The following is the first article in a two-part series on thyroid cancer, the incidence of which has increased dramatically over the past two decades. This first article focuses on what's behind this increased incidence; the second will address its impact on the treatment of thyroid cancer.

Since the early 1970s, the incidence of thyroid cancer has more than doubled. Among women, in fact, it is the cancer with the fastest rising number of new cases.

Nevertheless, it's still a relatively uncommon cancer, with approximately 33,500 new cases annually, and 1,500 deaths, most of which are due to rare, aggressive types.

But not quite 2 years ago, Dartmouth College researchers, relying on data from NCI's Surveillance, Epidemiology, and End Results (SEER) program, concluded that the increased incidence of thyroid cancer was an illusion. The study's authors, Drs. Louise Davies and H. Gilbert Welch, laid the blame for the increase on "greater diagnostic scrutiny" - a byproduct of sensitive imaging technologies and advanced biopsy techniques. It's most likely a case, they argued, of "overdiagnosis."

According to some of the country's leading endocrinologists and endocrine surgeons, who are responsible for diagnosing and treating most thyroid cancers, the study made a convincing case. First, the vast majority of the increase, 87 percent, was attributable to cancers smaller than 2 centimeters, nearly all of which are the most treatable and common type, papillary thyroid cancer. Autopsy studies, in fact, have consistently shown that, at death, a significant portion of people can have small, malignant papillary thyroid nodules, ranging from several percent to 36 percent in one study.

In addition, despite the increased incidence, there was no associated change in mortality rates, which have remained very low. Treatment of truly life-threatening cancers would have to improve to keep mortality stable, they argued, and while treatment trends have changed, there is little evidence to suggest they have influenced mortality one way or the other (the subject of the second article in this series).

Both factors suggest greater detection of "subclinical" disease, Drs. Davies and Welch argued, not some unknown influence spurring the development of more thyroid cancers.

That conclusion, however, leaves one big question: In the absence of any directed efforts toward early detection - such as those for breast or colon cancer, for example - why is anyone looking for these unobtrusive nodules in the first place?

Very often, explains Dr. Keith Heller, an endocrine surgeon at New York University Medical Center, these tiny cancers are discovered "by accident" during imaging procedures being done for other reasons, such as carotid duplex scans looking for peripheral vascular disease in neck arteries or MRI and CAT scans following car accidents or for unexplained neck pain or severe headaches.

It then falls to endocrinologists, many of whom now have ultrasound machines in their offices, to take a closer look at the thyroid.

"That's how I get the majority of my referrals," says Dr. Jennifer Sipos, an endocrinologist at the University of Florida, "nodules that are incidentally found…on an [imaging procedure] taken for another reason."

There also is some unnecessary testing going on, Dr. Heller believes.

"I had a patient the other day who came in because her GP ordered a thyroid ultrasound because she was gaining weight," he recounts.

And thanks to a technique known as ultrasound-guided fine-needle aspiration, these tiny nodules are relatively easy to biopsy.

"When I was a fellow in the early 90s, we couldn't easily biopsy a nodule that was 1 centimeter or less," says Dr. R. Michael Tuttle, an endocrinologist at Memorial Sloan-Kettering Cancer Center. "But, over the last 10 years, techniques have advanced such that we can now easily biopsy nodules that are less than 4 or 5 millimeters."

However, Dr. Tuttle says he's not convinced that the increased incidence of thyroid cancer is solely an artifact of better technology.

"My concern is that if we blame this entirely on early detection, we may be missing some other cause of thyroid cancer," he says. "I don't think any of the data we have rule out some other etiology."

There are some data to support that concern. A more recent, unpublished analysis of SEER data (through 2004) by Dr. Susan Devesa, from NCI's Division of Cancer Epidemiology and Genetics (DCEG), indicates that the increased incidence, while most prominent for smaller tumors, has occurred across all tumor sizes (even 5 centimeters and larger) and stages, suggesting that more intense scrutiny isn't solely responsible for this trend.

Some studies have suggested that factors such as body mass index, diet, and reproductive patterns can influence thyroid cancer risk. One factor now coming under increasing scrutiny, ironically, is diagnostic imaging, namely CT scans.

The number of CT scans performed annually has exploded, from just a few million in the early 1980s to an estimated 62 million in 2006. CT scans require higher radiation doses than other conventional imaging techniques - doses that, according to a recent paper by Drs. David J. Brenner and Eric Hall from Columbia University Medical Center, are in a range that could increase cancer risk.

"Given the relatively short latency period for radiation-induced thyroid cancer…it is quite possible that CT is influencing current thyroid cancer rates in the United States in young people," says Dr. Brenner, of the Center for Radiological Research at Columbia.

Dr. Elaine Ron, an expert on ionizing radiation and thyroid cancer in NCI's DCEG, agrees that CT scans do represent a potential risk. But, she stresses, "We don't have any data that show that at this point."

To better assess the risk of all cancers and CT scans, Dr. Ron says, NCI is collaborating with researchers from the United Kingdom on a retrospective "historical cohort study" of close to 200,000 people in the U.K. The study will look at cancer rates in people who did and didn't receive CT scans as children.

—Carmen Phillips