Detection of any metastases of thyroid cancer can be performed with a full body scintigraphy using iodine-131.

While the increased serum concentration of calcitonin is not harmful, it is useful as a marker which can be tested in blood.

A second marker, carcinoembryonic antigen (CEA), also produced by medullary thyroid carcinoma, is released into the blood and it is useful as a serum or blood tumor marker. In general, measurement of serum CEA is less sensitive than serum calcitonin for detecting the presence of a tumor, but has less minute to minute variability and is therefore useful as an indicator of tumor mass.

Diagnosis is primarily performed via fine needle aspiration of the lesion of the thyroid to distinguish it from other types of thyroid lesions. Microscopic examination will show amyloid and hyperplasia of parafollicular C cells.

The MACIS system of estimating the prognosis of papillary thyroid cancer was developed by Clive S. Grant at the Mayo Clinic, and was based on careful evaluation of a large group of patients. It is probably the most reliable staging method available.

It assigns scores to the main factors involved, and uses the sum of this score to calculate the prognosis:

Most patients fall into the low-risk category (MACIS score less than 6.0) and are cured of the cancer at the time of surgery.

Children with multiple lung metastases and/or a miliary aspect still have an excellent long-term prognosis if given adequate treatment.

Hurthle cell thyroid cancer is often considered a variant of follicular cell carcinoma. Hurthle cell forms are more likely than follicular carcinomas to be bilateral and multifocal and to metastasize to lymph nodes. Like follicular carcinoma, unilateral hemithyroidectomy is performed for non-invasive disease, and total thyroidectomy for invasive disease.

Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV.

Cancer 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.

Some studies have shown that thyroglobulin (Tg) testing combined with neck ultrasound is more productive in finding disease recurrence than full- or whole-body scans (WBS) using radioactive iodine. However, current protocol (in the USA) suggests a small number of clean annual WBS are required before relying on Tg testing plus neck ultrasound. When needed, whole body scans consist of withdrawal from thyroxine medication and/or injection of recombinant human Thyroid stimulating hormone (TSH). In both cases, a low iodine diet regimen must also be followed to optimize the takeup of the radioactive iodine dose. Low dose radioiodine of a few millicuries is administered. Full body nuclear medicine scan follows using a gamma camera. Scan doses of radioactive iodine may be I or I.

Recombinant human TSH, commercial name Thyrogen, is produced in cell culture from genetically engineered hamster cells.

Fine Needle Aspiration Cytology (FNAC) is a cheap, simple, and safe method in obtaining cytological specimens for diagnosis by using a needle and a syringe. The "Bethesda System for Reporting Thyroid Cytopathology" is the system used to report whether the thyroid cytological specimen is benign or malignant. It can be divided into six categories:

Repeated FNAC is recommended for Category I, followed by clinical follow-up in Category II, repeat FNAC for Category III, and lobectomy for Category IV, near total-thyroidectomy/lobectomy for Category V, and near total thyroidectomy for Category VI. The risk of malignancy in a malignant FNAC report is 93.7% while for suspicious FNAC report, it is 18.9%.

Blood tests may be done prior to or in lieu of a biopsy. The possibility of a nodule which secretes thyroid hormone (which is less likely to be cancer) or hypothyroidism is investigated by measuring thyroid stimulating hormone (TSH), and the thyroid hormones thyroxine (T4) and triiodothyronine (T3).

Tests for serum thyroid autoantibodies are sometimes done as these may indicate autoimmune thyroid disease (which can mimic nodular disease).

The first step in diagnosing a thyroid neoplasm is a physical exam of the neck area. If any abnormalities exist, a doctor needs to be consulted. A family doctor may conduct blood tests, an ultrasound, and nuclear scan as steps to a diagnosis. The results from these tests are then read by an endocrinologist who will determine what problems the thyroid has.

Hyperthyroidism and hypothyroidism are two conditions that often arise from an abnormally functioning thyroid gland. These occur when the thyroid is producing too much or too little thyroid hormone respectively.

