Subclinical Hypothyroidism—Few Patients Benefit from Treatment

Findings from a pair of studies provide sufficient evidence to challenge any need to prescribe levothyroxine for mild hypothyroidism in nearly all patients except those planning a pregnancy.

With Mary Samuels, MD, James Hennessey, MD, and Deena Adimoolam, MD

Treating subclinical hypothyroidism has become accepted practice.  Despite any evident symptoms of mild disease, treatment has been deemed of value given an increased risk for cardiovascular disease based on findings from the Thyroid Studies Collaborative.1

While current guidelines indicate that more patients may be eligible for thyroid replacement therapy, mounting evidence refutes significant benefit to active management or any advantage in increasing levothyroxine dose in patients with mild or subclinical hypothyroidism.

Resist the temptation to treat subclinical hypothyroidism. While patients may perceive improvement in symptoms, changes their levothyroxine dose has little beneficial effect. Photo: 123rf

Actual and Perceive Responses to Differing L-T4 Doses 

A pair of randomized, double-blind studies,2,3 led by Mary Samuels, MD, professor of medicine and colleagues from the Oregon Health Sciences University in Portland, examined the lack of evidence in favor of levothyroxine replacement therapy in patients who demonstrated symptoms that may signal subclinical hypothyroidism but may also be attributed to other conditions.

In the first study,2  the researchers evaluated patients (n = 138) receiving levothyroxine (L-T4) for hypothyroidism and whose thyrotropin (TSH) to achieve the following ranges: 0.34-2.5; 2.52-5.6; and 5.61-12. Participants were assigned to one of three L-T4 treatment groups: unchanged dose, increased dose, and reduced dose, which were adjusted every six weeks over six months and followed to assess the following parameters:

  • Mood—Profile of Mood States and Affective Lability scale
  • Cognition—a measure of responses related to executive function such as memory recall, attention, and concentration based on tests administered by a research assistant
  • Quality of Life (QoL)—36-item short form health survey and Underactive Thyroid-dependent QoL questionnaire

TSH levels were checked every six weeks with levothyroxine doses adjusted as needed to maintain thyroid function levels in the normative ranges based on the most current treatment guidelines.At six months, affective characteristics were reassessed in all patients.2 There was no statistically significant difference in patient-reported symptoms, according to Dr. Samuels.  “Interestingly, patients seemed to prefer the dose of drug they thought was highest, regardless of the actual dose received, and whether or not there was any improvement in perceived symptoms based on surveys and testing,” Dr. Samuels told EndocrineWeb.

The second study followed the same group of patients, and examined energy expenditure, body composition, and body mass index (BMI) and assessed changes that occurred during treatment.3 While the researchers reported no statistically significant changes in either energy or body mass, the patients indicated feeling better at the dose they perceived was the highest prescribed.

Reconsider Treatment for Subclinical Hypothyroidism

“Over the years, we have been debating the issue of how to manage subclinical hypothyroidism,” said James Hennessey, MD, an associate professor at Harvard Medical School and director of endocrinology at the Beth Israel Deaconess Medical Center in Boston, Massachusetts.

Given that the most recent recommendations defining subclinical hypothyroidism effectively doubled the number of patients considered eligible for treatment, the findings arising from these two studies suggest that people without overt hypothyroid disease may be receiving treatment without merit.2,3  “This is very good work,” Dr. Hennessey told EndocrineWeb, “And this kind of research is very hard to do.”

Another reason for the apparent overtreatment may be that many physicians fail to heed age-related recommendations for treatment,4 said Dr. Hennessey.

“There are stark differences in the TSH range that has been regarded as normal across age groups, and what appears abnormal in a 30-year-old may be completely normal for a 70-year-old. For example, while a TSH of 2.5 mlU/L is great for a younger patient, a TSH of up to 6.0 mlU/L is considered fine for someone at 60, and once a patient is over 80 years old, levels of 6.5 to 7 mlU/L is deemed completely normal,” he said.

That is not to refute that an 80-year-old patient who reports that she is always cold, tired, and losing her hair may well benefit from levothyroxine replacement therapy, Dr. Hennessey said, but there are many other conditions, even the simple effects of aging, that may account for these generalized symptoms. In effect, starting a patient on even a low dose of levothyroxine may not prove beneficial, and may actually be counterproductive.  

“Age is only one of the factors that I rely on in evaluating whether or not a patient would benefit from thyroid replacement therapy,” said Deena Adimoolam, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai Hospital in New York City.

“We need to assess the patient based on her entire clinical situation —history of symptoms, physical examination, comorbidities, other meds—and lab values, specifically thyroid function tests, keeping in mind that these tests, specifically the TSH, will change with age in making a determination to treat or not to treat.”

Avoid Temptation to Treat, Focus on Educating Patients

A bigger problem, perhaps, is that the very patients who present with a self-diagnosis of hypothyroidism, insisting they need levothyroxine but need their physicians to resist these entreaties and offer alternatives, as appropriate.

“If TSH and T4 are at expected levels, don’t be afraid to tell a patient that the cause of the symptoms might be something else. It’s so easy to leap to hypothyroidism because it is easy to treat, but there are many other conditions which have similar symptoms,” said Dr. Hennessey.

“When a patient has confirmed subclinical thyroid function levels and requests thyroid replacement therapy, I spend the time to educate them on the risks associated with receiving thyroid replacement therapy and having thyroid hormone values that may become elevated,” said Dr. Adimoolam. “These include palpitations, anxiety, sweating, and cardiovascular risks such as arrhythmias, even heart failure.”

It is not unusual for patients to doctor shop, so Dr. Hennessey cautioned physicians to avoid relying on any diagnoses made by a previous provider. Dr. Adimoolam agreed, saying, “any new patient, regardless of how long since their original diagnosis, should be reassessed since life is not static. A change in clinical status, the addition of new or different medications and doses, and new life circumstances, such as pregnancy, may warrant a fresh evaluation of a patient’s thyroid medications and dosing.”

Physicians need to ask their patients how they felt before and after starting therapy, said Adimoolam. “Did it make a significant improvement in their lives? If it hasn’t, and they have subclinical thyroid disease, consider trailing them off of the medications for a finite period of time to see how they feel, and then reassess their thyroid function tests off of the medications.”

Dr. Hennessey indicated that it’s too early to change practice based on this new work. “Don’t be misled by non-specific symptoms when lab tests indicate patients are adequately treated, as they do not have the specificity to direct appropriate decisions.”

Both doctors hope for further studies of what levels of TSH merit treatment, and how age and other factors might change those treatment guidelines. “We need more data from long-term randomized controlled trials looking at patients who have been treated and NOT treated for subclinical hypothyroidism,” she said. “And we need to find out if there is truly any long-term benefit with mortality and quality of life.” 

Continue Reading:
American Thyroid Association (ATA) Spring 2017 Satellite Symposium: Hypothyroidism – Where are We Now?
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