Thyroid nodules and thyroid cancer are frequent and common diseases of the endocrine system. The prevalence of thyroid nodules obtained by palpation is 3-7%, and the prevalence of thyroid nodules obtained by high-resolution ultrasound is 20-76%. The prevalence of thyroid cancer in thyroid nodules is 5-15%.
Definition of thyroid nodules
Thyroid nodules are scattered lesions caused by abnormal localized growth of thyroid cells. A “nodule” that is palpable but not confirmed on ultrasound 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”.
Clinical presentation of thyroid nodules
Most patients with thyroid nodules have no clinical symptoms. When combined with abnormal thyroid function, the corresponding clinical manifestations may occur. Some patients have symptoms of compression such as hoarseness, pressure, and difficulty breathing/swallowing due to nodule compression of surrounding tissues.
The following medical history and physical examination findings are risk factors for thyroid cancer.
1. history of childhood head and neck radiation exposure or exposure to radioactive fallout
2. history of systemic radiation therapy.
A 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 of the thyroid gland. Carney syndrome, Werner syndrome and Gardner syndrome, etc.) past or family history.
4, male.
5, rapid growth of nodules.
6, with persistent hoarseness, dysphonia and exclusion of vocal fold pathology (inflammation, polyps, etc.).
7, with dysphagia or dyspnea.
8. Irregular shape of the nodule and fixed adhesions to the surrounding tissues.
9, with pathological enlargement of the lymph nodes in the neck.
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.
The role of ultrasonography in the evaluation of thyroid nodules
High-resolution ultrasonography is the method of choice for the evaluation of thyroid nodules. Ultrasound of the neck should be performed for palpable suspicion or for “thyroid nodules” suggested by X-ray, computed tomography (CT), magnetic resonance imaging (MRI), or 2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET). 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 assess the presence and size, morphology and structural characteristics of lymph nodes in the neck area.
Certain ultrasound signs can help in the differentiation of benign and malignant thyroid nodules. Almost all thyroid nodules with the following two types of ultrasound changes are benign.
1, purely cystic nodules.
2. Nodules with multiple small vesicles occupying more than 50% of the nodule volume and showing spongy changes are 99.7% benign. In contrast, 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 morphology and margins, halo absence.
4, microcalcifications, 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, internal calcification, poorly demarcated dermatomedullary, disappearance of lymphatic portals, or cystic changes. The ability to identify benign and malignant thyroid nodules by ultrasonography is related to the clinical experience of the ultrasonographer.
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, or other treatments are available.
Surgical treatment of benign thyroid nodules.
Surgery for thyroid nodules may be considered in the following cases.
1. the presence of local pressure symptoms clearly associated with the nodule
2. combined with hyperthyroidism, for which medical treatment is ineffective
3, the mass is located in the posterior sternum or mediastinum
4. Progressive growth of the nodule with clinical consideration of malignant tendency or combined with 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.
Non-surgical treatment of benign thyroid nodules
TSH suppression therapy is based on the principle of applying L-T4 to suppress the serum TSH level to the low limit of normal or even below the low limit, in order to achieve the goal of shrinking thyroid nodules by inhibiting the pro-growth effect of TSH on thyroid cells. In iodine-deficient areas, TSH suppression therapy may help to shrink nodules, prevent new nodules, 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 of the therapy. L) has similar efficacy in reducing nodule volume compared with the TSH complete suppression regimen (TSH control < 0.1 mU/L). As for side effects, long-term TSH suppression can lead to subclinical hyperthyroidism (reduced TSH with normal FT3 and FT4), which can cause discomfort and some adverse effects (e.g., increased heart rate, atrial fibrillation, enlarged left ventricle, increased myocardial contractility, impaired diastolic function) and 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.
131I is primarily used to treat benign thyroid nodules with autonomic uptake and concomitant hyperthyroidism. For nodules with autonomic uptake but without hyperthyroidism, 131I may be a treatment option. 131I therapy is not recommended for thyroid nodules with symptoms of pressure or located behind the sternum. Being pregnant or lactating is an absolute contraindication to 131I treatment. In terms of efficacy, nodules with autonomic function can gradually shrink and thyroid volume can be reduced by 40% on average after 2-3 months of 131I treatment; in cases with hyperthyroidism, symptoms, signs and related complications of hyperthyroidism can gradually improve while nodules shrink, and thyroid function indicators can gradually return to normal. If the hyperthyroidism does not resolve and the nodules do not shrink after 4-6 months of 131I treatment, the patient’s clinical manifestations, relevant laboratory tests and results of thyroid nuclear imaging should be taken into consideration for re-treatment with 131I or other treatment methods. Therefore, it is recommended that thyroid function be tested at least once a year after treatment, and that L-T4 replacement therapy be given promptly if hypothyroidism is detected during monitoring.
