By Shannon Kelleher
BU News Service

When Amanda Zook gained forty pounds in three months the summer after graduating college, she knew that something wasn’t right. Bewildered, she went to see her doctor, who told the twenty-two year old “well, you’re getting older now,” gave her some medication for depression, and sent her on her way. Amanda didn’t trust the “diagnosis”, so a year later she went to see another doctor, who gave her a standard blood test and diagnosed her with hypothyroidism (underactive thyroid). It’s been twenty years since she started taking medication for the disorder, yet Amanda still suffers symptoms: aches and pains, insomnia, hair loss and lack of sex drive. She naps daily and forgets words. “I think it’s actually getting worse,” she says.

Hypothyroidism is riddled with controversy from diagnosis through treatment, and ultimately it’s the patients who bear the brunt of the confusion. There are as many as 27 million people in the United States diagnosed with hypothyroidism, most of them middle-aged women. While standard treatments are effective for some, others, like Amanda, are not getting the balance of hormones they need to feel normal. While some doctors remain relatively satisfied with the state of thyroidology, others contend that the field is in need of change.

The thyroid is a butterfly-shaped gland in the neck that produces the hormones that regulate metabolism. Two of those hormones, T3 and T4, are the most critical and best understood. “Thyroid hormone is kind of like the accelerator pedal or the thermostat,” says Dr. Henry Lindner, a specialist in endocrinology, diabetes and metabolism at the Hormone Restoration clinic in Tunkhannock, Pennsylvania. When thyroid hormone levels are healthy, the body’s metabolism runs smoothly. But if those levels are out of whack, the metabolism is too.

In mainstream endocrinology, the solution to this metabolic imbalance is wrapped up in two controversial elements: a TSH blood test for diagnosis and a synthetic T4-only medication for treatment (commonly a drug called levothyroxine). Thyroid-stimulating hormone, or TSH, is produced by the pituitary gland and stimulates the thyroid gland to produce T3 and T4. Unless the endocrinologist suspects that the patient has a problem with the pituitary gland (which accounts for about 5% of all hypothyroid patients), the doctor tests the concentration of TSH in the patient’s blood as a measure of how well her thyroid is functioning. The pituitary gland produces excess amounts of TSH in an effort to jump-start the sluggish thyroid, so if the TSH measurement is too high, the patient is diagnosed with hypothyroidism. The question is, what exactly is ‘too high’?

“There is considerable controversy about what the upper limit of normal for the range should be,” says Dr. Douglass Ross, Co-Director of the Thyroid Associates at Massachusetts General Hospital. Endocrinologists respond to the reference range uncertainty by simply using their best judgment. “I generally do not treat someone who feels ‘hypo’ but their TSH levels are normal and their antibodies are negative…but my definition of normal is much tighter than the normal range” says Dr. Stephanie Lee, an endocrinologist at Boston Medical Center. She also adjusts for age, treating young people for hypothyroidism if their TSH measures in the upper limit of the standard range.

Some argue that TSH reference ranges are too unreliable to be diagnostic. “When I was in medical school the TSH upper limit was 10,” says Dr. Ron Rothenberg,Vice President of the International Hormone Society in North and South America. “Now in most labs it’s like 5, 4.5. Most endocrine journals are saying 2.5. I think people feel the best when it’s less than 1.5. It’s a totally arbitrary number. But it’s set way too high. It lets a lot of people walk around hypothyroid.”

Within mainstream endocrinology, there is little debate when it comes time to write the prescription; a T4-only medication such as levothyroxine is almost always the choice. The idea is that when the T4 hormone enters the body, it converts to all the T3 the patient needs. “I prefer T4 because your body constantly, slowly converts T4 to T3 as needed, so the levels are very stable from minute to minute,” says Dr. Lee. “If you use T3 in addition to T4 or thyroid extract, the levels are very variable during the day.” While some occasionally prescribe T3 if T4 alone does not have the desired effect for the patient, few deviate often from synthetically-produced T4 medication.“(Levothyroxine) works beautifully…the biggest problem is they don’t take the pills regularly” says Dr. Lewis Braverman, a specialist in thyroid disorders and general endocrinology at Massachusetts General Hospital.

Some hormone therapists outside of mainstream endocrinology are less enthusiastic about T4-only medication being a catch-all hypothyroidism treatment. They say that patients feel best on a combination of T3 and T4, and some prescribe their patients desiccated thyroid (thyroid tissue extracted from pigs).“There has basically been a sort of assumption for the last 30, 40 years that all they need to do is get people T4 and their body will convert all of the T4 to T3 that they need and they’ll have perfect thyroid replacement. But that clearly does not work,” says Dr. Lindner. Some endocrinologists also acknowledge that not all patients’ bodies are equipped to convert T4 into the T3 that they need. “We know that certain people have genetic variance which make the conversion of T4 to T3 less efficient, and perhaps these are the patients who benefit from combination therapy,” says Dr. Kopp. However, endocrinologists tend to think of these patients as the exception, not the rule.

Endocrinologists continue to rely heavily on TSH tests for diagnosis despite a lack of consensus about the reference range. According to the 2014 “Guidelines for the Treatment of Hypothyroidism” published in the American Thyroid Association magazine Thyroid, levothyroxine is to remain the standard medication for treatment. But not even all mainstream endocrinologists think it’s a flawless system. “I think levothyroxine doesn’t mimic physiology perfectly,” says Dr. Ross. “People who take levothyroxine have slightly higher T4 and slightly lower T3 levels than normal.” Likewise, Dr. Kopp is skeptical that T4-only treatments are necessarily the best solution, believing that treatments with both T4 and T3 may have undiscovered potential. “As a clinician I can tell you that some people do feel better if they take combination therapy,” he says,“ but we don’t really know how to predict who benefits from combination therapy and who does not, and I think it is a part where we need more research to figure this out.”

With so much emphasis on blood tests, some non-mainstream thyroid doctors worry that endocrinologists are overlooking the most important source of information: the patient. “The old-time docs were clinicians and they would talk to the patients” says Dr. Jeffrey Dach, the founder of TrueMed MD. “We don’t have those guys any more.” But some endocrinologists hesitate when it comes to relying on vague symptoms such as fatigue and weight gain. “It’s really difficult to figure out whether their complaints are from their thyroid,” says Dr. Lee.

Amanda Zook understands firsthand that hypothyroidism is a complex condition. For the twenty years that she has been on medication, her TSH numbers have stayed in the normal range. Yet despite all the reassurances that nothing is wrong, Amanda knows better. “They don’t really have a way to test people when everybody is so different,” she says. [And] there’s no magic pill.”