Eric S. Albright, MD
Assistant Professor of Medicine
Department of Endocrinology, Diabetes & Metabolism

Samuel W. Beenken, MD
Professor of Surgery Medicine
Department of Surgery- General Surgery Oncology Section

The University of Alabama at Birmingham
Birmingham, Alabama

In accordance with the Accreditation Council for Continuing Medical Education Standards for Commercial Support, Dr. Albright discloses the following: consultant Pfizer, Aventis; honoria Takeda, Pfizer, Aventis, Novartis. Dr. Beenken discloses no conflicts of interest.

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While thyroid nodules are common, thyroid cancer is relatively rare, accounting for less than 2% of cancers in the United States, the American Cancer Society reports. The likelihood of an individual having a nodule equals their age, so a 50-year-old has a 50% chance of having a nodule.

"Up to 7% of all adults will have a palpable nodule during their lifetime, but only 5% of all nodules are malignant, making a thorough initial workup key to avoiding unnecessary surgery in patients with benign nodules," says UAB surgical oncologist Samuel W. Beenken, MD, a member of the panel that authored the National Comprehensive Cancer Network's 2005 clinical practice guidelines for care of patients with thyroid cancer.

Malignant Tumor Types:

There are four main types of thyroid cancer: papillary, follicular, medullary, and anaplastic, explains endocrinologist Eric S. Albright, MD, who works closely with Beenken to provide comprehensive medical and surgical management for patients with thyroid cancer.

More than 90% of malignant thyroid tumors are papillary or follicular carcinomas or their variants, collectively known as well-differentiated thyroid cancer. This article focuses on this group of malignancies.

Papillary cancer accounts for 80% to 85% of well-differentiated thyroid malignancies. Lymph node invasion is common, and in some cases, disease can metastasize to the lungs, bone, and soft tissue, Albright says.

Follicular cancer makes up 5% to 10% of cases, and distant metastases occur more frequently than in papillary cancer. It has a slightly worse prognosis and tends to strike older individuals, he says. "Treatment strategies are similar for different types of well-differentiated thyroid cancer. Most of these malignancies progress slowly, and few individuals die of their disease."

Medullary thyroid cancer is the only thyroid malignancy originating in parafollicular cells rather than follicular cells. Most individuals have sporadic disease, but 20% have an inherited form that often develops in childhood or early adulthood. Genetic testing for the mutation that causes familial medullary thyroid cancer and counseling for at-risk families is available through UAB's Department of Genetics.

The anaplastic form of thyroid cancer is rare (occurring in <2% of cases) and aggressive, killing most patients within a year of diagnosis, Albright says.

Thyroid nodules are frequently found during routine physical examination. "Once a nodule is identified, physicians should refer patients to someone with experience evaluating and treating thyroid conditions. A thorough medical history and physical examination yield important clues for distinguishing benign and malignant thyroid abnormalities," Albright says.

"Patients with a family history of thyroid cancer have a 10-fold risk of developing cancer. A history of low-dose radiation exposure from radioactive fallout or childhood head or neck irradiation also increases risk," he says.

Age and gender are important diagnostic indicators, as well, Beenken says. "Although women have higher rates of thyroid cancer, thyroid nodules in men are more likely to be malignant, as are those in people younger than 15 or older than 65."

A high index of suspicion for cancer is warranted in patients with enlarging thyroid nodules, difficulty swallowing, or hoarseness, and these individuals will eventually have surgery, Beenken says. Most patients are asymptomatic, however, and should be evaluated with ultrasound, which cannot exclude cancer but can reveal nodular characteristics that further stratify risk. Thyroid function tests rule out other disorders, and fine needle aspiration (FNA) biopsy of nodules >1 cm is indicated for definitive diagnosis.

"FNA is key to thyroid nodule assessment, and cytology reveals 1 of 4 results: benign, malignant, suspicious, or insufficient biopsy tissue," Albright says.

Benign nodules are re-evaluated after 6 months with clinical follow up and imaging and then every 2 to 5 years with repeat FNA, depending on a patient's risk factors. Repeat FNA is performed earlier if the nodule's size increases more than 15% in a year. Rapid growth within a few months is an indication for surgery, he says.

In asymptomatic patients, nuclear medicine scans are generally of no clinical utility, Beenken says. "In most cases, nuclear scans offer no information not provided by a history, physical exam, ultrasound, thyroid function studies, and FNA. If cancer is confirmed or a risk of malignancy is indicated, patients are scheduled for surgery."

