Hillary Clinton Puts Hypothyroidism Options in the Spotlight

Nancy A Melville

October 17, 2016

While news of Hillary Clinton's recent bout with pneumonia dominated the release of her health report, the less well-known issue of her hypothyroidism is notable not only for the treatment she receives but for how it connects her with some intriguing chapters in past presidencies.

According to the report, issued last month by Clinton's physician, Lisa Bardack, MD, Clinton has been treated for hypothyroidism and has "remained stable for many years on Armour thyroid [Forest Labs] to treat her hypothyroidism."

While hypothyroidism isn't at all uncommon, particularly in women over the age of 60 (Clinton is 68), the treatment — a brand of natural desiccated thyroid, a porcine thyroid extract — is decidedly less conventional than the current standard of care, a synthetic thyroxine called levothyroxine (L-T4).

Use of thyroid extract, which dates back to the 19th century, was long the only choice for hypothyroidism treatment before falling out of favor with the advent of L-T4 therapy and strong evidence showing serum levels of thyroid hormones were no different between those treated with L-T4 alone and normal controls, whereas a combination of T4 and tri-iodothyronine, also known as T3, resulted in nonphysiologic elevations in T3. Thyroid extract such as Armour provides a combination of both T4 and T3.

An Older Therapy; but If It Ain't Broke, Don't Fix It?

Angela M Leung, MD, an assistant professor of medicine at the University of California, Los Angeles David Geffen School of Medicine, told Medscape Medical News why the current standard of care is levothyroxine.

"The American Thyroid Association (ATA) currently recommends that levothyroxine alone be used for the routine treatment of the majority of cases of hypothyroidism, as high-quality controlled long-term outcome data regarding desiccated thyroid-extract use are lacking."

She noted that "in addition, there may be safety issues, primarily related to cardiac arrhythmias and bone health, associated with desiccated thyroid-extract use."

And James V Hennessey, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, told Medscape Medical News that a key concern with desiccated thyroid in the past was an unreliable balance of T4 and T3 from product to product and batch to batch.

"Although modern extract products are adjusted to ensure predictable amounts of L-T4 and L-T3, the 4:1 ratio of T4 to T3 is quite dissimilar to the 14:1 balance in humans," he explained.

"It turns out that when thyroid extract is ingested it can lead to spikes in T3 levels, which go well above what's generally considered physiologic."

Nevertheless, many patients report simply feeling better when treated with thyroid extract or combination T4/T3 therapy, and debate about L-T4 monotherapy vs a combination of T4 and T3 has long been a controversial subject.

The ATA and US Endocrine Society each acknowledge the use of combination therapy is reasonable when patients fail to respond to monotherapy, with the ATA having removed a previous recommendation that desiccated thyroid extract not be used. However, the group still underscores evidence of L-T4's superiority.

While natural thyroid extract and an emphasis on T3 is largely favored in the complementary-medicine community, Dr Hennessey — noting that he is not in a position to comment specifically on Clinton's health — said it is not at all uncommon for endocrinologists to see patients of Clinton's generation who are being treated with Armour.

Indeed, Dr Hennessey recently published a paper detailing the history and current use of thyroid extracts (Endocr Pract. 201;21:1161-1170).

"I encounter this in clinical practice, and it could simply be that the patient was started on thyroid extract decades ago, before levothyroxine became the standard of care, and as long as their thyroid levels are normal and they're not being overdosed on T3, I might very well leave it alone."

Interestingly, another candidate in Clinton's generation — her Democratic ticket opponent, Vermont Senator Bernie Sanders, who is 76 — also was described in his health report from Senate physician Brian P Monahan, MD, as receiving treatment for hypothyroidism, yet, in perhaps an unexpected twist, Sanders is in fact the one treated with the more conventional approach — levothyroxine.

Again, such a choice could simply reflect a later diagnosis, when L-T4 became standard, Dr Hennessey speculated.

In terms of how hypothyroidism could affect one's ability to lead, if untreated, the doctors say symptoms could prevent function below the top of one's game, such as fatigue and feeling foggy-headed. But treated to normal thyroid levels, as is reportedly the case with Clinton, those symptoms should alleviate.

Nevertheless, some cases can be tougher than others, and efforts to line up normal thyroid levels with a resolution of symptoms can be an ongoing challenge.

"In most all patients, the thyroid-function tests are normalized, but symptoms can persist," Dr Leung explained.

"A further problem is that hypothyroid signs and symptoms are classically so nonspecific that resolution of biochemical hypothyroidism may not necessarily be associated with the complete resolution of clinical clues suggestive of hypothyroidism.

"This is an issue that affects a large proportion of the population, and there is active and ongoing research in this field to more clearly understand how thyroid-function lab tests can be better translated into clinical features of hypothyroidism," she noted.

Did Hyperthyroidism Cost Bush Reelection?

In a look back at thyroid disease in the White House, another notable case is that of the overactive thyroid of President George HW Bush, which could possibly have cost him his reelection.

The incident was considered a true medical mystery — in the course of little more than a year, the senior President Bush and his wife, Barbara, were coincidentally each diagnosed with not an underactive but overactive thyroid, specifically Graves' disease, and even the family's dog, Millie, developed lupus, also an autoimmune disorder.

Barbara Bush said in a TV interview that her thyroid "just went wacko" — she'd lost 18 pounds without dieting before the diagnosis and had symptoms of swollen eyes that are consistent with Graves' ophthalmopathy.

Mrs Bush chose to publicly discuss her illness to bring attention to the issue of thyroid disorders.

With Graves' disease well-known to be hereditary but not contagious, the cases were considered so unusual that the Secret Service launched an investigation of the tap water at the White House, as well as Camp David, Kennebunkport, and the vice presidential mansion at the National Observatory in Washington, where the family lived during Mr Bush's terms as vice president from 1981 to 1989. Results of the investigation were never reported.

The most damaging fallout for President Bush, however, may have been not from the illness, but from the treatment.

Both the president and Mrs Bush received the standard treatment of radioiodine therapy, which can send patients plummeting down from an anxious, hyperthyroid state to a possibly sluggish, underactive thyroid state before settling back into normal function.

Dr Hennessey — who wasn't Bush's endocrinologist but who practiced at the time at Walter Reed Hospital in Washington, DC, where the president was treated — said discussion back then suggested that Bush indeed suffered the effects of the dramatic swing in thyroid function.

"The word was that when he was thyrotoxic and had an overactive thyroid, Bush was sort of nervous and anxious and his heartbeat was discovered to be irregular after jogging at Camp David," he explained.

"But compared with this hyper state, which he had been experiencing for a while, the treatment likely caused his thyroid to course down through normal and maybe a little to subnormal for a while, before the supplementation with thyroid hormone was optimally effective.

"Some people speculated that it was this transition that led to a slump in his political activity later in that campaign and may have even played a role in not having him as energized as some in his party wanted. It turned out he didn't win reelection."

Dr Hennessey has previously acted as a scientific consultant for Veracyte, Akrimax Pharma, Abbott Labs, and Sandoz Pharma and served as the content director at PriMed (2013 and 2015). Dr Leung had no relevant financial relationships.

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