Why 23 Million Americans on Thyroid Hormone Is a Concern
A doctor warns about the impact of overprescribing
Seven percent of individuals in the United States are prescribed levothyroxine, a synthetic version of the hormone, thyroxine, which is the main chemical produced by the body’s thyroid gland. The supplemental hormone consistently ranks among the top three prescriptions in the U.S. each year. In the past few days working at the hospital, I noted that one-sixth of the patients I saw were taking levothyroxine. This finding wasn’t terribly surprising to me and seemed like a fairly average sampling based on prior experience.
What has been surprising to me, however, is the mounting evidence indicating that most levothyroxine prescriptions, as much as 90% according to some, are completely unnecessary. If you’re doing the math in your head, then, yes, that implies 20 million Americans may be affected by this epidemic of overprescription.
“Some people really need this medicine, but not the vast majority of people who are taking it.” explains Dr. Juan Brito, an endocrinologist, or hormone specialist, at the Mayo Clinic. Clear indications to supplement adults with thyroid hormone may include thyroid cancer, previous thyroid surgery, abnormal pituitary gland function, or circumstances surrounding pregnancy. The ‘vast majority’ to whom Dr. Brito refers carry none of these diagnoses, but instead have a condition called subclinical hypothyroidism (SCH).
According to experts like Brito, SCH is more of a lab abnormality than an illness. Brito served on an international panel of thyroid specialists who published in 2019 that, “For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid-related symptoms, including depressive symptoms, fatigue, and body mass index (BMI).”
The problem isn’t unique to the U.S. “There’s an increasing tendency to treat subclinical hypothyroidism in many countries, including Canada,” describes Deric Morrison, an endocrinologist at St. Joseph’s Hospital in Ontario. “But the evidence is now suggesting for most of those people, treating that [lab] number doesn’t make them better.”
A 60-second primer on the thyroid
There are many lab and imaging tests related to the thyroid gland, but doctors use two main blood tests to assess a patient’s thyroid function. These are thyroid-stimulating hormone (TSH) and thyroxine (T4).
TSH is made in the pituitary gland. Its purpose is to signal the thyroid gland to produce thyroid hormones — primarily thyroxine (T4) but also triiodothyronine (T3). These thyroid hormones (T3 & T4) then go on to affect many aspects of the body’s metabolic function. When T3 & T4 levels are too high, patients can suffer from symptoms of anxiety, sweating, tremor, diarrhea, weight loss, and hair loss. Conversely, patients may develop depression, fatigue, cold sensitivity, weight gain, constipation, and heavy menses when thyroid hormone levels are too low.
The body possesses natural feedback loops that serve to regulate these hormones. When T3 & T4 levels are elevated, the pituitary senses this and responds by producing less TSH. The opposite occurs when T3 & T4 levels are too low — TSH production goes up. Unfortunately, there are numerous adverse medical conditions can throw this intricate system out of balance.
The most common cause of hypothyroidism (i.e. low T3 & T4) among industrialized nations is an autoimmune disease called Hashimoto’s thyroiditis. Other causes include iodine deficiency (the most common cause worldwide), surgical removal of the thyroid, radiation, medications that damage the thyroid, and rare diseases that can infiltrate the thyroid gland such as amyloidosis and Riedel thyroiditis. In addition, problems with the pituitary gland or hypothalamus in the brain can lead to what is called central hypothyroidism.
When the thyroid isn’t making enough thyroid hormone, except in the rare case of central hypothyroidism, the body’s TSH level will become elevated because the pituitary is trying, albeit unsuccessfully, to trigger the thyroid to produce more thyroid hormone. If the TSH is elevated while the T4 level is low, this is called overt hypothyroidism which occurs in only 0.3–0.8% of the U.S. population and should be treated with a supplemental thyroid hormone like levothyroxine.
On the other hand, if the TSH is elevated, but the T4 level remains normal, this is called subclinical hypothyroidism (SCH). So now we’ve come full circle back to the condition, or lab abnormality as some might prefer, driving this controversy over excessive treatment with levothyroxine.
More than a hypothesis
For years many practitioners have suspected widespread overprescribing of levothyroxine, and a study published in JAMA this year by Dr. Brito and colleagues provided traction to the claim. Their review of data from over 50,000 patients started on levothyroxine revealed that only 8.4% were treated for overt hypothyroidism while 61% were treated for SCH. Even more astonishingly, 30.5% of the cohort were started on levothyroxine despite having completely normal thyroid function studies. In other words, over 90% of this large study population received supplemental thyroid hormone without a clear indication.
Data suggests lack of benefit in many cases
Overprescribing might not be such a problem as long as patients experience some degree of benefit from the treatment, but do they in this case? In a recent editorial also published in JAMA, authors William Silverstein, MD and Deborah Grady, MD, MPH commented, “Randomized clinical trials have repeatedly demonstrated that treatment of SCH with levothyroxine does not relieve symptoms potentially associated with hypothyroidism…including quality of life, handgrip strength, cognitive function, blood pressure, weight, and BMI.”