Thyroid nodules are a major presentation of thyroid neoplasms, and are diagnosed by ultrasound guided fine needle aspiration (USG/FNA) or frequently by thyroidectomy (surgical removal and subsequent histological examination). FNA is the most cost-effective and accurate method of obtaining a biopsy sample. As thyroid cancer can take up iodine, radioactive iodine is commonly used to treat thyroid carcinomas, followed by TSH suppression by high-dose thyroxine therapy.

Nodules are of particular concern when they are found in those under the age of 20. The presentation of benign nodules at this age is less likely, and thus the potential for malignancy is far greater.

Treatment of a thyroid nodule depends on many things including size of the nodule, age of the patient, the type of thyroid cancer, and whether or not it has spread to other tissues in the body.

If the nodule is benign, patients may receive thyroxine therapy to suppress thyroid-stimulating hormone and should be reevaluated in 6 months. However, if the benign nodule is inhibiting the patient's normal functions of life; such as breathing, speaking, or swallowing, the thyroid may need to be removed.

Sometimes only part of the thyroid is removed in an attempt to avoid causing hypothyroidism. There's still a risk of hypothyroidism though, as the remaining thyroid tissue may not be able to produce enough hormones in the long-run.

If the nodule is malignant or has indeterminate cytologic features, it may require surgery. A thyroidectomy is a medium risk surgery that can result complications if not performed correctly. Problems with the voice, nerve or muscular damage, or bleeding from a lacerated blood vessel are rare but serious complications that may occur. After removing the thyroid, the patient must be supplied with a replacement hormone for the rest of their life. This is commonly a daily oral medication prescribed by their endocrinologist.

Radioactive iodine-131 is used in patients with papillary or follicular thyroid cancer for ablation of residual thyroid tissue after surgery and for the treatment of thyroid cancer. Patients with medullary, anaplastic, and most Hurthle cell cancers do not benefit from this therapy. External irradiation may be used when the cancer is unresectable, when it recurs after resection, or to relieve pain from bone metastasis.

Parathyroid carcinoma is sometimes diagnosed during surgery for primary hyperparathyroidism. If the surgeon suspects carcinoma based on severity or invasion of surrounding tissues by a firm parathyroid tumor, aggressive excision is performed, including the thyroid and surrounding tissues as necessary.

Agents such as calcimimetics (for example, cinacalcet) are used to mimic calcium and are able to activate the parathyroid calcium-sensing receptor (making the parathyroid gland "think" we have more calcium than we actually do), therefore lowering the calcium level, in an attempt to decrease the hypercalcemia.

A non-minimally invasive Hürthle cell carcinoma is typically treated by a total thyroidectomy followed by radioactive iodine therapy. A Hürthle cell adenoma or a minimally invasive tumor can be treated by a thyroid lobectomy, although some surgeons will perform a total thyroidectomy to prevent the tumor from reappearing and metastasizing.

A modified radical neck dissection may be performed for clinically positive lymph nodes.

Hürthle cell adenomas are most likely diagnosed much more frequently than Hürthle cell carcinomas. The female to male ratio for Hurthle cell adenomas is 8:1, while the ratio is 2:1 for the malignant version. Hürthle cell cancer tends to occur in older patients. The median age at diagnosis for Hürthle cell carcinomas is approximately 61 years old. Typically a painless thyroid mass is found in patients with this type of cancer. As expected, patients with carcinoma usually present larger tumors than patients with adenoma. Rarely, the cancer can spread to the lymph nodes. On few occasions, patients with Hürthle cell carcinoma have distant metastases in the lungs or surrounding bones. Hürthle cell neoplasms are somewhat difficult to differentiate between being benign or malignant. Since the size and growth pattern of the tumor cannot be used to determine malignancy, although larger tumors have higher incidence of malignancy, Hürthle cell adenomas and carcinomas have to be separated by the presence, in the case of carcinomas, or absence, in the case of adenomas, of both capsular invasion and vascular invasion. Tumors displaying only capsular invasion tend to behave less aggressively than those with vascular invasion. Hürthle cell carcinomas are characterized as either minimally invasive or widely invasive tumors. While the minimally invasive or encapsulated carcinoma is fully surrounded by a fibrous capsule, the widely invasive carcinoma shows extensive area of both capsular and vascular invasion with the leftover capsule typically difficult to identify. Classification is important since widely invasive tumors can have outcomes with a 55% mortality rate.

