What would you guess is the most commonly prescribed medicine in Oregon? A cholesterol or blood pressure drug? Maybe an opioid pain medication or a diabetes drug?
Guess again. It’s a thyroid hormone.
A recent tally by the website GoodRx found that prescriptions for levothyroxine, a synthetic thyroid hormone, were filled by pharmacies in Oregon and 25 other U.S. states more often than any other drug. Some 120 million prescriptions are written for levothyroxine in the U.S. each year, and 15 percent of Americans over age 55 are taking the medication.
“When you look at the overall national list, it regularly tops the list,” said Thomas Goetz, chief of research for the website, which helps consumers find the lowest price on drugs in their areas. “There are 15 million Americans suffering from thyroid disorders. That’s a significant part of the population.”
But many experts believe those numbers are too high, that thyroid problems are being vastly overdiagnosed and overtreated. If true, that would mean many patients are being exposed to potentially serious side effects for no benefit.
Levothyroxine, sold as a generic or under the brand name Synthroid, is used to treat underactive thyroid, also known as hypothyroidism.
Doctors diagnose it by measuring levels of thyroid stimulating hormone or TSH. When thyroid hormone levels are low, the pituitary gland pumps out more thyroid stimulating hormone to spur production, making it a good marker for thyroid problems. Generally, a TSH level under five is considered normal and anything over 10 is a clear-cut case for treatment.
“But when it’s in the five-to-10 range, that’s the gray area,” said Dr. Mary Carroll, an endocrinologist with Summit Medical Group Oregon-Bend Memorial Clinic. “That’s the area in which a lot of people are being prescribed levothyroxine inappropriately.”
Screening for underactive thyroid has become routine among primary care physicians, particular when older patients complain of fatigue, weight gain or difficulty concentrating. An elevated TSH test provides an easy answer and a ready solution. But TSH levels tend to rise naturally with age or weight gain, and that may be leading doctors to overlook other causes.
In one study of more than 420,000 people, about 3 percent had TSH levels between 5.5 and 10. In the next five years, however, three out of five of them returned to normal without any treatment.
Carroll said borderline abnormal tests should be repeated before a patient is put on a medication. For those in the gray zone, an antibody test could identify whether the person has Hashimoto’s disease, an autoimmune condition which is the most common cause of hypothyroidism.
The U.S. Preventive Services Task Force conducted reviews of the evidence around thyroid screening and treatment of patients in the gray zone in 2004 and 2015. Both times, the group concluded there was insufficient evidence to recommend for or against screening, nor to conclude whether treatment makes any difference in patients with mildly underactive thyroids.
Nonetheless, doctors continue to screen for it and may be dropping their threshold for treatment. A 2014 study that reviewed medical records of more than 52,000 patients who were prescribed levothyroxine found the mean level of TSH that prompted doctors to write the prescription declined fairly steadily from 8.7 in 2001 to 7.9 in 2009. That led to a 28 percent increase in the odds a patient with a level under 10 would get a prescription.
With more patients being tested and the threshold of prescribing falling, the rate of patients diagnosed with hypothyroidism, even after adjusting for an aging population, nearly doubled over the eight years of the study.
“Our results suggest that there is widespread prescribing of levothyroxine for borderline (TSH) levels among individuals with limited evidence of benefits,” the authors wrote in medical journal JAMA Internal Medicine.
Dr. Elizabeth Pearce, president-elect of the American Thyroid Association and an endocrinologist at Boston University, said rising rates could represent a real increase in hypothyroidism as the nation gets older and heavier. A documented drop in dietary iodine intake could also be contributing to rising rates. And for people with actual hypothyroidism, there is an urgency to treat. Studies have found a link between low thyroid levels and the risk of heart disease.
But the best prevalence data, she said, dates back to the early 1990s, when about 4.6 percent of Americans over the age of 12 were found to have underactive thyroids.
“If those numbers are still accurate,” Pearce said, “it would suggest there is some overdiagnosis and overtreatment going on at this point.”
That’s especially true among seniors. A TSH of up to 7.5 in 80 year olds, she said, is probably normal. And the older the patients, the less cardiovascular benefit treatment offers. That could tip the balance from benefit to harm.
In fact, studies suggest that many patients in the gray zone don’t seem to benefit from levothyroxine. A randomized controlled trial published in 2017 found no difference in fatigue or other thyroid-related symptoms among patients treated with levothyroxine compared with placebo. Levothyroxine worked exactly as intended, lowering TSH to normal levels, but patients’ didn’t feel any better.
“From my experience, when people do have thyroid problems, it never seems the Synthroid has helped us with fatigue or losing weight,” said Brandi Croom, a 36-year-old real estate agent from Redmond who has taken the hormone since 2009. “It’s definitely not a magic pill — at least it wasn’t for me.”
Croom was diagnosed with hypothyroidism in Alaska in 2009 while she was pregnant. During pregnancy, the body ramps up production of thyroid hormone to supply the amount needed for normal fetal development. Low levels during pregnancy have been linked to miscarriage, preterm birth, low birth weight and low IQ.
She was put on levothyroxine for the duration of her pregnancy and has continued to take it ever since. In 2014, she was diagnosed with thyroid cancer and had her thyroid removed. She now relies on the medication completely for her thyroid hormones.
“I think a lot of people probably do get placed on this drug quickly, but I think a lot of us are tired and have poor diets, and a lot of stress,” Croom said. “And I think it triggers whatever may be underlying before we get on top of it.”
There are also studies suggesting that thyroid cancer may be overdiagnosed and overtreated. Doctors look for nodules on the thyroid that can sometimes progress to cancer. Many patients wind up having their thyroids removed and must take levothyroxine for the rest of their lives. Yet, despite a large increase in the number of thyroid cancer cases diagnosed, the death rate from thyroid cancer hasn’t changed much. The American Thyroid Association said the recent increase in thyroid cancer cases is due, in large part, to identification of tiny cancers that will never result in symptoms or death, and which only rarely grow larger or spread beyond the thyroid gland. Medical imaging is finding nodules so small they aren’t meaningful, and when these nodules are biopsied, only about 5 percent find cancer cells.
“The pendulum has swung really far back toward less extensive intervention for thyroid nodules and thyroid cancer than even 10 years ago,” Carroll said. “It’s usually not a very aggressive disease.”
— Reporter: 541-633-2162, email@example.com