Why Some Endocrinologists Oppose Natural Thyroid Drugsby Mary Shomon Patient Advocate
Editor's Note: This article is a part of an Op-Ed series, "Second Opinion," where patient experts and health writers share their take on current research, news, and trends in health and medicine. The views expressed in this article do not reflect the opinions or views of HealthCentral.com.
Why are endocrinologists so opposed to natural desiccated thyroid drugs (NDT)? Many endocrinologists not only refuse to prescribe these drugs to treat hypothyroidism, but some will not even treat patients who take or request NDT. Official groups and spokespeople sometimes vilify NDT, or promote levothyroxine over NDT treatment because: "NDT is not superior." What's going on, and what's driving this opposition? Let's take a look.
About natural desiccated thyroid
Natural desiccated thyroid - also known as thyroid extract, natural thyroid, and porcine thyroid - is a thyroid hormone replacement drug used to treat hypothyroidism. The brand names in the United States include Nature-throid, WP Thyroid, and Armour Thyroid. A generic NDT, NP Thyroid, is also available here. NDT is made from the desiccated (dried) thyroid gland of pigs. It contains thyroxine (T4), triiodothyronine (T3), and other thyroid hormones including T1, T2, and calcitonin.
Noted endocrinologist Wilmar Wiersinga, M.D., has written that hypothyroidism was an untreatable condition until the early 1890s, when patients started getting injections of thyroid extract derived from sheep. After that time, tablets were made from sheep thyroid as a treatment for hypothyroidism.
Eventually, NDT was introduced in the early 1900s as the sole hypothyroidism treatment on the market and has been available by prescription since that time. It is regulated by the U.S. Food and Drug Administrative (FDA), but because it was on the market before the creation of the FDA, the drug has not gone through the formal "new drug approval" (NDA) process and was instead "grandfathered" by the FDA.
In the 1950s, drug companies introduced levothyroxine, a synthetic form of T4, as an alternative to NDT. The launch of levothyroxine was accompanied by great fanfare and major marketing, casting NDT as an archaic, old-fashioned, and unreliable drug in comparison to the new, modern, and reliable levothyroxine. Still, levothyroxine was not required at that time to go through the NDA process. It too was grandfathered by the FDA, until 1997, when the FDA declared levothyroxine a "new drug" and called for NDA approval.
The drug companies making levothyroxine have become primary funding sources for thyroid and endocrinology associations, medical school educational programs regarding thyroid disease, research grants to groups and individuals studying levothyroxine, and have distributed many millions of dollars in free samples, lunches, and logo-imprinted gifts to promote the drug. There have also been whisper campaigns to doctors and pharmacies suggesting that NDT is "going off the market" or "being banned by the FDA." These whisper campaigns seem intent on discouraging physicians from prescribing NDT and discouraging patients from taking it.
Opposition to NDT
At present, many doctors believe, as stated by endocrinologist and osteopath Thomas Repas, D.O., FACP, FACE, CDE at the Endocrine Today blog, that "desiccated thyroid is antiquated therapy and should no longer be used."
This reflects the position of the most prominent association in the thyroid arena, the American Thyroid Association (ATA), a professional group of endocrinologists and researchers. The ATA regularly puts together panels to assess treatment options and release official treatment guidelines.
The ATA claims that levothyroxine is preferred because NDT is not "superior to" levothyroxine. As stated in the American Thyroid Association's 2014 Guidelines for the Treatment of Hypothyroidism:
"Although there is preliminary evidence from a short-duration study that some patients may prefer treatment using thyroid extracts, high-quality controlled long-term outcome data are lacking to document superiority of this treatment compared to levothyroxine therapy … levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine/liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes."
While still preferring and recommended levothyroxine, the European Thyroid Association (ETA) has a less dogmatic position. Their guidelines include the option for what they refer to as "experimental" use of combination T4/T3 therapy.
Studying T3 and natural desiccated thyroid
Because NDT is an FDA-regulated but not "FDA-approved" drug (as a result of the grandfathering of the drug), it is subject to severe restrictions on marketing and is often excluded from formularies, which limits sales and makes it less profitable. This means that manufacturers are unable to fund major research studies that could more fully evaluate the effectiveness of the drug.
Still, there has been some research supporting combination T4/T3 therapy, as well as NDT, and it's largely downplayed by the conventional thyroid world. For example, a major Danish study, published in 2009 in the European Journal of Endocrinology, found that T4/T3 combination therapy was superior to levothyroxine-only treatment, with measurable improvements in quality of life, and reductions in depression and anxiety, in patients taking combination treatment. The most important finding, however, was that 49 percent of the patients studied preferred the combination treatment. Only 15 percent preferred levothyroxine-only treatment.
Noted endocrinologist Dr. Wilmer Wiersinga, in discussing paradigm shifts in hypothyroidism treatment, described research conducted in the 1990s to evaluate thyroid function after surgery to remove the gland. According to Dr. Wiersinga, it's virtually impossible to achieve normal function on levothyroxine only, and that additional T3 is required.
Dr. Wiersinga believes that some patients have genetic differences that create that need for T3 in some patients. He has said:
"If further studies can identify this specific subgroup of hypothyroid patients, a third paradigm shift in the treatment of hypothyroidism might occur - perhaps heralding the use of personalized medicine in this setting."
