By Antonio C. Bianco, MD, PhD
Within two weeks of each other, two patients arrived in my office with almost identical stories. Both were middle-aged teachers who had lost their jobs months after being diagnosed with hypothyroidism, or an underactive thyroid. They had gained weight, lost energy and had trouble focusing.
Yet their hypothyroidism was under control, as judged by medical standards. They were taking the go-to medication that has been prescribed for hypothyroidism for 40 years, a synthetic thyroid hormone called levothyroxine. Blood tests revealed that the women had normal thyroid-stimulating hormone (TSH) levels, which is the lab value physicians look at to diagnose and manage hypothyroidism. Frustrated over their lingering symptoms, both women had sought second opinions from numerous endocrinologists. All of these specialists assured the women that their lab tests were normal and they should feel fine.
About 15 percent of people with hypothyroidism, including 2 million Americans, remain symptomatic despite following what we physicians call the standard of care, which has been recommended by the American Thyroid Association. Just like my two patients, these patients are fatigued, sluggish. Their cognition is compromised and they gain weight that they can’t lose. They are commonly depressed, and their lives are significantly impaired.
Search for evidence
Physicians often dismiss these complaints from hypothyroid patients as “all in their heads.” I should know. I used to be one of those physicians. Then eight years ago, because of these two patients and their strikingly similar stories, I started to listen more closely to what my patients were saying. As a result, I started to believe them.
But I needed proof that my patients were exhibiting real and not fictional symptoms. Toward this end, my colleagues and I looked at individuals enrolled in the U.S. National Health and Nutrition Examination Survey (NHAMES). As described in a study in the Journal of Clinical Endocrinology and Metabolism, we focused on about 10,000 participants with normal TSH levels. About 470 of these individuals were treated with levothyroxine. Compared to healthy matched controls, the individuals on the levothyroxine exhibited many of the problems reported by my two patients. They were about 10 pounds heavier, despite consuming fewer calories, and were significantly less physically active. The individuals were also more likely to be on antidepressants, as well as statins (typically prescribed for high cholesterol) and beta blockers (commonly taken for high blood pressure).
To our knowledge, this study presents the first objective evidence that the lingering symptoms reported by so many people with hypothyroidism are real, and not in their heads. The next step is to find a way to successfully treat all patients, which will require physicians, scientists and the pharmaceutical industry to revisit what we know about hypothyroidism.
The thyroid gland, which is in the neck, works very closely with the pituitary gland at the base of the brain. Together, they ensure the body has adequate supplies of two thyroid hormones: triiodothyronine (T3) and thyroxine (T4). These hormones are critical in regulating the body’s metabolism, from the number of times the heart pumps to the ability of the brain to process thoughts. When these hormones are low, as in hypothyroidism, everything slows down from digestion to cognition.
The thyroid mostly produces T4, which is considered an inactive hormone because it primarily exists only to be converted into T3, the active hormone. As T4 travels through the body, an enzyme called deiodinase transform T4 into T3.
The pituitary gland’s role is to keep an eye on the levels of T4 in circulation. When T4 is low, the pituitary gland secretes TSH into the blood stream, rousing the thyroid to produce more T4.
Most people develop hypothyroidism due to an autoimmune disorder. For reasons not entirely clear, the immune system no longer recognizes the thyroid as a natural part of the body and begins producing antibodies and killer cells to destroy the gland.
Rather than fix the failing thyroid, physicians prescribe the medication levothyroxine, or the synthetic version of T4. Scientifically, we assume deiodinase enzymes will convert the T4 in levothyroxine tablets into T3, providing the body with sufficient thyroid hormones. We then adjust the dose of levothyroxine until TSH levels are in the normal range.
‘How big a deal?’
Why would people with normal TSH levels not feel well? Many theorize that this is due to low blood levels of T3. In other words, the body is not capable of converting the T4 contained in the levothyroxine tablets into sufficient amounts of T3. The study of the NHAMES population confirms this. Patients on levothyroxine exhibited 5 percent to 10 percent lower circulating levels of T3.
How big a deal is it to have a slightly lower blood T3? The reality is that we do not have good way of answering this question because currently available synthetic T3 is short lived, with levels fluctuating rapidly in the circulation. Safety might be an issue as well. Peaks of T3 in the blood cause heart palpitations in many patients. Common sense suggests this might not be safe, particularly in elderly patients or those at risk for heart disease.
We need help from the pharmaceutical industry in identifying new formulations of T3. In the meantime, physicians now have objective evidence that having normal TSH levels does not preclude a substantial number of hypothyroid patients on levothyroxine from having real debilitating symptoms.
Antonio C. Bianco, MD, PhD, is immediate past-president of the American Thyroid Association, and the Charles Weaver Professor of Medicine at Rush University Medical Center.