Other non-surgical methods for treating benign thyroid nodules include: ultrasound-guided percutaneous ethanol injection (PEI), percutaneous laser ablation (PLA) and radiofrequency ablation (RFA). ablation (RFA), etc. Among them, PEI is effective for benign thyroid cysts and thyroid nodules containing large amounts of fluid, but not for single substantial nodules or multinodular goiters. The possibility of malignant nodules must be ruled out before treatment with these methods.
Overview of DTC
More than 90% of thyroid cancers are DTC, which originate from the follicular epithelium of the thyroid and include mainly PTC and follicular thyroid carcinoma (FTC), with a few Hǔrthle cell or eosinophilic tumors. Most DTCs progress slowly and have a benign course with a high 10-year survival rate. However, certain histologic subtypes (hypercellular, columnar cell, diffuse sclerosing, solid subtypes of PTC and extensive infiltration of FTC) are prone to extrathyroidal invasion, vascular invasion and distant metastasis, with a high recurrence rate and relatively poor prognosis.
Poorly differentiated thyroid cancer also belongs to the category of DTC. These tumors are relatively rare and have insular, beam-like or solid structures, but do not have the typical nuclear features of PTC and have at least one of the following three morphological features: nuclear distortion, nuclear schizophrenia ≥ 3/10 high magnification field, and necrosis. The clinico-biological characteristics of this type of tumor are highly aggressive, prone to metastasis, and poor prognosis, which is one of the difficulties in the treatment of DTC at present.
The treatment methods of DTC mainly include: surgical treatment, postoperative 131I treatment and TSH suppression treatment. The overall trend of DTC treatment is individualized and comprehensive treatment.
How to determine the thyroidectomy procedure for DTC surgery
The following factors should be considered when determining the extent of thyroidectomy for DTC surgery: tumor size; presence or absence of invasion of surrounding tissues; presence or absence of lymph nodes and distant metastases; unifocal or multifocal; history of radiation exposure during childhood; family history of thyroid cancer or thyroid cancer syndrome; gender, pathological subtype and other risk factors. The principles of surgical management should be refined according to the clinical TNM (cTNM) stage, the risk of tumor death/recurrence, the pros and cons of various surgical procedures and the patient’s wishes, and should not be generalized.
The main thyroidectomy procedures for DTC include total/near-total thyroidectomy and thyroid lobectomy + isthmus. Total thyroidectomy is the removal of all thyroid tissue with no visible thyroid tissue remaining, while subtotal thyroidectomy is the removal of almost all visible thyroid tissue (with <1g of non-neoplastic thyroid tissue, such as the laryngeal nerve into the larynx or the parathyroid gland).
Total/near-total thyroidectomy may provide the following benefits for patients with DTC.
1. treatment of multifocal lesions in a single visit
2. facilitates postoperative monitoring of tumor recurrence and metastasis
3. facilitating postoperative 131I therapy.
4. reduce the chance of tumor recurrence and reoperation (especially for patients with intermediate and high-risk DTC), thus avoiding the increased incidence of serious complications due to reoperation.
5. accurately assessing the postoperative staging and risk stratification of patients.
On the other hand, permanent hypothyroidism will inevitably occur after total/proximal total thyroidectomy; moreover, this procedure requires a higher level of surgeon expertise and an increased probability of impaired postoperative parathyroid function and/or laryngeal recurrent nerve injury.
Suggested indications for total/near-total thyroidectomy for DTC include.
1. history of head and neck radiation exposure or radioactive fallout exposure during childhood.
2, primary foci >4 cm in maximum diameter.
3, multiple cancerous foci, especially bilateral ones.
4, poor pathological subtypes, such as: hypercellular, columnar cell, diffuse sclerosing, solid subtype of PTC, extensive infiltrative type of FTC, and hypofractionated thyroid cancer.
5. having distant metastases and requiring postoperative 131I treatment.
6, with bilateral lymph node metastasis in the neck.
7.Extra-glandular invasion (such as tracheal, esophageal, carotid artery or mediastinal invasion).
The relative indications for total/near-total thyroidectomy are: maximum tumor diameter between 1-4 cm, with high risk factors for thyroid cancer or combined with contralateral thyroid nodules.