Parathyroid cancer occurs in midlife at the same rate in men and women.

Conditions that appear to result in an increased risk of parathyroid cancer include multiple endocrine neoplasia type 1, autosomal dominant familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome (which also is hereditary). Parathyroid cancer has also been associated with external radiation exposure, but, most reports describe an association between radiation and the more common parathyroid adenoma.

Management of MEN2 patients includes thyroidectomy including cervical central and bilateral lymph nodes dissection for MTC, unilateral adrenalectomy for unilateral pheochromocytoma or bilateral adrenalectomy when both glands are involved and selective resection of pathologic parathyroid glands for primary hyperparathyroidism.

Familial genetic screening is recommended to identify at risk subjects who will develop the disease, permitting early management by performing prophylactic thyroidectomy, giving them the best chance of cure.

Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC indicating the necessity of a complete thyroid surgery for index cases with MTC and the early thyroidectomy for screened at risk subjects.

There are three main treatments for Hürthle cell adenomas. Once the adenoma is detected most often the nodules removed to prevent the cells from later metastisizing. A total thyroidectomy is often performed, this results in a complete removal of the thyroid. Some patients may only have half of their thyroid removed, this is known as a thyroid lobectomy. Another treatment option includes pharmacological suppression of thyroid hormone. The thyroid gland is responsible for producing the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Patients with suppressed thyroid function often require oral thyroid replacement (e.g. levothyroxine) in order to maintain normal thyroid hormone levels. The final treatment option is RAI abaltion (radioactive iodine ablation). This treatment option is used to destroy infected thyroid cells after total thyroidectomy. This treatment does not change prognosis of disease, but will diminish the recurrence rate. Also, Hürthle cells do not respond well to RAI. However, often doctors suggest this treatment to patients with Hürthle cell adenoma and Hürthle cell carcinoma because some Hürthle cells will respond and it will kill remaining tissue.

Autoantibodies to the thyroid gland may be detected in various disease states. There are several anti-thyroid antibodies, including anti-thyroglobulin antibodies (TgAb), anti-microsomal/anti-thyroid peroxidase antibodies (TPOAb), and TSH receptor antibodies (TSHRAb).

- Elevated anti-thryoglobulin (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) can be found in patients with Hashimoto's thyroiditis, the most common autoimmune type of hypothyroidism. TPOAb levels have also been found to be elevated in patients who present with subclinical hypothyroidism (where TSH is elevated, but free T4 is normal), and can help predict progression to overt hypothyroidism. The American Association Thyroid Association thus recommends measuring TPOAb levels when evaluating subclinical hypothyroidism or when trying to identify whether nodular thyroid disease is due to autoimmune thyroid disease.

- When the etiology of hyperthyroidism is not clear after initial clinical and biochemical evaluation, measurement of TSH receptor antibodies (TSHRAb) can help make the diagnosis. In Grave's disease, TSHRAb levels are elevated as they are responsible for activating the TSH receptor and causing increased thyroid hormone production.

A medical biopsy refers to the obtaining of a tissue sample for examination under the microscope or other testing, usually to distinguish cancer from noncancerous conditions. Thyroid tissue may be obtained for biopsy by fine needle aspiration (FNA) or by surgery.

Fine needle aspiration has the advantage of being a brief, safe, outpatient procedure that is safer and less expensive than surgery and does not leave a visible scar. Needle biopsies became widely used in the 1980s, but it was recognized that the accuracy of identification of cancer was good, but not perfect. The accuracy of the diagnosis depends on obtaining tissue from all of the suspicious areas of an abnormal thyroid gland. The reliability of fine needle aspiration is increased when sampling can be guided by ultrasound, and over the last 15 years, this has become the preferred method for thyroid biopsy in North America.

Unlike its differentiated counterparts, anaplastic thyroid cancer is highly unlikely to be curable either by surgery or by any other treatment modality, and is in fact usually unresectable due to its high propensity for invading surrounding tissues.

Palliative treatment consists of radiation therapy usually combined with chemotherapy.

