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Thyroid nodules

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4% of U.S. population between ages 30 and 60.

Thyroid nodules are one of the most common incidental findings on Imaging examinations.

Affects 19-68% of randomly selected individuals.

Each year more than 600,000 thyroid fine needle aspiration biopsies are performed in the United States.

Autopsy studies suggest prevalence of single or multiple nodules in as much as 50% of the population.

Thyroid nodules are found in 67% of thyroid ultrasounds and incidentally found in up to 25% of contrast-enhanced chest CT and 5 to 18% of neck CT and MRI.

Increasing in frequency as they are being identified largely due to growing use of diagnostic imaging.

Nonpalpable thyroid nodules are common and can be detected with ultrasound in 30-50% of the general population.

Palpable nodules increase with age, with a prevalence of approximately 5% in patients 50 years and older.

Nodules are more prevalent at autopsy or surgery or when utilizing ultrasound examinations with 50% of thyroids studied, in such a fashion, having nodules.

Thyroid nodules found incidentally at surgery, ultrasound, or autopsy are almost always benign.

Indeterminate cytology characterized by cytologic or architectural atypos without overt nuclear features of papillary thyroid cancer, is found in 20% fine needle aspiration thyroid nodule biopsies.
Nodules with indeterminate cytology have a 10-40% risk of malignancy.
The management of indeterminate thyroid nodules has expanded from repeat fine needle aspiration, or diagnostic hemithyroidectomy now includes molecular testing.

In 90% of patients with benign molecular test results,  thyroid nodules are managed non-operatively, so more than 25,000 patients per year can avoid diagnostic surgery.

Molecular testing is based on analysis of RNA-based gene expression or detection of somatic mutations.
Presently or nay test uses next generation messenger RNA sequencing.

90% of small, non–palpable, benign lesions that will never become clinically significant tumors.

A thyroid nodule sonographically considered a pure cyst has a negligible malignancy risk with a risk of malignancy of less than 1%.

Partially cystic nodule with no suspicious features are at very low suspicion for malignancy with a risk of less than 3%, and partially cystic nodule with eccentric soid areas have a low suspicion of malignancy of 5-10%.

5-15% of nodules are malignant.

Distinguishing between low risk and high-risk patients requires a thorough history and physical exam, laboratory testing, neck ultrasound, and for appropriately selected patients a fine needle aspiration.

Autonomous functioning thyroid nodules that cause hyperthyroidism should be identified before biopsy to avoid complications and ensure appropriate imaging and treatment.

A radionuclide thyroid scan should be done only in cases with suppressed thyroid stimulating hormone (TSH).

Thyroid nodules linked to increase cancer risk include: a history of thyroid cancer in a 1st degree relative, history of external beam radiation a child or adolescent, male gender, and some endocrine endocrinopathies that include the thyroid.

New thyroid nodules developed at approximately 0.1% per year, beginning early in life.

New thyroid nodules developed at about 2% a year in patients after exposure to head and neck radiation.

Incident increasing because of increased detection of small low, it asymptomatic nodules.

Approximately 23% of solitary nodules are actually dominant nodules within a thyroid containing multiple other non palpable nodules.

Nonpalpable nodules (incidentalomas) should be biopsied only if the nodule is larger than 1 cm, if there is a family history of medullary carcinoma, or if ultrasound findings suggest malignancy.

Benign nodules-respond to thyroid suppression about 50%of the time.

More common in areas with iodine deficiency.

4 times more common in women than men.

In evaluating a thyroid nodule, a thyrotropin level should be measured and if found to be low needs to be pursued as the whether the nodule is hyperfunctioning, suggesting hyperthyroidism and is it an unusual finding in cases of neoplasm.

A purely cystic nodule has a less than 1% risk of malignancy.

Develop at a rate of 2 percent annually in individuals exposed to ionizing radiation.

Most patients are euthyroid with less than 1% of thyroid nodules associated with hyperthyroidism.

Colloid nodules are the most common type of thyroid nodule and are not associated with malignancy.

Thyroid cancer usually presents as a solitary palpable nodule.

Most common malignant thyroid nodule is a papillary cancer.

Thyroid function tests, antithyroid antibodies, thyroglobulin tests are not helpful in determining whether a nodule is benign or malignant.