Compared with total/near-total thyroidectomy, lobectomy + isthmus is more favorable to protect parathyroid function, reduce contralateral laryngeal nerve injury, and preserve some thyroid function; however, this procedure may miss microscopic lesions in the contralateral thyroid gland, which is not favorable for postoperative monitoring by serum Tg and 131I whole-body imaging, and if 131I therapy is assessed to be required after surgery, a reoperation to remove the residual thyroid gland.
Therefore, the recommended indications for thyroid lobectomy + isthmus are: single DTC confined to one lobe of the gland with a primary tumor ≤1 cm, low risk of recurrence, no history of childhood head and neck radiation exposure, no cervical lymph node metastases or distant metastases, and no nodules in the contralateral lobe. The relative indications for thyroid lobectomy + isthmus are: single DTC confined to one lobe with a primary tumor ≤ 4 cm, low risk of recurrence, no nodules in the contralateral lobe, and microinfiltrative FTC.
The meaning of 131I therapy after DTC surgery
131I is one of the important tools for postoperative treatment of DTC. 131I treatment includes two levels: first, 131I ablation for thyroid remnant after DTC surgery (131I ablation for thyroid remnant); second, 131I ablation for metastatic foci of DTC that cannot be removed by surgery (131I clearing).
Indications for 131I nail clearing treatment
The significance of 131I nail clearing after DTC surgery includes.
1.It facilitates the monitoring of disease progress by serum Tg and 131I whole body scan (WBS).
2. It is the basis of 131I focal clearance treatment.
3, WBS and single photon emission computed tomography (SPECT)/CT fusion imaging [59] after nail clearing are helpful for re-staging DTC.
4, Possible treatment of underlying DTC lesions.
The indications for postoperative 131I nail clearing therapy are still controversial, and the main question focuses on whether low-risk patients benefit from it. Combining ATA’s recommendation, the actual situation in China and clinical experience, it is recommended to perform real-time evaluation of postoperative DTC patients and selectively implement 131I nail clearing therapy according to TNM staging. Overall, 131I nail clearing therapy can be considered for all DTCs except those with cancer foci <1 cm and no extra-glandular infiltration, lymph nodes or distant metastases. 131I nail scavenging is contraindicated during pregnancy, lactation, planned short-term (6-month) pregnancy, and for those who cannot follow radiation protection instructions.
Preparation for 131I nail clearing treatment
If a patient has an indication for nail clearing therapy but excessive residual thyroid tissue is found during the pre-treatment evaluation, the patient should be advised to first undergo re-excision of as much residual thyroid tissue as possible, otherwise the effectiveness of nail clearing is more difficult to ensure. Although nail clearing may remove residual thyroid lobes, it is not recommended as an alternative to surgery. If surgically resectable DTC metastases are identified during the evaluation prior to nail clearing, reoperation should be performed first. Direct thyroidectomy may be considered only if the patient has a contraindication to reoperation or refuses reoperation. For patients with poor general status, concomitant serious diseases or other high-risk malignancies, priority should be given to correction of general status and treatment of concomitant diseases before considering nail clearing treatment.
In normal thyroid follicular epithelial cells and DTC cells, the sodium iodide symporter (NIS) is expressed in the cytosolic membrane and can fully uptake 131I when stimulated by TSH, therefore, elevated serum TSH levels are required prior to nail cleansing therapy. Serum TSH >30mU/L significantly increases 131I uptake by DTC tumor tissue. Elevating TSH levels can be achieved in two ways.
1. Elevating endogenous TSH levels: withholding L-T4 for 4-6 weeks after total/near-total thyroidectomy or (for those who have started TSH suppression therapy) discontinuing L-T4 for at least 2-3 weeks to raise serum TSH levels above 30 mU/L.
2. Use of recombinant human TSH (rhTSH): intramuscular injection of rhTSH 0.9 mg daily for two days prior to nail clearing therapy, without discontinuing L-T4. rhTSH is particularly indicated for elderly patients with DTC, those who cannot tolerate hypothyroidism, and those whose TSH elevation cannot reach the target after discontinuing L-T4.
Currently, rhTSH has been approved for adjuvant nail cleansing therapy in many countries in Europe, the United States, Asia, and Hong Kong and Taiwan in China, but this drug has not yet been registered for marketing in mainland China.
Diagnostic whole-body nuclide imaging (Dx-WBS) can be performed prior to nail clearing treatment and its role includes.