Lobectomy VS Total Thyroidectomy:

Patients with well-differentiated thyroid cancer are stratified into low, intermediate, or high-risk groups to determine the optimal extent of surgery, Beenken says."Low-risk patients require only lobectomy with identification and preservation of the ipsilateral recurrent laryngeal nerve. Less than 5% develop recurrent cancer in the unresected lobe, which can almost always be resected."

Low-risk patients are young adults (women aged <45 years, men aged <40 years) with a solitary tumor 2 cm, no extracapsular extension, and no lymph-adenopathy. "Complications of total thyroidectomy — hoarseness, hemorrhage, and hypoparathyroidism — occur in 1 of 100 patients, but the rate is higher than with lobectomy," Beenken says. Lobectomy minimizes these risks in low-risk patients.

High-risk patients (those with known distant metastatic disease) should be treated with total thyroidectomy with identification and preservation of both laryngeal nerves and at least one viable parathyroid gland, Beenken says. Individuals at extremes of age may also harbor more aggressive tumors.

These recommendations are nationally accepted, but treatment of intermediate-risk patients (60% of all thyroid cancer cases) is more controversial, says Beenken, who usually performs a total thyroidectomy in these patients. Thyroidectomy simplifies postsurgical use of 131I and allows biochemical follow up instead of heavy reliance on imaging.

A retrospective analysis by Beenken and colleagues of patients at UAB and M.D. Anderson Cancer Center in Houston, Texas, reviews optimal treatment strategies for intermediate-risk patients (Am J Surg. 2000;179:51-56).

Radioactive Iodine Therapy:

"In patients with well-differentiated thyroid cancer, postsurgical 131I ablation destroys residual thyroid tissue and helps eradicate any metastatic disease," Albright says. "Once all residual tissue is gone, patients are monitored for cancer persistence or recurrence with a blood test for thyroglobulin, which should be undetectable after thyroidectomy and remnant 131I ablation. In 90% of cases, a measurable rise in thyroglobulin signals recurrence, and any level above the detectable range indicates persistence."

Patients treated with lobectomy have residual thyroid tissue that prevents the use of thyroglobulin and 131I scans for monitoring. In these patients, monitoring is accomplished with physical examination, ultrasound, or computed tomography of the neck.

After surgery, patients must take lifelong thyroid hormone replacement therapy to prevent hypothyroidism and suppress thyroid-stimulating hormone (TSH) serum levels.

"TSH is a growth stimulating factor for thyroid tissue," Albright says. "Therefore, suppressive thyroid hormone therapy is essential." Thyroid hormone therapy may be periodically withdrawn to enhance accuracy of radioactive iodine scanning and thyroglobulin measurement.

"When a 131I scan is indicated, TSH levels are increased by withholding thyroid hormone for 4 weeks or by administering 2 doses of thyrotropin alfa — recombinant TSH made from hamster ovaries," Albright says. "Thyrotropin alfa allows patients to continue their thyroid hormone, which helps prevent hypothyroid symptoms and limits TSH stimulation of any residual tumor."

Elevated TSH levels provide for better uptake of 131I. Desired postsurgical TSH serum levels are stratified based on graded severity of the cancer and are set below the normal range, Albright says. "These targeted levels are different from those for primary hypothyroidism where TSH levels are set within the middle of the normal range. For cancer patients, thyroid hormone is regulated to precise levels, and adjustments should always be made in consultation with a patient's endocrinologist."

Patients with elevated thyroglobulin are treated with ablative 131I therapy every 6 to 12 months, until thyroglobulin levels are undetectable.

"After two negative scans and one undetectable stimulated thyroglobulin level, treatment ends and monitoring begins. Recurrence, usually localized to the neck, is most likely during the first 5 years following surgery," Albright says.

Patients are evaluated with a physical exam every 3 to 6 months and a serum thyroglobulin level once a year for the first 3 years. "Although national guidelines recommend an annual chest X-ray for the first 5 years, I prefer serum thyroglobulins and 131I scans as primary screening modalities," he says.

UAB's experienced specialists provide multidisciplinary care for thyroid cancer patients. In addition to Beenken and Albright, patients are treated by Department of Sur-gery Chair Kirby I. Bland, MD, Director of the Division of Otolaryngology-Head and Neck Surgery Glenn E. Peters, MD, and endocrinologist Richard S. Rosenthal, MD.

For more information:

Dr. Eric Albright
Dr. Samuel Beenken
1-800-UAB-MIST
mist@uabmc.edu

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