Nodular disorders of the thyroid gland are relatively common among adults with an overall prevalence of approximately 4-7% in the general population. Most thyroid nodules are non cancer benign nodules, but 5-20% of thyroid nodules may be true cancers.

The prevalence of thyroid nodules within a given population depends on a variety of factors that include age, sex, diet, iodine deficiency, and therapeutic and environmental radiation exposure. Thyroid nodules are found in approximately 1.5% of children and adolescents. They are more common in females, and this predisposition exists throughout all age groups. In fact, palpable nodular disease is 6 times more common in adolescent females compared to males of the same age.

Thyroid nodules are more common in women than in men. Prevalence increases with age. Thyroid nodules are found in 5% of persons in old age (>60 years).

One of the major goals in the evaluation of the solitary thyroid nodule is to find out cancer in nodule or cancerous nodules. Evaluation of solitary thyroid nodules requires the collaboration of thyroid expert, expert pathologist and radiologist to provide comprehensive and appropriate management of this clinical entity.

Medical history and physical examination of the patient adds significantly to the determination of the nature of the thyroid nodule. Currently, a variety of serologic and cytogenetic tests, diagnostic imaging studies, and histopathologic techniques exist for the evaluation of a thyroid nodule. Of these methods, FNAC has become the most important tool in the assessment of solitary thyroid nodules.

Exposure of the head and neck to radiation increases the incidence of thyroid nodules.

A thyroid nodule can be non cancer (benign) or cancer (malignant).

Benign (Non Cancer) Thyroid Nodules

Thyroid adenomas

Thyroid adenomas are benign tumors which are usually called as follicular adenomas.

Hyperplastic nodules

Hyperplastic nodules can be differentiated from colloid goiters on microscopic examination.

Thyroid cysts

Thyroid cysts represent 15-25% of all thyroid nodules and contains fluid only inside nodules. Sometimes, they can be cancerous also.

Thyroiditis

Swelling of Thyroid (Thyroiditis) sometimes present with nodules also.

Malignant (Cancer) Thyroid Nodules

Thyroid cancer represents approximately 1% of all new cancers and 92% of all endocrine gland cancers. However, the incidence of hidden cancers is quite large and has been reported in the range of 4.2-10% of all post mortems.

The sex and age of the patient appear to play an important role in the outcome of patients with malignant nodules of the thyroid gland. Although solitary thyroid nodules are found more frequently in women, incidence of carcinoma in solitary thyroid nodules is increased in men.

History of prior radiation exposure is an important risk factor for thyroid carcinoma. The risk of developing thyroid carcinoma increases following radiation exposure and is dose-dependent. Other risk factors include preexisting benign thyroid disease, family history of thyroid malignancy, certain inherited syndromes, and residence in endemic goiter areas.

What to do?

Thorough check up of the patient with solitary thyroid nodule includes history of the thyroid mass, past medical history, family and social history, a careful review of all systems, and a complete head and neck examination.

Symptoms such as neck pain, breathing difficulty, voice change, and difficulty in swallowing increase clinical suspicion of a thyroid malignancy; however, none is diagnostic. Prior history of radiation exposure should be ascertained in all patients presenting with solitary thyroid nodule. Past medical history or family history of diseases like pheochromocytoma, hyperparathyroidism, chronic constipation and diarrhea, hypertension, and episodes of nervousness or excitability should alert the clinician of the possibility of familial thyroid cancers like MEN2a or 2b syndrome.

Physical characteristics of a thyroid nodule are important guide to find cancer. Nodules with increased size have higher chances of being cancerous. Also nodules with size >4 cm should be taken with caution only as high chances of being cancer when >4 cm. Fixation to or invasion of surrounding structures and the presence of palpable lymph nodes in the neck are also highly suggestive of malignancy. Vocal cord paralysis is also seen mostly in cancerous nodules.

Thyroid function tests (T3, T4, TSH) should be obtained as part of the initial evaluation of solitary thyroid nodule, and findings are usually normal in patients with thyroid cancer. Metabolic evidence of hyperthyroidism is more commonly associated with benign disorders such as an autonomously functioning adenoma or Hashimoto thyroiditis.

The measurement of serum thyroglobulin levels has not been recommended in the evaluation of solitary thyroid nodule because it is also elevated in benign thyroid disorders. Serum calcitonin and carcinoembryonic antigen (CEA) levels are usually elevated in patients with medullary thyroid cancer (a special type of cancer).

DNA testing has proven to be an effective method for the diagnosis of MEN 2a and 2b syndromes which are associated with Medullary Thyroid Cancers. RET proto-oncogene is the gene tested for this cancer. All family members should undergo similar testing if a RET mutation is identified. Family members with the RET mutation should undergo genetic counseling and should undergo thyroid removal surgery even when there is no nodule or cancer in them.

Diagnostic Imaging

Ultrasonography

Ultrasonography is a safe and effective method of determining the size and the presence of solid or cystic components within a thyroid nodule plus to fing the suspicious charachetristics of nodules. High-resolution ultrasonography can be used to determine the presence of nonpalpable nodules as small as 1 mm within the thyroid tissue. The predictive value of several ultrasonic features of thyroid nodules, including calcifications, margins, and vascularity, have been examined by numerous studies.

The addition of elastosonography in combination with high-resolution ultrasonography has significantly improved the diagnostic accuracy of ultrasound.

Nuclear Scans

Nuclear Scans had been the mainstay in the evaluation of solitary thyroid nodule. Thyroid nodules are classified into cold, warm, and hot according to these scans. Cold nodules have higher chances of becoming cancerous as compared to warm and hot nodules.

If TSH is low, then patient should undergo this scan first and not FNAC.

Other imaging techniques

CT scan and MRI scan have also a role in the initial evaluation of solitary thyroid nodule. The role of positron emission tomography (PET) scan in the preoperative evaluation of follicular or indeterminate nodules is not recommended. Routine use of PET scans in the evaluation of solitary thyroid nodules is not recommended at the present time.

Fine-Needle Aspiration Cytology

Fine-needle aspiration cytology (FNAC) has become the initial diagnostic tool of choice for the evaluation of solitary thyroid nodule. Although needle biopsy can be performed easily, consistently obtaining adequate tissue and processing the specimens to achieve accurate cytopathological interpretation requires expertise and experience. A satisfactory specimen should contain at least 5 or 6 groups of 10-15 well-preserved cells. Aspirated specimen is placed on glass slides and air-dried or fixed for staining. The adequacy of the specimen should be determined under the microscope by the pathologist before the patient leaves FNAC room.

The main limitation of FNAC is the differentiation of benign from malignant follicular neoplasms. FNAC specimens of follicular neoplasms and Hürthle cells are commonly interpreted as indeterminate or suspicious. Diagnosis of follicular cancer also requires the identification of capsular and/or vascular invasion, which is not a possibility with FNAC techniques. Therefore, several techniques in addition to FNAB have been developed to increase the accuracy of FNAB for follicular carcinomas, including immunocytochemistry techniques, large needle biopsy, and intraoperative frozen section analysis.

Intraoperative frozen section analysis of thyroid nodules requires operation and then subjecting the tissue removed to frozen section biopsy. Some authors report a high degree of accuracy with intraoperative frozen section; however, its contribution to the management of solitary thyroid nodules remains controversial.

Management Strategy

Depending on the interpretation of tests done, management consists of observation only with serial monitoring of nodule or medicines or surgery.