April 2009
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Diagnosis and Management of Thyroid Nodules: An Overview
Thyroid nodules are very common and frequently benign.
Reviewed by Hossein Gharib, MD; By Conni Bergmann Koury, Editor-in-Chief
There have been many recent advances in the diagnosis and management of thyroid nodules. These betterments include the introduction of new thyroid-stimulating hormone (TSH) assays, widespread application of fine-needle aspiration (FNA) biopsy, and the availability of high-resolution ultrasonography (US). These new techniques have improved patient care, but some aspects of thyroid nodule management remain controversial, according to Hossein Gharib, MD, MACP, MACE, writing in Endocrinology and Metabolism Clinics of North America.1
The American Association of Clinical Endocrinologists, the Associazione Medici Endocrinologi,2 and the American Thyroid Association3 are the main sources of evidence-based recommendations. Dr. Gharib is Professor of Medicine, Mayo Clinic College of Medicine, President, American College of Endocrinology, and Past President, American Association of Clinical Endocrinologists.
BACKGROUND
In an interview with Review of Endocrinology, Dr. Gharib said that it is important for physicians to recognize that thyroid nodules are very common and that they are usually benign. "They are discovered when the physician does a careful neck examination or when a patient looks at his or her own neck and finds a lump, or they can be found incidentally," he said. Prevalence increases linearly with age, exposure to ionizing radiation, and with iodine deficiency, and nodules are more common among women than among men. Framingham calculates the incidence as 100 cases per 100,000 persons per year.4
Infrequently, thyroid nodules can cause compressive symptoms, however, the most important feature of nodules is that they may indicate thyroid cancer. Regardless of the size, about 5% of all thyroid nodules are cancerous.5 Dr. Gharib said that the general endocrinologist is the clinician most appropriate and experienced to evaluate and manage patients with thyroid nodules. Often other clinicians will detect and diagnose thyroid nodules, but to give patients the best care, they should be referred to an experienced clinical endocrinologist.
DIAGNOSIS AND DETERMINATION
Once a thyroid nodule is discovered, the next step is to make a determination of the patient's risk factors for cancer. Although general risk factors are low across the board for thyroid cancer, and most often nodules are likely to be benign, in some populations nodules are more important and more risky, Dr. Gharib said.
The presentation of nodules during childhood and adolescence should be evaluated with caution, whereas a nodule in an 80-year-old woman is probably benign. Head and neck radiation exposure increases risk for malignancy, as does a strong family history. Findings on palpation, ultrasound, and biopsy, will indicate if the nodule is benign or malignant.
US. When a patient is suspected or confirmed to have a nodule, thyroid US is recommended by all guidelines as the first step for further evaluation. According to guidelines, brightness-mode US is the most sensitive test to detect lesions in the thyroid. US is noninvasive, relatively inexpensive, and can identify nodules not apparent on physical examination, isotope scanning, or other imaging techniques.6 It is important to note, however, that because of the high prevalence of small, clinically inapparent thyroid nodules and the minimal aggressiveness of most thyroid cancers, US should be used as a screening test only if well-known risk factors are present.
TSH. The next step is to measure serum TSH, a determination of thyroid function. "If TSH is low or suppressed, biopsy may not be necessary and we proceed to a thyroid radioisotope scan," Dr. Gharib said. TSH is the most useful test in the initial evaluation of thyroid nodules because of the high sensitivity of the TSH assay in detecting early or subtle thyroid dysfunction.7,8
FNA. In most cases the nodules are solid and TSH is normal, and therefore a FNA biopsy would be the next step. Dr. Gharib said that FNA can be done either by direct palpation or preferably, through the use of US-guided FNA. "Most endocrinologists use US to detect and measure the thyroid nodule and therefore they are likely to use US-guided biopsy," he added. The use of US-guided FNA has become increasingly popular because of its precision and the ability to guide the biopsy needle to the desired location in real time.6
MANAGEMENT
Clinical management of thyroid nodules is based on the information gathered from the combined results of TSH measurement, FNA biopsy, and US. "If cytology on FNA is either suspicious (indeterminate) or malignant, then surgical consult and thyroidectomy follow," said Dr. Gharib.
