Thyroid cancer


Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck, difficulty swallowing or voice changes including hoarseness, or a feeling of something being in the throat due to mass effect from the tumor. However, most cases are asymptomatic. Cancer can also occur in the thyroid after spread from other locations, in which case it is not classified as thyroid cancer.
Risk factors include radiation exposure at a young age, having an enlarged thyroid, family history and obesity. The four main types are papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, and anaplastic thyroid cancer. Diagnosis is often based on ultrasound and fine needle aspiration. Screening people without symptoms and at normal risk for the disease is not recommended.
Treatment options may include surgery, radiation therapy including radioactive iodine, chemotherapy, thyroid hormone, targeted therapy, and watchful waiting. Surgery may involve removing part or all of the thyroid. Five-year survival rates are 98% in the United States.
Globally as of 2015, 3.2 million people have thyroid cancer. In 2012, 298,000 new cases occurred. It most commonly is diagnosed between the ages of 20 and 65. Women are affected more often than men. Those of Asian descent are more commonly affected; with a higher rate of mortality among Filipino females. Rates have increased in the last few decades, which is believed to be due to better detection. In 2015, it resulted in 31,900 deaths.

Signs and symptoms

Most people with thyroid cancer do not have symptoms at the time of diagnosis and thyroid nodules are usually found incidentally on imaging of the neck. Up to 65% of adults have small nodules in their thyroids, but typically under 10% of these nodules are found to be cancerous. Sometimes, the first sign is an enlarged lymph node. Later symptoms that can be present are pain in the anterior region of the neck and changes in voice due to the close proximity of the recurrent laryngeal nerve to the thyroid gland. These nodules and enlarged lymph nodes can also cause swelling in the neck and difficulty swallowing.
Thyroid cancer is usually found in a euthyroid patient, but symptoms of hyperthyroidism or hypothyroidism may be associated with a large or metastatic, well-differentiated tumor. Thyroid nodules are of particular concern when they are found in those under the age of 20. At this age, thyroid nodules are more likely to be malignant than benign.

Causes

Thyroid cancers are thought to be related to a number of environmental and genetic predisposing factors, but significant uncertainty remains regarding their causes.
Environmental exposure to ionising radiation from both natural background sources and artificial sources is suspected to play a significant role, and significantly increased rates of thyroid cancer occur in those exposed to mantlefield radiation for lymphoma, and those exposed to iodine-131 following the Chernobyl, Fukushima, Kyshtym, and Windscale nuclear disasters. Thyroiditis and other thyroid diseases also predispose to thyroid cancer.
Genetic causes include multiple endocrine neoplasia type 2, which markedly increases rates, particularly of the rarer medullary form of the disease. Mutations in the genes for MenA and Men2B in multiple endocrine neoplasia is responsible for 25% of medullary thyroid cancers.
Hyperthyroidism is the overfunctioning of the thyroid gland causing an excessive amount of thyroid hormones to be released. These hormones contribute to one's metabolism, growth, brain development, body temperature, and reproductive function. This condition is also linked to Graves' Disease. A symptom of hyperthyroidism is a change in size of one's thyroid, which is associated with patients who have been found to have thyroid cancer. There is also hypothyroidism, when there is an underfunction of the thyroid gland, which is associated with Hashimoto’s thyroidosis. Hashimoto thyroidosis has a direct connection to an increased risk of thyroid cancer, along with multiple other cancer types.
Family relatives who have an issue with thyroids in their life will likely pass it down to their family. But the thyroid issues may present themselves in different ways. These ways can range from hypothyroidism, hyperthyroidism, Graves' Disease, Hashinoto’s thyroidosis and cancer.
The FDA requires a boxed warning in the package inserts of GLP-1 agonists due to the risk of thyroid C-cell tumors, including medullary thyroid cancer, with a warning that GLP-1 agonists are contraindicated in people with a family or personal history of MTC or multiple endocrine neoplasia type 2. In mice, long-term use of GLP-1 agonists stimulates calcitonin secretion, leading to C-cell hypertrophy and an increased risk of thyroid cancer, but no increased secretion of calcitonin has been observed in humans. A retrospective national cohort study in France found an increased risk of thyroid cancer following 1-3 years of treatment with GLP-1 agonists for diabetes, but this was not observed in randomized control trials, as well as in other large retrospective studies, including one with long-term use of GLP-1 agonists and over 10-years of follow-up. A small study of patients with low-risk thyroid cancer undergoing active surveillance showed that GLP-1RA therapy did not affect tumor growth kinetics.