1, to assist in understanding the presence of iodine-intake metastases
2.To assist in the calculation of 131I treatment dose.
3. to predict the effect of body iodine load on nail clearance therapy. However, it has also been suggested that Dx-WBS is not necessary prior to nail clearing because the low dose of 131I used in Dx-WBS is almost entirely taken up by residual thyroid tissue, does not effectively demonstrate iodine uptake metastases, and may cause “stuttering”.
”Stunning” means that the low dose 131I used for diagnostic purposes reduces the uptake of normal thyroid tissue and iodine uptake metastases to the high dose 131I subsequently used for treatment. Ways to reduce “stuttering” include: using low-dose 131I (<5mCi) and administering nail clearance within 72 hours of diagnostic dosing; replacing 131I with 123I as the diagnostic agent for DxWBS, but 123I is difficult and expensive to source.
The efficacy of 131I is dependent on the dose of 131I entering the residual thyroid tissue and within the DTC lesion. Stable iodine ions in the body compete with 131I to enter the thyroid tissue and DTC lesions, so patients are required to be on a low iodine diet (<50 μg/d) for at least 1-2 weeks prior to 131I nail clearing treatment. Iodine-containing contrast agents and medications (e.g., amiodarone) must be avoided during the treatment waiting period. If iodine-containing contrast agents or foods or medications containing high doses of iodine have been used prior to nail clearing treatment, treatment should be withheld. Urinary iodine levels can be monitored when available.
Pregnancy testing is required for women of childbearing age prior to the administration of nail clearing treatment. In addition, patients should be introduced to the purpose of treatment, the process of implementation, possible side effects after treatment, and be instructed on radiation safety protection.
Short-term side effects of 131I nail clearing treatment
Therapeutic doses of 131I cause direct radiation damage to DTC lesions, residual thyroid tissue, adjacent tissues and other normal tissues and organs that can take up iodine, resulting in varying degrees of radioactive inflammatory reactions. Common side effects in the short term (1-15 days) after nail clearing treatment include: weakness, neck swelling and throat discomfort, dry mouth and even swollen salivary glands, altered taste, nasolacrimal duct obstruction, upper abdominal discomfort and even nausea, and urinary tract damage. Most of the above symptoms appear within 1-5 days of nail clearing treatment and often resolve on their own without special treatment. Some studies have shown that radiation damage to the salivary glands can be reduced by using measures such as taking acidic candy, chewing sugar-free gum, massaging the salivary glands or rehydration during the 131I treatment period [77,78]. However, a recent prospective, randomized, double-blind, controlled study reported that vitamin C contained at different times after the use of 131I did not significantly alter the radiation absorption dose to the salivary glands. Measures such as drinking plenty of water, urinating more often and taking laxatives may help to reduce radiation damage to the abdominal and pelvic cavities, but the possibility of triggering electrolyte disturbances needs to be noted. In patients with combined other chronic diseases and/or advanced DTC, persistent hypothyroidism combined with damage from 131I after nail clearance, the underlying disease condition may worsen in the short term and needs to be closely observed and promptly managed. In addition, patients may experience some psychological changes such as boredom, anxiety, insomnia, fear, etc. in the short term after nail clearing treatment, which is not a direct damage of 131I but originates from some factors during the treatment implementation (e.g. radiation protection isolation, gradual aggravation of hypothyroidism and other disease effects, etc.).
Thyroid hormone therapy after 131I nail clearing treatment
If more thyroid tissue remains before the treatment, the start of L-T4 treatment may be delayed and the dose of L-T4 supplementation should be increased gradually because the 131I used for thyroid clearance destroys the thyroid tissue and releases thyroid hormones into the blood to varying degrees.
Indications for re-treatment with 131I
In some patients, the residual thyroid gland cannot be completely removed by a single nail cleansing treatment. This is usually due to a large amount of residual thyroid tissue before nail clearing treatment, or inadequate uptake of 131I by residual thyroid tissue and DTC lesions (mostly due to the presence of a large amount of stable iodine in the body), or insufficient 131I dose used for nail clearing, or low sensitivity to 131I radiation. After 4-6 months of nail clearing treatment, an assessment of the completeness of nail clearing can be performed. If no thyroid tissue is visualized in the Dx-WBS images after TSH stimulation and the thyroid aspiration rate of 131I is <1%, it indicates complete 131I nail clearing. Serum Tg testing and thyroid ultrasonography may also assist in determining whether nail clearance is complete.