If the nodule is small and primarily cystic by ultrasound, a biopsy may not be needed and the patient can be simply followed. If the nodule is solid and benign by FNA, Dr. Gharib said the patient is then followed and a repeat US is performed in 1 year. That nodule can be examined without necessarily doing a repeat biopsy.
Suppressive therapy. The use of T4 suppressive therapy in nodular thyroid disease is not recommended,2,3 and most thyroid nodules do not need specific treatment if malignancy and abnormal thyroid function have been excluded, according to guidelines. Unless the nodule (or nodules) is causing local symptoms or if the patient has excessive concerns regarding the prominence of the nodule, treatment aimed at volume debulking or growth prevention is unnecessary. Clinical and US follow-up should however, be performed every 1 to 2 years.
Surgery. If a single, benign nodule is considered for surgical removal, a partial thyroidectomy or lobectomy is preferred. "If there is a nodule in the right lobe of the thyroid that is large, and there are several smaller ones in the left lobe, that patient is best treated with a near-total thyroidectomy," Dr. Gharib said. The rationale for this is that small nodules may grow into bigger problematic ones and reoperation is always more difficult, he added. Of course if the nodule turns out to be malignant at surgery, then a near-total thyroidectomy is the procedure of choice.
Complications. There can be complications following thyroidectomy, such as hypothyroidism requiring thyroxine therapy. Vocal cords can be damaged and hoarseness is an additional complication. Damage to parathyroids can cause hypoparathyroidism; however, thyroidectomy is a low-risk surgery in the hands of experienced clinics and surgeons.
MORE ON TSH
A normal TSH measurement is from 0.3 to 3.0 ľU/mL. If a nodule exists in the setting of low or suppressed TSH, it should be thought of as hyperfunctioning and a radioisotope scan should be performed, Dr. Gharib said. Guidelines state that thyroid scanning is the only technique that allows for assessment of thyroid nodular function and detects areas of autonomy within the thyroid gland. "If the patient has a TSH measurement of 6 to 8 ľU/mL, then we measure thyroid antibodies because we think of automimmune disease or Hashimoto's as the underlying mechanism for nodule formation. Additionally, there is some recent evidence that TSH levels allow some degree of risk factor analysis for cancer," Dr. Gharib said.9,10
If serum TSH is low, 0.2 or 0.5 ľU/mL, the chance for a nodule being malignant is low, and if TSH is increased, the risk for cancer increases, according to Dr. Gharib. According to a recent report, if a woman has a nodule and TSH is 0.3 ľU/mL, the calculated risk for cancer was 8%. In the same patients, a 40-year-old female with a single nodule and a TSH of 6.0 ľU/mL carries a 26% increased risk for cancer. "This is emerging data that some endocrinologists and most other physicians are not aware of," Dr. Gharib said.9
CALCITONIN
There is some controversy surrounding the use of calcitonin measurements in the setting of nodular thyroid disease. Calcitonin is a hormone that comes from special thyroid gland cells, but it is not a part of the thyroid itself. Dr. Gharib noted that medullary thyroid cancer is associated with increased level of calcitonin, therefore some experts have suggested measuring calcitonin routinely. This process of measuring calcitonin involves the use of a stimulator called pentagastrin. This agent, however is no longer available in the United States or some European countries.
"We have not accepted routine use of calcitonin in the United States," Dr. Gharib said. "There are some practitioners in Europe who do measure it, and this area remains controversial." Medullary cancer accounts for less than 5% of thyroid cancers. There is a total of 35,000 new cases a year in the United States, Dr. Gharib said.
CONCLUSION
Thyroid nodules are common and carry a 5% risk of malignancy. It is a challenge of management to identify benign nodules and accurately diagnose and treat malignancies early. Dr. Gharib wrote in Endocrinology and Metabolism Clinics of North America that the current treatment plan using TSH measurement, US, and FNA as initial tests, followed by US-guided FNA when necessary, seems to be practical, efficient, and cost-effective.
Hossein Gharib, MD, MACP, MACE, is Professor of Medicine, Mayo Clinic College of Medicine; President, American College of Endocrinology; and Past President, American Association of Clinical Endocrinologists. He may be reached at gharib.hossein@mayo.edu; phone: 507-284-9576; or fax: 507-284-5745.
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