Diagnosis

After a thyroid nodule is found during a physical examination or incidentially on imaging, a referral to an endocrinologist or a thyroidologist may occur. Most commonly, an ultrasound is performed to confirm the presence of a nodule and assess the status of the whole gland. Various radiological clinical criteria, including the thyroid imaging reporting and data system score, are used to characterize the risk of malignancy. TI-RADS developed by the American College of Radiology guides clinicians in deciding which nodules require fine-needle aspiration cytology and in planning follow-up. Various online tools have been developed to assist in applying these criteria to clinical practice. On ultrasound, nodules that are hypoechogenic, having irregular borders, increased vascularity, calcifications, or being taller than wide on transverse views are associated with malignancy. Biopsy or cytology are required if the ultrasound characteristics suggest malignancy. If ultrasound results are equivocal or unclear, or if the thyroid nodule is small, the nodule can be monitored over time with serial ultrasounds. Ultrasound has a sensitivity of 64-77% and a specificity of 82-90% for the detection of thyroid cancer. Measurement of thyroid stimulating hormone, free and/or total triiodothyronine and thyroxine levels, and antithyroid antibodies will help decide if a functional thyroid disease such as Hashimoto's thyroiditis is present, a known cause of a benign nodular goiter. A thyroid scan, performed often in conjunction with a radioactive iodine uptake test may be used to determine whether a nodule is hyperactive which may help to make a decision whether to perform a biopsy of the nodule. Measurement of calcitonin is necessary to exclude the presence of medullary thyroid cancer. To achieve a definitive diagnosis, a fine needle aspiration cytology test may be performed and reported according to the Bethesda system.
After diagnosis, to understand potential for spread of disease, or for follow up monitoring after surgery, a whole body I-131 or I-123 radioactive iodine scan may be performed.
In adults without symptoms, screening for thyroid cancer is not recommended.

Classification

Thyroid cancers can be classified according to their histopathological characteristics. These variants can be distinguished :
The follicular and papillary types together can be classified as "differentiated thyroid cancer". These types have a more favorable prognosis than the medullary and undifferentiated types.
  • Papillary microcarcinoma is a subset of papillary thyroid cancer defined as a nodule measuring less than or equal to 1 cm. 43% of all thyroid cancers and 50% of new cases of papillary thyroid carcinoma are papillary microcarcinoma. Management strategies for incidental papillary microcarcinoma on ultrasound range from total thyroidectomy with radioactive iodine ablation to lobectomy or observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. Woolner et al. first arbitrarily coined the term "occult papillary carcinoma", in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.

    Staging

is the process of determining the extent of the development of a cancer. The TNM staging system is usually used to classify stages of cancers, but not of the brain. The TNM system is broken into three key factors. The T part stands for the size of the tumor, and has it grown into any other body part near the body. The N is for if the cancer has grown into any lymph nodes nearby. And finally, the M stands for if the cancer has metastasized, and if the cancer has spread to any major organs in the body.
After the TNM system has been determined, the number system is then used to describe the severity of the cancer. The stages range from one to four, typically with stage one being the lowest and least amount of cancer spread, and stage four being the highest with the most amount of cancer spread through the body.
Thyroid cancer staging can be determined by either clinical staging which includes several different tests evaluate the extent of the cancer, or pathological staging which includes surgery.