Etiology Most of the cases are based on simple diffuse goiter, and the repeated progression of the disease leads to the transformation of the follicular epithelium from diffuse hyperplasia to focal hyperplasia and degenerative changes in some areas, and finally, due to the repeated alternation of proliferative and degenerative lesions over a long period of time, nodules of different stages of development appear in the gland. The lesion is actually a late manifestation of simple goiter. In patients with nodular goiter, 5% to 8% of them may develop toxic symptoms, known as Plummer’s disease or toxic nodular goiter. Some nodular goiters, by overgrowth of epithelial cells, can form embryonal adenomas or papillary adenocarcinomas, or thyroid cancer. Clinical manifestations 1. The patient has a long history of simple goiter. The age of onset is usually older than 30 years. There are more women than men. The enlargement of the thyroid gland varies in degree and is mostly asymmetric. The number and size of nodules vary, usually multiple nodules, but there may be only one nodule in the early stage. The nodules are soft or slightly hard, smooth, and not painful to the touch. Sometimes the nodules are not well-defined, and touching the surface of the thyroid gland only gives an irregular or lobulated sensation. The disease progresses slowly and most patients are asymptomatic. Larger nodular goiters may cause pressure symptoms such as dyspnea, dysphagia and hoarseness. Acute bleeding within the nodule may result in a sudden increase in size and pain. When hyperthyroidism (Plummer’s disease) occurs in nodular goiter, patients have symptoms such as fatigue, weight loss, palpitations, arrhythmia, fear of heat and sweating, and agitation, but there is no local vascular murmur and tremor in the thyroid gland. Symptoms are often atypical in elderly patients. 3. The patient has a history of radiation, oral medication and family history, and whether the patient comes from a region where endemic goiter is endemic. In general, patients with a long history of nodular goiter, no pressure symptoms, and no symptoms of hyperthyroidism are often unconcerned and come to the clinic for examination when they unintentionally find a thyroid nodule. 4. If the nodule is a hot nodule, also known as a toxic nodule, the patient is mostly 40 to 50 years old or older, the nodule is moderately hard, there are symptoms of hyperthyroidism, and even atrial fibrillation and other arrhythmic manifestations, and if there is bleeding, there can be pain and even fever. In case of larger nodules, compression symptoms may occur, such as dysphonia, dyspnea, chest tightness, shortness of breath and irritating cough. 5. Patients with nodular goiter from iodine deficient areas may have low thyroid function, slowed heart rate, edema, rough skin and anemia. A small number of patients may become cancerous. Warm nodules are more common and can be treated with thyroid preparations, and the enlarged gland can be reduced in size. Cold nodules are less common, and those with clinical hypothyroidism can be treated with thyroid preparations, but often require surgery. 1. Ultrasound of the thyroid gland Clinical ultrasound of the thyroid gland can clarify whether a thyroid nodule is substantial or cystic in nature, with a 95% diagnostic rate. Most thyroid nodules with cysts are benign nodules and can be cured by aspiration or reduced in size. Those with parenchymal nodules should also have a thyroid scan or puncture for pathology, etc. Ultrasound image examination with high resolution can analyze nodules down to 1mm lesions. Those clinically considered single nodules can often be found to be multinodular, close to what is seen at autopsy. Most cystic lesions are not truly cystic, but are lesions with solid tissue and can show mixed echogenic clusters. 2, radionuclide imaging commonly used thyroid scans are nuclear [131] Ⅰ and 99mTc that is [131] iodine scan [99] technetium scan. Thyroid nodules are classified by their different uptake of iodine and different images. 99mTc can be taken up by the thyroid gland like iodine but cannot be converted. Malignant nodules cannot take up iodine, and the malignant area will appear as a radiologically sparse area. According to their iodine uptake ability, they can be classified as non-functional cold nodules, normal functioning warm nodules and high functioning hot nodules. The disadvantage of radionuclide or 99mTc scan is that it cannot completely distinguish benign or malignant nodules, but is only a preliminary judgment analysis. There is a report of 22 patients with radionuclide scans, regardless of their thyroid function, all of whom underwent surgery, resulting in 84% cold nodules, 10.5% warm nodules and 5.5% hot nodules, of which 16% of cold nodules, 9% of warm nodules and 4% of hot nodules were malignant. The malignancy of hot nodules is small, but there are also malignant nodular lesions among them. In recent years, a positive phase scan of the thyroid gland applying 75 selenium-selenomethionine as a tracer was also carried out, which showed more cell divisions and higher cell density within the malignant nodular lesions compared with normal thyroid tissue, and positive phase images appeared at the lesions. Those who were cold nodules by [131]Ⅰ or 99mTc scan and positive phase image by 75 selenium-selenomethionine scan had more than 50% possibility of malignant nodular lesions. The application of Americium-241 fluorescence scanning technique can identify benign nodules from malignant nodules by indirect measurement of iodine volume, which is more sensitive and effective than [131]Ⅰ and 99mTc scans, but false positives also occur. In addition, there are also examination methods with MRI, dry plate radiography, electron radiographs and temperature recorders, all of which need to be further applied. 3, thyroid puncture histopathological examination The application of fine needle needle aspiration biopsy examination, for the diagnosis of thyroid nodules has a certain value, relatively safe. The results of the puncture can help to indicate surgical treatment, and its cytological accuracy is 50% to 97%. However, there can be sampling errors, especially in patients with cystic changes and in those with smaller nodules, such as lesions smaller than 1 cm, where puncture accuracy can be difficult. If fine needle biopsy cannot be determined, coarse needle re-puncture biopsy can also be used, and the results may be more accurate. However, after the puncture needle enters the malignant nodal cancer, it can spread the cancer cells as its harmful effects and special attention should be paid. In order to clarify the nature of nodules before surgery, open thyroid tissue biopsy may also be used for comprehensive analysis. Some of them have endocrine function, which is clinically called nodular hyperthyroidism, while others have no endocrine function, which is general nodular goiter, and some are hypofunctional, which should be considered as possible thyroid tumor. The diagnosis of simple nodular goiter is generally not difficult, with a long medical history, mostly without pressure symptoms, and generally normal clinical manifestations, and its thyroid tissue can shrink to varying degrees when treated with thyroid preparations. The final diagnosis should rely on pathological examination to clarify the nature of the thyroid nodule. Treatment Generally, simple nodular goiter, whether single or multiple nodules, can be treated with thyroid preparations if they are warm or cold nodules. Give thyroid powder (tablets), divided into 1 or 2 oral doses per day. Or just use levothyroxine sodium (L-T4) tablets, divided into 1 or 2 times a day. Those whose enlarged nodules shrink after treatment can continue to use until they disappear completely. Those whose nodules do not disappear after treatment should be treated by removal of thyroid nodules, and changes in thyroid function should be observed during treatment. For hot nodules with functional autonomy, surgical treatment should also be the main treatment, and postoperative changes in thyroid function should also be observed. A few of the cold nodules are thyroid dysplasia, which can be treated with thyroid preparations for 4-6 months. If the nodules shrink, surgery can be avoided; if the nodules do not shrink, but grow rapidly and involve the surrounding tissues, they should be considered malignant carcinomas, and surgical treatment should be sought as soon as possible. Surgical treatment is often a complete clearance, and postoperative hypothyroidism often occurs, which must be treated with lifelong thyroid hormone replacement.