Nodules 1 cm a larger in diameter prompt diagnostic evaluation.

Cornerstone of thyroid nodule evaluation is fine needle aspiration.

Fine needle aspiration biopsy fastest, easiest and most cost effective method of assessing thyroid nodules.

Thyroid nodule biopsy by fine needle aspiration is the preferred procedure for evaluating suspicious nodules.

Fine needle aspiration biopsy indications include nodule size, ultrasound characteristics and clinical features that might predict risk of malignancy.

Ultrasound guided needle aspirations accurately classify 62-85% of thyroid nodules as benign, avoiding diagnostic surgery.

15-30% of fine needle aspirations have indeterminate cytological findings including atypia of undetermined significance, follicular neoplasm suspicious for follicular neoplasm, and suspicious for malignancy.

Most biopsies with cytology ally indeterminate nodules are referred for diagnostic thyroid surgery, but the majority are proven to have benign disease.

For these patients thyroid surgery would be unnecessary and yet can expose them to 2-10% risk of surgical complications and many would require thyroid replacement therapy for life.

When indeterminate aspirates are analyzed for the presence of the BRAF and RAS mutations and for RET/PTC and PAX8-PPAR gamma gene rearrangements, mutations are found in 16% of cases and can identify malignant nodules.

Suspicious malignant ultrasound characteristics of a thyroid nodule include central hypervascularity, microcalcifications, hypoechogenicity, in distinct, and irregular borders.

The size of the nodule is an independent risk factor, with the size less than 1 cm being unlikely to be cancer and a size of a 4 cm or larger being very likely malignant.

More than 50% of all malignant thyroid nodules are asymptomatic.

The probability that a nodule it is malignant increases when signs or symptoms are present.

The likelihood that a thyroid nodules is malignant increases approximately 7 fold if it is firm, fixed, rapidly growing, associated with regional lymphadenopathy, causing vocal cord paralysis, or if there are symptoms of invasion into surrounding neck structures.

The risk of a thyroid nodules being malignant is higher in patients younger than 15 years and in men.

Thyroid nodule suspicion for malignancy increases with prior head and neck irradiation, a history of disease associated with thyroid cancers such as familial adenomatous polyposis, Carney complex, Cowden’s syndrome, MEN2A or 2B, evidence of thyroid cancer associated diseases or syndromes including hyperparathyroidism, pheochromocytoma, Marfan’s habitussuspicious findings with imaging studies such as PET scan or ultrasound central hypervascularity, irregular borders and/or microcalcifications.

Some encapsulated follicular lesions with partial nuclear features of papillary thyroid carcinoma may present diagnostic dilemma and these lesions represent approximately 10% of all follicular pattern lesions seen at surgical pathology (Arora N).

Fine needle aspiration has a sensitivity and specificity of more than 90% in the evaluation of such nodules.

Fine needle aspiration false-negative rate of 1-11% and false-positive rate of 1-8%.

2-5 five needle aspiration passes are suggested so as to obtain adequate tissue for analysis.

Biopsy of the thyroid nodules is warranted for nodules that are greater than 50% cystic, and for those larger than 2 cm that has a spongiform appearance.

The Bethesda System is used to report cytology analysis.

The Bethesda System categories are: nondiagnostic, with the 20% malignancy risk, benign 2.5% malignancy risk, atypia of undetermined significance, with a 14% malignancy risk, follicular neoplasm with a 25% malignancy risk, suspicious for malignancy with a 70% malignancy risk, and malignant with a 99% malignancy risk.

In some patients with benign nodules it may be symptomatic and treatment includes simple nodule aspiration, minimally invasive techniques, or surgical resection.

Most thyroid nodules are benign and require only serial observation.

Surgery is the main therapeutic approach for large cystic nodules that result in compressive symptoms.

Aspiration of benign cysts have a recurrence rate as high as 60-90%.

Percutaneous injection of ethanol is it a safe alternative to conventional surgery in patients with large benign, symptomatic cystic nodule.

Radiofrequency ablation of benign large predominantly solid thyroid nodules can result in substantial volume reduction, improves compressive symptoms and cosmetic concerns and does not affect normal thyroid function and is a low risk alternative to conventional treatment.

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