“These meta-analyses provide important information about potential risks from untreated subclinical thyroid dysfunction and support a dose-response relationship between thyroid-stimulating hormone (TSH) concentrations at either extreme and an increased risk for cardiovascular events and death,” Drs Cappola and Cooper wrote. “They also support potential serum TSH thresholds for increased risk of less than 0.45 and greater than 7 mIU/L and more confident thresholds of less than 0.1 and greater than 10 mIU/L, although the benefits and harms of treatment at these thresholds have not been defined in [randomized controlled trials].”

“More severe forms of hypothyroidism can result in worsening of heart function and heart failure, If there is suspicion that hypothyroidism is the primary reason for heart failure, treatment with thyroid hormone supplementation should definitely be started,” said Josef Stehlik, MD, MPH, medical director of the heart transplant program and associate professor of medicine at the University of Utah.


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Jamil B. Alkhaddo, MD, an endocrinologist specializing in diabetes, thyroid, and adrenal conditions in adult patients with the Allegheny Health Network Center for Diabetes and Endocrine Health, said there are few if any large-scale studies exploring whether or not to treat subclinical patients, and evidence from smaller studies isn’t definitive.

“We have data from analysis from pooled patients or meta-analysis of other small studies,” he said. “We know for sure right now that with thyroid-stimulating hormone, TSH, if it’s above 10 mIU/L, we treat the patient, even those with subclinical hypothyroidism.”

Thyroid Hormone as Therapy?

If elevated levels of TSH are associated with poorer cardiac outcomes, could physicians use thyroid hormone to treat or prevent heart disease? Anthony Martin Gerdes, PhD, professor and chair of biomedical sciences at the New York Institute of Technology, has spent decades researching that question. After nearly 40 years of animal studies, he is convinced that T3 hormone can be a huge boon to cardiac patients.

“I would like to see clinical studies that take groups of patients with heart disease or heart failure who have borderline low thyroid dysfunction and treat them with a tiny dose of T3 where the effect may be so rapid in responders that effects from improved coronary blood flow may be detected within an hour or so,” he said. “Why not do those studies with a dose that’s so low that you know it’s not going to be toxic? However, what is sorely needed is a serum biomarker for cardiac tissue hypothyroidism to better identify patients who may benefit from treatment.”

Earlier this year, Dr Gerdes and Kaia Ojamaa, PhD, an associate investigator for the Lab for Molecular Cardiovascular Research at the Feinstein Institute for Medical Research and an associate professor of Molecular Medicine at Hofstra Northwell School of Medicine, published a paper in Comprehensive Physiology suggesting there could be a role for thyroid hormone therapy in cardiology, noting that “a safe TH treatment/monitoring protocol has now been confirmed in animals with heart diseases leading to HF.”9

“There is a large body of clinical evidence suggesting that low [thyroid hormone] function is common in cardiac patients and treatment offers many potential benefits. The extent of the problem is likely underappreciated by results from serum TH tests,” Drs Gerdes and Ojamaa wrote. “A substantial number of studies of patients with heart disease and animal models have shown that TH treatment enhances cardiovascular hemodynamics, gene expression, and coronary blood flow. This cumulative body of data lends support to the benefit of treating patients with chronic heart disease and possibly those with acute ischemic injury with [thyroid hormones].”

The problem, said Michael Bristow, MD, PhD, a cardiologist and professor of Medicine at the University of Colorado, is that results in animal studies are a far cry from results in human studies.

“It works pretty well in rats, but the studies that have been done in humans have not been very impressive,” he said.

Dr Stehlik was more skeptical. There are no large-scale studies exploring this question and the results from smaller studies haven’t been encouraging.

“Smaller studies have not confirmed beneficial effect of the thyroid hormone,” Dr Stehlik said. “Also, high levels of thyroid hormone can be detrimental to heart function, such that supplementing thyroid hormone in a patient with normal thyroid level could potentially increase the risk to the patient.”

Dr Bristow did not completely dismiss the idea out of hand, however. He has his own long research history and said there are at least potential avenues worth exploring.

“There are a couple of different types of thyroid hormone receptor in the heart,” he said. “I’m not saying that this is something that shouldn’t be pursued. I’m just saying that the clinical data so far, the clinical studies that exist—and there are 3 or 4 of them—are unimpressive.”

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References

  1. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116:1725-1735. doi:10.1161/CIRCULATIONAHA.106.678326.
  2. Rodondi N, den Elzen WPJ, Bauer DC. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304:1365-1374.
  3. Chaker L, van den Berg ME, Niemeijer MN, et al. Thyroid function and sudden cardiac death: a population-based cohort study. Circulation. 2016;134:713-722. doi: 10.1161/CIRCULATIONAHA.115.020789.
  4. Higher thyroid hormone levels linked to sudden cardiac death [press release]. Dallas, TX: American Heart Association/American Stroke Association Newsroom; September 6, 2016. http://newsroom.heart.org/news/higher-thyroid-hormone-levels-linked-to-sudden-cardiac-death. Accessed October 26, 2016.
  5. LeFevre ML. Screening for thyroid dysfunction: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;162:641-650. doi: 10.7326/M15-0483.
  6. Cappola AR, Cooper DS. Screening and treating subclinical thyroid disease: Getting past the impasse. Ann Intern Med. 2015;162:664-665. doi: 10.7326/M15-0640.
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  8. Gencer B, Collet TH, Virgini V, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012;126(9):1040-1049.
  9. Gerdes AM, Ojamaa K. Thyroid hormone and cardioprotection. Compr Physiol. 2016;6:1199-1219. doi: 10.1002/cphy.c150012.