local anesthesia, and it takes about 3 days for the pathology department to issue a report.
VIII. Treatment of thyroid nodules
1. Based on the results of FNAC
If the nodule is benign, it can be observed until it becomes a symptom of pressure or affects the aesthetics before surgery is considered. It is controversial whether to give thyroid hormone (eugenol) to inhibit nodule growth. Recent analysis of foreign studies has shown that there was no difference in the proportion of nodules that were reduced by half in the group treated with eugenol compared to the control group that did not take eugenol. A recent clinical study in Shanghai, China, found that the maximum diameter of nodules was significantly reduced after suppression treatment, while there was no change in the control group. In view of the risk of levothyroxine causing osteoporosis and atrial fibrillation in the elderly, I agree in my clinical work that suppressive therapy with eugenol should not be routinely applied in areas where iodized salt is already supplemented.
The chance of malignancy in cystic nodules is less than 3%. Since the more liquid components in a cyst, the less chance of malignancy, simple cysts can be treated by aspiration. The recurrence rate of aspiration treatment can be more than 50%, and for recurrence, 95% ethanol can be injected into the cyst after re-aspiration or aspiration. If there are more than 2 recurrences or if the cyst is larger than 4 cm, surgery is indicated.
For FNAC suggestive of follicular adenoma or eosinophilic adenoma, since about 20% of patients in this group are malignant, surgery is recommended to perform lobectomy with isthmus on the side of the lesion to clarify the diagnosis. Since the diagnosis of follicular adenoma is difficult by freezing, it is necessary to rely on the results of paraffin section.
If FNAC is malignant, surgery is indicated.
For those who cannot be evaluated, FNAC should be performed again under ultrasound guidance; most of them can be diagnosed cytologically. If the evaluation is still not possible, surgery is required to confirm the diagnosis.
Based on the results of FNAC, surgery is indicated and the percentage of thyroid cancer surgery in famous endocrine surgery centers abroad is already about 40% of all thyroid surgeries. The following diagram shows the steps for the diagnosis and management of thyroid nodules.
2.No FNAC results
The majority of domestic units have not yet carried out FNAC, which can also be based on the results of coarse needle aspiration. Except for thyroid nodules with symptoms of pressure, affecting aesthetics and hyperfunction, which are considered for surgical treatment, the management of the rest of the nodules is based on the chance of malignancy.
Physical examination reveals a solitary nodule with ultrasound confirmation of solidity and ultrasound suggestive of malignancy should be operated, especially in men, younger and older patients. Since the more liquid components in cysts, the less chance of malignancy, so simple cysts can be treated by aspiration, and recently emerged cysts with larger size are prone to recurrence after aspiration due to heavy adhesion of surrounding tissues edema, and can be operated. Mixed nodules with predominantly solid components may be considered for surgery if ultrasound suggests indistinct margins and microcalcifications, among other manifestations. For multiple nodules, surgery should also be recommended if the most predominant nodule is large, solid, hard, hypoechoic on ultrasound, with indistinct borders or microcalcifications. In multiple nodules, as the number of nodules increases and the diameter of nodules becomes smaller, the chance of malignancy in each nodule decreases. Therefore, multiple nodules smaller than 1~2 cm can be observed. Surgery may also be considered for those who are too burdened to undergo regular observation. If thyroid function is normal during observation, it is not recommended to take eugenol to try to reduce the size of the nodules. See above for reasoning. Observation generally means ultrasound every 6 months for 2 years after the nodule is found, and after no change, ultrasound once a year, which is exactly the frequency of regular checkups for most people.
3.Surgery of thyroid nodules
For thyroid nodules that cannot be excluded as malignant, surgery should be performed to remove the lobe of the affected gland. I do not recommend adenoma or nodule resection or subtotal thyroidectomy. This is because.
(1) after lobectomy, if the nodule is malignant, the diagnosis and treatment will be completed in one visit, which is in accordance with the principles of oncological surgery.
(2) Lobectomy does not miss occult cancer, and if it is malignant, it will not recur locally on the affected side.
(3) After lobectomy, it is not necessary to deal with the affected side when reoperation is needed, which reduces the chance of nerve damage and parathyroid gland misincision due to adhesions.
(4) The recurrence rate of nodular goiter is 25% after surgery, but after lobectomy, there is no risk of recurrence on that side.
(5) The chance of permanent nerve damage is less than 1% with lobectomy by experienced surgeons.
The surgical technique required for lobectomy of the thyroid gland is high. It is well established that routine exposure of the recurrent laryngeal nerve reduces nerve injury, and the parathyroid glands should be carefully identified and their blood supply should be protected as much as possible during surgery. Foreign studies have shown that skilled thyroid surgeons (100 or more thyroidectomies per year) have a significantly lower chance of nerve injury and parathyroid injury than the average surgeon.
If FNAC results are not available, the resected specimen should be sent for frozen section examination. Frozen sections can diagnose papillary carcinoma and help in treatment decisions on the operating table, but there are difficulties with follicular carcinoma and eosinophilic carcinoma, and results can only be awaited from paraffin sections.
IX. Post-surgical management of thyroid nodules
Hypothyroidism does not occur in about 90% of patients after lobectomy of the thyroid gland. In patients with nodular goiter, prospective clinical studies have shown that the administration of levothyroxine (eugenol or similar) does not reduce the postoperative recurrence rate; therefore, thyroid hormone supplementation is required only for those with hypothyroidism.
In conclusion, more than 90% of thyroid nodules are benign lesions. Performing FNAC or coarse needle aspiration has clear guidelines for the management of thyroid nodules. Lobectomy should be performed for thyroid nodules whose surgical purpose is to exclude malignancy.