Thyroid nodule overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Thyroid nodules have been defined by the American Thyroid Association (ATA) as “discrete lesions within the thyroid gland, radiologically distinct from surrounding thyroid parenchyma.”
Historical Perspective
In 1500, a renowned artist named Leonardo da Vinci was the first who recognized and drew the thyroid gland. In 1834, Robert Graves was the first who described a syndrome of palpitation, goiter, and exophthalmos. In 1857, Maurice Schiff was the first to perform successful total thyroidectomies in animals. In 1895, Adolf Magnus Levy was the first to describe the influence of the thyroid gland and thyroid hormones on the basal metabolic rate. In 1947, Cope, Rawson, and McArthur were the first who described the usage of radioactive iodine for demonstration of a "hot" thyroid nodule. In 1948, T. Templa, J. Aleksandrowicz, and M. Till were the first who described the usage of fine needle thyroid biopsy as a diagnostic method for thyroid nodules.
Classification
There are various methods for classifying a thyroid nodule. A method has been developed by the National Cancer Institute (NCI) to address terminology and other issues related to thyroid fine-needle aspiration (FNA), called "The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)". The other classification method is the TNM classification (tumor-node-metastasis) method developed by the American Joint Committee on Cancer and the International Union against Cancer focused on prognosis has been established to avoid heterogeneity of prognostic classification schemes used for differentiated thyroid cancers. Thyroid nodules may also be classified based on their ultrasound properties according to the TIRAD classification method, which has been proposed by Horvath et al, with a modified recommendation from Jin Kwak et al, and finally, thyroid nodules may also be classified on the basis of origin.
Pathophysiology
Thyroid nodules may arise from different cells in the thyroid parenchyma. The pathogenesis of a thyroid nodule may differ based on the type of the nodule, and whether it is malignant or benign. Basically thyroid nodules may develop secondary to hyperplasia, mutations and resultant carcinoma, excess colloid accumulation, or from inflammation of thyroid tissue. Genetic mutation is considered as one of the most important mechanisms of developing thyroid nodules, especially neoplastic thyroid nodules. Most of these mutations occur as somatic mutations, while some may exhibit familial inheritance. The most important variety of familial thyroid cancers are caused by genetic mutations, and are called familial non-medullary thyroid cancer (FNMTC). Other important genes related to thyroid nodule formation include, N&H, RAS, RET, Gsp, C-MET, TRK, EGF / EGF-R, and P53.
Causes
The major causes of thyroid nodule development include, multinodular (sporadic) goiter, Hashimoto's thyroiditis, cysts, macrofollicular/microfollicular adenomas, childhood radioiodine exposure, familial history, and gene mutations include N&H ras, RET, Gsp, C-MET (α and β subunit), TRK, EGF / EGF-R, and P53 mutation.
Differentiating Thyroid Nodule From Other Diseases
Neck masses can be mistaken with thyroid nodules. The most important neck masses that can be mistaken with thyroid nodules include: Thyroglossal duct cyst, parathyroid cancer, parathyroid cyst, and branchial cleft cyst. While the diagnosis of a thyroid nodule is established, thyroid nodule should be differentiated based on benign or malignant features and the type of nodule.
Epidemiology and Demographics
Worldwide, the incidence of thyroid nodule ranges from as low of 40,000 per 100,000 persons to a high of 71,000 per 100,000 persons with an average incidence of 50,000 per 100,000 persons. The incidence of thyroid cancer is estimated to be a total number of 48,288 cases annually in United states. Thyroid nodules are common, their prevalence being largely dependent on the identification method, as sensitivity and specificity of different methods for thyroid nodule diagnosis varies. In United States, the prevalence of thyroid nodule detected by palpation alone ranges from a low of 2,000 per 100,000 persons to a high of 6,000 per 100,000 persons, while the prevalence of thyroid nodule detected by ultrasound ranges from a low of 20,000 per 100,000 persons to a high of 35,000 per 100,000 persons. Worldwide, the prevalence of palpable thyroid nodule is approximately 5,000 per 100,000 in women and 1,000 per 100,000 in men living in iodine-sufficient parts of the world, and the prevalence of ultrasound detected thyroid nodules ranges from as low as 19,000 per 100,000 to as high as 68,000 per 100,000. Thyroid nodules commonly affects individuals younger than 20 and older than 50 years of age. Females are more commonly affected with thyroid nodules than males.
Risk Factors
Common risk factors associated with thyroid nodules include: Older age, iodine deficiency, previous history of iodine deficiency and hypothyroidism, living in iodine deficient areas, family history of autoimmune diseases, multiparity, and smoking.
Screening
According to USPSTF, screening for thyroid cancer is not recommended and there is insufficient evidence to recommend routine screening for thyroid nodule.
Natural History, Complications and Prognosis
A solitary thyroid nodule may become symptomatic if it grows rapidly due to hemorrhage or malignancies, invades laryngeal nerves, compressing nearby structures, and secretory nodules that produce TSH. Thyroid nodules may be a manifestation of thyroid cancer, that usually develops in the 6th decade of life, and start with symptoms such as weight loss, fatigue, and hoarseness. Without treatment, the patient with benignnodules may remain asymptomatic, while the patients with thyroid neoplasm may develop distant metastasis, which may eventually lead to death. The most common complications of thyroid nodules are hoarseness, horner syndrome, nodule rupture, needle track seeding, hemorrhage/hematoma, dysphagia, upper airway obstruction, pain, skin burn, vasovagal reaction, hypothyroidism, transient thyrotoxicosis, anaphylactic reaction, thromboembolism, and pneumothorax. Benign thyroid nodules have great prognosis, while prognosis of malignant thyroid nodules may be determined based on their type by scoring system of TNM staging.