Such trials are the reason many clinical practice guidelines recommend against treating SCH in patients whose lab values are only slightly abnormal. Although there is some variance among different laboratories, a normal TSH is typically in the range of 0.5–4.5 milli-international units per liter (mIU/L). Yet the American Thyroid Association and the American Association of Clinical Endocrinologists recommend withholding levothyroxine for SCH unless the TSH is greater than 10 mIU/L.
For those wishing to avoid unnecessary treatment, it’s easy to see the value in such guidance. Even if left untreated, TSH levels for 62% of patients with SCH spontaneously normalize within five years, and only 2–5% of these patients each year go on to develop overt hypothyroidism.
A 2018 prospective study published in the journal, Thyroid, followed a group of nearly 300 patients taking levothyroxine who were not known to have overt hypothyroidism. Upon discontinuing the drug, investigators found that 61% of patients continued to have normal thyroid hormone levels even 6–8 weeks later.
Dr. Anna Sawka, an endocrinologist who has served on the American Thyroid Association’s Thyroid Replacement Task Force commented on the study. “A substantial proportion of individuals taking levothyroxine in whom the original indication for treatment is unclear, may not need to be taking this hormone.” Sawka noted a few exceptions adding the caveat that, “These findings may not be applied to patient groups excluded from the study (e.g. patients with thyroid surgery, women planning to get pregnant, and others).”
First, do no harm
While strong scientific evidence demonstrates a lack of benefit from levothyroxine in patients with SCH, isn’t thyroid hormone pretty harmless? If the worst thing that can happen is the medication simply not working, why not give it a try?
Silverstein and Grady highlight a number of flaws with this approach reporting “An association between long-term levothyroxine therapy and increased risk of cardiovascular disease, cardiac dysrhythmias, osteoporosis, and fractures.”
In addition, they cite the cost of unnecessary pills and bloodwork as an excess financial burden to the patient and an already strained healthcare system. Excessive prescribing contributes to polypharmacy which, in turn, increases the likelihood of adverse drug interactions. Because levothyroxine should be administered on an empty stomach apart from pills containing calcium or iron, adding it to a patient’s drug regimen interferes with daily routines and raises the risk of nonadherence to other medications.
“Once levothyroxine treatment is initiated for SCH,” Silverstein and Grady expound, “The majority of patients [90% according to one study] will continue therapy for life.” Perhaps the greatest potential for harm is that unnecessary treatment of SCH may obfuscate the true underlying cause of a patient’s symptoms. Because the signs of hypothyroidism are non-specific and often observed in other conditions, falsely attributing a patient’s symptoms to hypothyroidism can easily lead to a missed diagnosis.
All natural
While the harms of unnecessary levothyroxine are becoming more apparent, some wonder if treatment with natural, as opposed to synthetic, thyroid supplementation such as thyroid extracts could prove worthwhile.
At this time, the American Thyroid Association recommends against treatment with thyroid extracts because of a lack of data on its efficacy and safety, but trials seeking to clarify this issue are on the horizon. In fact, a study published earlier this year suggested that a combination of thyroid extract and levothyroxine may be as effective as levothyroxine alone at treating symptoms of hypothyroidism.
Taking action
If you or a loved one happen to have SCH and are being treated with levothyroxine, this story is not an admonishment to discontinue the drug, but rather a reminder to continue the conversation with your doctor or other medical provider about how such treatment applies to your unique situation.
As Dr. Sawka cautions, “It is not advisable for patients to stop thyroid medication on their own, without consulting a healthcare practitioner. Patients in whom levothyroxine is discontinued still need to be followed to determine if they may eventually need to go back on levothyroxine at some point.”
If concerns remain, consider requesting a referral to an endocrinologist. As part of their job, these experts maintain a comprehensive understanding of the latest research and guidelines on multiple hormonal systems including the thyroid. As of 2018, only 12% of patients treated for SCH were evaluated by an endocrinologist implying that this group of specialists are unlikely to be contributing to the problem of overprescribing levothyroxine but are, in fact, a valuable resource to bring about a solution.
As a physician, this topic reminds me how easy it can be to add just one more medication to a patient’s list without considering the downstream consequences, whereas the process of deprescribing is often more laborious. According to Dr. Brito, “We have to come up with different approaches to symptoms that have nothing to do with levothyroxine.” In the case of SCH, clinicians must resist the temptation to be satisfied with a quick and easy fix that may leave the patient reassured for the moment but prove detrimental in the long run.
Brito continues, “I try to explain to patients that it’s very unlikely that subclinical hypothyroidism would be driving significant symptoms like fatigue, weight gain, and hair loss.” Providers like Dr. Brito recognize that delivering high-quality care means being honest with patients even if it requires lengthy discussion and additional effort to explore alternate causes of their symptoms.
Like most doctors, I love solving problems. Whenever I arrive at a solution quickly, it feels as though I must surely be providing great care for my patient. Indeed, that may sometimes be the case, but if the simple and fast solution isn’t the correct one, I’m doing a disservice to that individual. As more patients and prescribers realize the advantages of a less-is-more approach, it is my hope that more humans will experience the simple pleasure of one less tablet in their pill box.
Dr. Stapler practices adult and pediatric hospital medicine in Billings, Montana, USA, and loves every minute of it (usually). Check out more of his work and follow him at bostapler.medium.com.