If there is still residual thyroid tissue after the first thyroid clearance, re-cleaning treatment can be performed to achieve the goal of complete thyroid clearance. The principles of 131I dose determination are the same as for the first treatment. However, some investigators believe that if no abnormal extra-thyroidal 131I uptake is seen on Rx-WBS after the first nail clearing in such patients, if serum Tg is continuously monitored at <1ng/mL on dynamic monitoring, and if there are no significant abnormalities on neck ultrasound, re-clearing is not necessary.
Indications for 131I focal clearance therapy
131I focal clearance is indicated for DTC metastases (including local lymph node metastases and distant metastases) that cannot be surgically removed but have iodine uptake. The aim of treatment is to remove the lesion or partially relieve the disease. The efficacy of focal clearance therapy is directly related to the extent of 131I uptake by the metastases and the retention time of 131I in the lesions, and is also influenced by the patient’s age, the size and location of the metastases, and the radiosensitivity of the lesions to 131I. Younger patients have a higher likelihood of obtaining a cure, and small metastases in soft tissues and lungs are easily cleared; metastases that have formed substantial masses or bone metastases with combined bone destruction are often poorly treated with focal clearance, even if the lesions clearly take up 131I. Advanced age, concomitant other serious diseases or those who cannot tolerate pre-treatment hypothyroidism should not be treated with 131I clearance. Metastases located at critical sites (e.g. intracranial or paraspinal, intra-airway, paragonimally gonadal metastases, etc.), if inoperable, are not suitable for 131I focal clearance therapy even if the lesion significantly uptakes 131I, and should be treated by other methods.
Implementation and follow-up of 131I focal clearance therapy
The first 131I focal clearance treatment should be performed at least 3 months after 131I nail clearance. The dose of 131I for a single focal clearance treatment is controversial. The empirical dose is 3.7-7.4 GBq (100-200 mCi). There are two other methods of determining the treatment dose: dose calculation based on the upper limit of radiation tolerance of the blood and the whole body, and dose calculation based on the amount of radiation required for the tumor lesion. There are no prospective studies on which of these three methods is the best. The management of the perifocal treatment period is basically the same as that of nail clearing treatment. 131I clearing treatment is followed by Rx-WBS 2-10 days later to predict the treatment effect and the need for subsequent clearing treatment.
After 6 months of focal clearance treatment, an efficacy assessment can be performed. If the treatment is effective (sustained decrease in serum Tg and reduction of metastases on imaging), repeat focal clearance treatment with an interval of 4-8 months between focal clearance treatments is recommended. If the serum Tg continues to rise after focal clearance treatment, or if imaging shows an increase in metastases, or if 18F-FDG PET reveals additional hypermetabolic lesions, this indicates that the treatment has no significant effect and termination of 131I treatment should be considered.
Maximum dose and safety of repeated 131I therapy
131I therapy is a relatively safe treatment. To date, it has not been possible to determine the upper limit of 131I treatment dose (both single dose and cumulative dose) through prospective clinical studies. However, retrospective statistical analysis suggests that the risk of radiation side effects increases with the number of 131I treatments and the cumulative 131I dose. The more common side effects include chronic salivary gland injury, dental caries, nasolacrimal duct obstruction, or gastrointestinal reactions. 131I treatment rarely causes bone marrow suppression and renal function abnormalities, which can be detected promptly by monitoring blood and renal function before and after treatment. there is no consistent conclusion on the relationship between 131I treatment and secondary tumors. There is insufficient evidence that 131I treatment affects the reproductive system, but women are advised to avoid pregnancy for 6-12 months after 131I treatment.
Patients with DTC treated with 131I after surgery are considered to be “clinically cured” if they meet the following criteria.
1. There is no clinical evidence of tumor presence.
2. No imaging evidence of tumor presence.
3. No uptake of 131I by the thyroid bed and extra-bed tissue is detected by Rx-WBS after nail clearing treatment.
4, Serum Tg was not measured in the TSH suppressed state and after TSH stimulation in the absence of TgAb interference (generally Tg<1ng/mL).
Adjuvant external irradiation therapy or chemotherapy for DTC
After surgery and 131I treatment for invasive DTC, the role of external irradiation therapy in reducing the recurrence rate is unclear and is not recommended for routine use. External irradiation therapy may be considered in the following cases.
1, for the purpose of local palliative treatment.
2, with residual tumors visible to the naked eye that cannot be treated with surgery or 131I.
3.painful bone metastases.
