With Thyroid Nodules, Bigger Doesn’t Always Mean Bad

With Nicole Cipriani, MD, and Luba Naqi, MD

Thyroid nodules—lumps on the thyroid gland that may or may not be noticeable to you—are very common. About half of women reaching the age of 50 years have at least one nodule, and by 70 years, nearly 70% do.1 And while they are most common in women, about one in 40 young men are affected.1

While more than 95% of all such thyroid nodules are benign, meaning non-cancerous, doctors have been trying to determine for years how best to predict which of the few might become malignant out of the vast majority that will remain harmless.

New evidence,2 published in the journal Thyroid, suggests that even larger nodules are no more likely than smaller ones to develop into thyroid cancer.

"Size alone is not a risk factor for malignancy," says lead author Nicole Cipriani, MD, assistant professor of pathology, University of Chicago Medical School in Illinois. She considers the findings reassuring for patients, particularly because most thyroid nodules are detected by accident, which then raises concerns and causes  patients to worry unnecessarily.3

A Crash Course in Thyroid Nodule Evaluation to Ease Your Mind

The two most common methods that your doctor uses to evaluate thyroid nodules are ultrasound imaging and fine needle aspiration biopsy. When a biopsy is done, a sample of tissue from the nodule is obtained and sent to the lab for analysis.

For more detail: Patient Thyroid Cancer Guide

The thyroid cells are then classified according to the Bethesda System,4 which assesses thyroid findings based on six categories—from nondiagnostic or unsatisfactory to benign, abnormal but of undetermined significance, suspicious for neoplasm (abnormal growth), suspicious for malignancy, and malignant. The categories reflect estimated cancer risk from 0% in the first category to 100% for confirmed cancer for the sixth group.

Categories III and IV, reflecting nodules that are abnormal but of unknown concern and those that are suspicious for abnormal growth, ''are the ones that drive the patient and the doctor nuts,'' as has been unclear about what to do, Dr. Cipriani says, since we don’t want to treat too aggressively without sufficient benefit.

To date, studies have shown mixed results, she says, with some evidence suggesting that larger nodules may be more likely to become cancerous while other data finding that size is not linked with malignancies. So Dr. Cipriani and her team set out to find a more certain answer to give patients and their doctors a clearer idea of when and if it is necessary to treat bigger thyroid nodules more aggressively than small nodules.2

Searching for an Answer About Larger Thyroid Nodules

The Chicago Medical School researchers conducted what is known as a meta-analysis, which involves looking at already published studies and considering the findings based on cumulative data to determine whether there are solid trends. For this systematic review of the literature,2 Dr. Cipriani and her team looked for studies published on or before December 8, 2017. They identified 352 citations and then pared them down to 35 articles that fit their focus most closely.

The studies they reviewed involved thyroid nodules that were classified by size—from 3 to 5 centimeters (cm); a thyroid nodule less than 1 centimeter is considered small. The team also looked at which nodules were classified as cancerous; all of the nodules in these studies were removed surgically.2

What they found is that the rate of malignancy was not substantially different relative to the size of the thyroid nodule. In fact, the cancer rate for nodules that were 3 cm and greater was 13.1% as compared to the rate of malignancy for thyroid nodules less than 3 cm was 19.6%. And for thyroid nodules over 4 cm, the cancer rate was 20.9%, nearly the same as that for thyroid nodules (19.9%) for similar nodules less than 4 cm.2

Next, the researchers looked at the reports of false-negative occurrences—defined as a nodule that is defined as benign when the cells are examined at biopsy but turns out to be malignant based on the final pathology report following surgery to remove the nodule.2 Here too, the size of the nodule did not appear to play a role in whether reports of false-negative results.

"Size alone is not a risk factor for malignancy," Dr. Cipriani tells EndocrineWeb. "You do not have an increased risk of cancer with increasing size.''

"If your biopsy is benign, the risk of it being cancer if it is resected [removed surgically] is not different for large versus small nodules," she says.1

The findings should reassurance patients, she says. "A lot of people are scared by size."

You’ve Been Diagnosed with a Large Thyroid Nodule—Should You Be Concerned?

The findings from this meta-analysis should prompt you to have a frank discussion with your physician, Dr. Cipriani tells EndocrineWeb.

“Many other factors come into play in deciding whether to choose to have surgery to remove a nodule,” she says. Certainly If after hearing all the pros and cons of having surgery, and still feeling too unsettled with the idea of active surveillance (watchful waiting), then this discomfort must be addressed in the discussion about treatment options and options for next steps, for instance.

On the other hand, for patients who are older and at greater risk of complications from surgery for a thyroid nodule that poses no issues and isn’t bothering them, that too should be considered, she says.

What was not known from the studies that Dr. Cipriani's team evaluated is the interval between the biopsy and the surgery? When surgery is done, she says, the usual procedure is to remove at least one of the two thyroid lobes. To surgically remove just a nodule is more complicated, she says, but this means that the patient may not need thyroid replacement hormone, which, if necessary, must be taken for the remainder of the patient’s life.

When patients choose to have their thyroid nodule monitored, a management process called active surveillance,5,6 the patient returns every 6 to 12 months for a biopsy to check for any cellular changes—and this is the current strong recommendation from all of the professional organizations—and then if the thyroid nodule is found to be cancerous, Dr. Cipriani says, it is very treatable.5

Less Need for Surgury Is Good News for Patients Long-Term

This nice meta-analysis of thyroid nodules looks at size and risk of malignancy, says Lubna Naqi, MD is a double board certified physician in Internal Medicine and Endocrinology with Pacific Coast Family Medical Group in Redondo Beach, California, who reviewed the study for EndocrineWeb.

“I do not recommend thyroidectomy based on thyroid nodules size only,” she says. “Patients have to be symptomatic or the biopsy should show evidence of thyroid cancer in order for me to recommend surgery.

Nowadays, I can order molecular studies to rule out cancer—essentially to see if the results are indicative of a follicular lesion of undetermined significance or suspicious for follicular neoplasm.” In this way, clinicians can avoid unnecessary surgeries.

“Needless thyroidectomies can sometimes result in recurrent laryngeal nerve paralysis and a hoarse voice, as well as increase the possibility of low calcium and a need for lifelong thyroid supplementation depending on total vs. partial thyroidectomy.

So, I’m not surprised by the research findings from this meta-analysis, which should definitely be reassuring for patients,” Dr. Naqi told EndocrineWeb.  For most forms of thyroid cancer, the five-year survival rate is nearly 100% when it is detected early,7 according to the American Cancer Society.

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