New drugs, such as fosbretabulin (a type of combretastatin), bortezomib and TNF-Related Apoptosis Induced Ligand (TRAIL), are however being under investigation "in vitro" and in human clinical studies. Based on encouraging Phase I and II clinical trial results with fosbretabulin, a type of drug that selectively destroys tumor blood vessels, a large, multi-national clinical trial is being undertaken to determine whether the drug can extend the survival of patients with ATC.

Before gene testing was available, the type and location of tumors determined which type of MEN2 a person had. Gene testing now allows a diagnosis before tumors or symptoms develop.

A table in the multiple endocrine neoplasia article compares the various MEN syndromes. MEN2 and MEN1 are distinct conditions, despite their similar names. MEN2 includes MEN2A, MEN2B and familial medullary thyroid cancer (FMTC).

The common feature among the three sub-types of MEN2 is a high propensity to develop medullary thyroid carcinoma.

Hürthle cell adenoma is the benign analogue of Hürthle cell carcinoma. This adenoma is extremely rare; when it occurs, it usually occurs in women. Often the adenoma is harmless but is removed after detection because its future course cannot be trusted. This mass can be detected and removed before transformation and metastasis. The tumor is often detected by imaging such as ultrasound. The location and size of the tumor may cause pressure and pain to the patient. But often the tumor goes undetected. After detection, the mass is tested using an invasive fine-needle aspiration biopsy.

The role of external beam radiotherapy (EBRT) in thyroid cancer remains controversial and there is no level I evidence to recommend its use in the setting of differentiated thyroid cancers such as papillary and follicular carcinomas. Anaplastic thyroid carcinomas, however, are histologically distinct from differentiated thyroid cancers and due to the highly aggressive nature of ATC aggressive postoperative radiation and chemotherapy are typically recommended.

The National Comprehensive Cancer Network Clinical Practice Guidelines currently recommend that postoperative radiation and chemotherapy be strongly considered. No published randomised controlled trials have examined the addition of EBRT to standard treatment, namely surgery. Radioactive iodine is typically ineffective in the management of ATC as it is not an iodine-avid cancer.

Imbalances in age, sex, completeness of surgical excision, histological type and stage, between patients receiving and not receiving EBRT, confound retrospective studies. Variability also exists between treatment and non-treatment groups in the use of radio-iodine and post-treatment thyroid stimulating hormone (TSH) suppression and treatment techniques between and within retrospective studies.

Some recent studies have indicated that EBRT may be promising, though the number of patients studies has been small.

Clinical trials for investigational treatments are often considered by healthcare professionals and patients as first-line treatment.

DNA testing is now the preferred method of establishing a diagnosis for MEN 2B, and is thought to be almost 100% sensitive and specific. Gordon et al. reported cases of a difference disease—the "multiple mucosal neuroma syndrome"—having the physical phenotype of MEN2B, but without variations in the RET gene and without malignancy.

MEN2B should be entertained as a diagnosis whenever a person is found to have either medullary thyroid carcinoma or pheochromocytoma. Before DNA testing became available, measurement of serum calcitonin was the most important laboratory test for MEN2B. Calcitonin is produced by the "C" cells of the thyroid, which, because they are always hyperplastic or malignant in MEN2B, produce more calcitonin than normal. Calcitonin levels remain a valuable marker to detect recurrence of medullary thyroid carcinoma after thyroidectomy.

Luxol fast blue staining identifies myelin sheathing of some fibers, and lesional cells react immunohistochemically for S-100 protein, collagen type IV, vimentin, NSE, and neural filaments. More mature lesions will react also for EMA, indicating a certain amount of perineurial differentiation. Early lesions, rich in acid mucopolysaccharides, stain positively with alcian blue. When medullary thyroid cancer is present, levels of the hormone calcitonin are elevated in serum and urine. Under the microscope, tumors may closely resemble traumatic neuroma, but the streaming fascicles of mucosal neuroma are usually more uniform and the intertwining nerves of the traumatic neuroma lack the thick perineurium of the mucosal neuroma. Inflammatory cells are not seen in the stroma and dysplasia is not present in the neural tissues.