4.Located in critical areas and inoperable for surgery or 131I treatment (e.g. spinal metastasis, central nervous system metastasis, certain mediastinal or inferior ramus lymph node metastasis, pelvic metastasis, etc.).
DTC is not sensitive to chemotherapeutic agents. Chemotherapy is only used as palliative treatment or as an attempted treatment after other means have failed. Doxorubicin (Adriamycin) is the only drug approved by the FDA for metastatic thyroid cancer and is more effective for pulmonary metastases than for bone or lymph node metastases.
Why is long-term follow-up needed for patients with DTC?
Although most DTC patients have a good prognosis and low mortality rate, about 30% of DTC patients will develop recurrence or metastasis, 2/3 of which occur within 10 years after surgery, and those with postoperative recurrence and distant metastasis have a poor prognosis. The purpose of long-term follow-up of DTC patients is to.
1. to monitor those who are clinically cured for early detection of recurrent tumors and metastases
2.For those with recurrent DTC or surviving with tumor, to dynamically observe the progress of disease and treatment effect and adjust the treatment plan.
3.Monitoring the effect of TSH inhibition therapy.
4.Dynamic observation of the condition of certain concomitant diseases (such as heart disease, other malignant tumors, etc.) in patients with DTC.
Tg cut-point values suggestive of disease-free survival in patients with DTC who have had their entire thyroid gland cleared. It is generally accepted that the Tg cut point value for disease free survival in DTC patients with TSH suppression after surgery and 131I thyroid clearance is 1ng/mL, however, there is considerable controversy regarding the serum Tg cut point value after TSH stimulation that predicts residual or recurrent DTC tumors. The available evidence suggests that Tg >2ng/mL after TSH stimulation (TSH >30mU/L) may be a highly sensitive indicator of the presence of cancer cells, with a positive predictive value of almost 100% and a high negative predictive value. If the Tg cut-point value after TSH stimulation is reduced to 1ng/mL, the positive predictive value is about 85%; when it is reduced to 0.5ng/mL, the positive predictive value is further reduced, but the negative predictive value can be as high as 98%.
Other elements included in the long-term follow-up of DTC
Long-term safety of 131I therapy: including effects on secondary tumors, reproductive system. However, over-screening and screening should be avoided.
Effectiveness of TSH suppression therapy: including whether TSH suppression therapy is achieved, and side effects of therapy.
Concomitant diseases of DTC patients: Since the clinical urgency of certain concomitant diseases (e.g. heart disease, other malignant tumors, etc.) may be higher than that of DTC itself, the disease of the above concomitant diseases should also be dynamically observed during long-term follow-up.
Management of recurrence or metastasis of DTC
The recurrence or metastasis found during the follow-up period may be a residual DTC lesion after the original treatment, or it may be a reoccurrence of the disease progression of a previously cured DTC. Local recurrence or metastasis may occur in residual thyroid tissue, soft tissue of the neck and lymph nodes, while distant metastasis may occur in the lung, bone, brain and bone marrow. The treatment options for recurrent or metastatic lesions are, in order of priority: surgical resection (for those who may be cured by surgery), 131I therapy (for those whose lesions are amenable to iodine uptake), external radiation therapy, observation in the presence of TSH suppression therapy (for those whose tumors do not progress or progress slowly and are asymptomatic and without involvement of important areas such as the central nervous system), chemotherapy and novel targeted drug therapy (for those with rapidly progressing disease). refractory DTC patients). Exceptionally, new targeted drug therapy may precede external radiation therapy. The final treatment plan must take into account the patient’s general status, co-morbidities and previous response to treatment.
Some patients with completely cleared thyroid DTC have persistently elevated serum Tg levels (>10ng/mL) at follow-up, but no lesions are detected on imaging. In such patients, 3.7-7.4 GBq (100-200 mCi) 131I therapy can be given empirically [124]; if DTC lesions or reduced serum Tg levels are detected by Rx-WBS after treatment, 131I therapy can be repeated; otherwise, 131I therapy should be discontinued and TSH suppression therapy should be the mainstay.
Patients with DTC who develop distant metastases have a reduced overall survival rate, but individual prognosis depends on multiple factors such as the histological characteristics of the primary site, the number, size and distribution of metastases (e.g., brain, bone marrow, lung), age at the time of metastasis diagnosis, affinity of metastases for 18F-FDG and 131I, and response to therapy. Even if survival is not improved, certain therapies may still significantly relieve symptoms or delay progression.