One expert who is conducting further study is endocrinologist Antonio Bianco, M.D., Ph.D., of Rush Medical Center in Chicago and Bianco Lab. Dr. Bianco is studying genetic changes that could affect treatment effectiveness. According to Dr. Bianco, an issue known as genetic polymorphism in the type 2 deiodinase is found in a subset of people with hypothyroidism. This issue makes these patients less able to convert T4 into T3. For these patients, Dr. Bianco suggests that combination T4/T3 treatment may be needed to restore thyroid levels to the reference range, and relieve hypothyroidism symptoms.
NDT itself was the subject of an important federally-funded study conducted by Thanh D. Hoang, D.O., a staff endocrinologist at the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr. Hoang ran a randomized, double-blind, crossover study, evaluating the effectiveness of natural desiccated thyroid compared to levothyroxine for the treatment of hypothyroidism.
Dr. Hoang's study, published in 2013 in the Journal of Clinical Endocrinology and Metabolism, had results similar to the Danish study, reporting that:
49 percent of the patients studied preferred NDT treatment
19 percent of the patients studied preferred levothyroxine.
The patients taking NDT lost on average a total of three pounds, while those on levothyroxine had no weight loss.
In an interview with Endocrine Today, Dr. Hoang said:
"We didn't find any differences in the neurocognitive measurements between the two therapies ... We now know that once-daily desiccated thyroid extract is a safe alternative treatment for patients with hypothyroidism who are not satisfied with levothyroxine treatment. It's an option for them to try, and also desiccated can cause modest weight loss in these patients as well."
The American Thyroid Association's opposition to natural desiccated thyroid
Most endocrinologists take their direction from the ATA, which maintains that the guidelines and recommendation for levothyroxine and against NDT and combination T4/T3 therapy are evidence-based. There are, however, some disputable or questionable elements in their claims about NDT. On the ATA's information page on thyroid hormone treatment, they make the following statements (in bold), to which I've offered my rebuttal:
"Desiccated (dried and powdered) animal thyroid, now mainly obtained from pigs, was the most common form of thyroid therapy before the individual active thyroid hormones were discovered." - This is a fact.
"Since pills made from animal thyroid are not purified, they contain hormones and proteins that never exist in the body outside of the thyroid gland." - This is a fact but is misleading. Like an animal's thyroid gland, a human thyroid gland contains the same hormones and proteins that don't exist outside of the thyroid gland. Some experts theorize that this range of ingredients in NDT, including nutritional cofactors, may be a reason why it is preferred by some patients.
"… the amounts of both T4 and T3 can vary in every batch of desiccated thyroid, making it harder to keep blood levels right." - This is disputable. While there is some variation in individual batches, manufacturers are required to sample and test NDT. Quality control procedures ensure consistency in the amount of T4 and T3 in each batch and tablet.
"Desiccated animal thyroid is rarely prescribed today …" - This is disputable. Some statistics show that more than 2 million prescriptions are written each year for NDT drugs in the United States alone, and that number is growing each year.
"There is no evidence that desiccated thyroid has any advantage over synthetic T4." - This is disputable. The evidence shown by studies demonstrates that natural desiccated thyroid is a safe and effective alternative to levothyroxine. While studies to date have not shown an "advantage" as defined by endocrinologists, a significantly larger percentage of patients prefer NDT over levothyroxine-only treatment, as well as combination T4/T3 treatment, versus levothyroxine/T4-only. This assertion also dismisses the value of patient evidence-based findings.
While the unquestioned "superiority" of levothyroxine compared to "old-fashioned" NDT drugs has become accepted dogma in the endocrinology community, it's clear that the research does not support it. This raises a question: Are the ATA's "evidence-based" guidelines being unfairly influenced? Given what we know about the influence of drug companies, it's a valid question.
The ATA panels that create guidelines are supposed to operate without bias. At the same time, the ATA itself, as well as panel members, are frequent recipients of grants, funding, and financial support from drug companies whose products they are in a position to recommend. In fact, according to the 2016 ATA annual report, pharmaceutical company Abbvie, (formerly Abbott Labs) - manufacturer of the Synthroid brand of levothyroxine - is one of the ATA's top corporate donors. No manufacturers of NDT are major donors to the ATA or funding sources for its guidelines panel members.
Watchdog group ProPublica made it clear that money changes decision-making in doctors. Their 2016 study found that "the more money doctors receive from drug and medical device companies, the more brand-name drugs they tend to prescribe. Even a meal can make a difference." A British Medical Journal study also released in 2016 also showed that doctors who receive gifts from pharmaceutical companies are far more likely to prescribe or recommend those brand-name drugs.
Is pharmaceutical company support biasing the ATA and its guidelines panels to recommend levothyroxine and recommend against NDT? No one can say for sure, but it remains a pressing question.
Should you take NDT?
Clearly, larger and more comprehensive - and unbiased - research is needed comparing NDT to levothyroxine-only therapy. Until that research is conducted, it is unlikely that there will be any changes in the official guidelines for hypothyroidism treatment. Meanwhile, thyroid patients should be aware that NDT remains an option to levothyroxine for the treatment of hypothyroidism. NDT is FDA-regulated and legal to prescribe. Research also shows that NDT is as safe and effective as levothyroxine in many patients, and significantly more patients prefer NDT over levothyroxine to treat their hypothyroidism.