Introduction

The thyroid is a small butterfly-shaped gland inside the neck, located in front of the trachea (windpipe) and below the larynx (voicebox). It produces two thyroid hormones - tri-iodothyronine (T3) and thyroxine (T4) - that travel though the blood to all tissues of the body.Thyroid hormones regulate how the body breaks down food and either uses that energy immediately or stores it for the future. In other words, our thyroid hormones regulate our body's metabolism.¹

Diseases of the thyroid gland are common,and most are of a metabolic or immunologic nature.² Major Thyroid gland abnormalities are Hyperthyroidism, Hypothyroidism, Thyroid Nodules. Other thyroid problems include cancer, thyroiditis (swelling of the thyroid gland), or a goiter, which is an enlargement of the thyroid gland.¹

The spectrum of thyroid cancers ranges from one of the most indolent to one of the most aggressive solid tumors identified. Conventional therapies for thyroid cancers are based on the histologic type of thyroid cancers such as papillary or follicular thyroid cancer (differentiated thyroid cancer (DTC)), medullary thyroid cancer (MTC), or anaplastic thyroid cancer (ATC).³

While surgery is one of the key treatments for all such types of thyroid cancers, additional therapies vary .Effective targeted therapy for DTC is a decades-old practice with systemic therapies of thyroid stimulating hormone suppression and radioactive iodine therapy. Recent advances in understanding pathogenesis of DTC and development of molecular targeted therapy have dramatically transformed the field of clinical research in thyroid cancer.⁴

Treatment of benign hyperthyroidism has shown that functional imaging is essentially linked to therapy and uptake of iodine-131 ((131)I) cannot be assumed but should be tested by pre-imaging with radio-isotopes as 10% of patients may not be suitable for (131)I therapy and 1% may have a co-existent cancer.³

Medullary thyroid carcinoma (MTC) originates in the thyroid C cells, accounting for 5% to 10% or all thyroid malignancies. Mutations of the RET proto-oncogene have been identified in the germline DNA of patients with familial MTC syndromes. Genetic testing can identify patients affected by multiple endocrine neoplasia types IIA and IIB and familial MTC, allowing early diagnosis and possible cure. Surgical treatment is total thyroidectomy. Plasma calcitonin measurements are excellent markers for postoperative follow-up. Adjunctive therapy includes radiotherapy and chemotherapy. The overall prognosis is worse than papillary thyroid carcinoma. Recent advances in genetic testing allow early diagnosis and treatment of familial MTC syndromes.⁵

Differentiated thyroid cancer remains unique in that it is almost alone among common solid tumors in that it is routinely cured even if cannot all be removed by surgery. It involve trearment with cheap isotope preparation; (131)I. However, in some differentiated thyroid cancers there is no accumulation of (131)I and we know this is due to the loss, or down regulation of the sodium iodide symporter gene. This has led to the development of several strategies, for example with the use of lithium or retinoids or gene treatment.³

Another approach has been the idea of using radiolabeled somatostatin analogs, which are able to demonstrate uptake in the tumor and, more recently, beta-emitting isotopes have been used for therapy when other options have failed.³ Somatostatinreceptors have been identified on many cells of neuroendocrine origin, including the thyroid C cells. Scintigraphy with indium-lll-labeled octreotide is a recent radionuclide imaging method based on the knowledge that metastatic MTC may contain somatostatin receptors.⁵

Multiple endocrine neoplasia IIa and IIb and familial medullary thyroid carcinoma are inherited conditions with autosomal dominance and incomplete penetrance. Traditionally, diagnosis and screening for these conditions have been done using pentagastrin stimulation tests and plasma calcitonin determinations. Recent genetic mapping, however, has assigned the genes responsible for these tumors to the pericentromeric region of chromosome 10. Available data suggest that mutations in exon 10, 11, or 16 of the RET proto-oncogene are responsible for MEN IIa and IIb and familial non-MEN medullary thyroid carcinoma. Thus, genetic testing can identify affected members of a kindred and will probably lead to early thyroidectomy and possible cure for gene carriers.⁶

Recent linkage of the gene for multiple endocrine neoplasia type 2A and 2B to the centromeric region of chromosome 10 has provided new insight into the causes of medullary thyroid carcinoma and has provided tools to diagnose gene carriers status for this syndrome with greater than 90% certainty.⁷

References

1. http://www.nlm.nih.gov/medlineplus/thyroiddiseases.html
2. Samuel A. Wells, Jr. Recent Advances in theTreatment of Thyroid Carcinoma
3. Buscombe J, Hirji H, Witney-Smith C.Nuclear medicine in the management of thyroid disease. Expert Rev Anticancer Ther. 2008 Sep;8(9):1425-31.
4. Jennifer A Woyach1 and Manisha H Shah1,2 New therapeutic advances in themanagement of progressive thyroid cancer
5. Dario Giuffrida1 & Hossein Gharib2.Current diagnosis and management of medullary thyroid carcinoma. Annals of Oncology 9: 695-701, 1998
6. Ledger GA, Khosla S, Lindor NM, Thibodeau SN, Gharib HGenetic testing in the diagnosis and management of multiple endocrine neoplasia type II.
Ann Intern Med. 1995 Jan 15;122(2):118-24.
7. Grauer A, Raue F, Gagel RF.Changing concepts in the management of hereditary and sporadic medullary thyroid carcinoma.
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