New Guideline Recommends Against Thyroid Hormone Treatment for Most Adults With Mildly Underactive Thyroid

The thyroid gland makes hormones — most importantly thyroxine — that are necessary for growth and development in children and for regulating energy levels and metabolism in people of all ages. Free T4 is the active form of thyroxine used by the body. T4 production is stimulated by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland, a pea-sized structure in the brain.

There are two types of underactive thyroid (hypothyroidism). The first is overt hypothyroidism, in which the blood levels of free T4 are low and those for TSH are high.[1] This condition typically is associated with certain symptoms, including fatigue, muscle cramps, cold sensitivity, dry skin, voice changes, constipation and weight gain.[2] Other symptoms may include forgetfulness, slowed thinking, weak muscles, puffy eyes, anxiety and depression. Importantly, all of these symptoms are not specific for hypothyroidism and can occur with many other conditions.

The second type, subclinical hypothyroidism, is a mild form of underactive thyroid, in which the levels of free T4 are within the normal range but TSH levels are elevated. Patients with subclinical hypothyroidism may not experience any of the symptoms associated with overt hypothyroidism. Therefore, the condition is usually diagnosed solely based on the results of thyroid function tests.

Whereas clinical practice guidelines for overt hypothyroidism consistently recommend thyroid hormone therapy for affected individuals, those for subclinical hypothyroidism have been inconsistent on whether such treatment is necessary. As discussed in the November 2017 issue of Worst Pills, Best Pills News, guidelines at that time recommended thyroid hormone treatment for adults with blood TSH levels that are higher than 10 milli-international units/liter (mIU/L) (the normal blood TSH level range is approximately 0.4 to 4.0 mIU/L).[3]

This article updates key parts of our recommendations for treating subclinical hypothyroidism as a result of a new evidence-based guideline that strongly recommends against thyroid hormone treatment for this condition in most adults who are considering such therapy, because there are no important benefits from such treatment.[4]

The new guideline was developed by a group of international experts with no declared financial conflicts of interest and was published online in the BMJ (formerly called the British Medical Journal) on May 14 as part of the journal’s rapid recommendation initiative.

Evidence supporting the new guideline

The new guideline was based on results from a 2018 systematic review of 21 randomized clinical trials involving nearly 2,200 adult subjects that was published in the Journal of the American Medical Association[5] (including a large trial called “TRUST” that was limited to subjects aged 65 or older and was published in the New England Journal of Medicine in 2017[6]). These trials compared the effect of initiating thyroid hormone treatment with that of no treatment or placebo in nonpregnant adults with subclinical hypothyroidism.

Both the systemic review and the TRUST trial, as well as an additional analysis (conducted by the new guideline developers) that excluded subjects from the TRUST trial, consistently showed no important benefits from thyroid hormone treatment in adults with subclinical hypothyroidism. Specifically, there was little to no difference in terms of general quality of life, thyroid-related symptoms, depressive symptoms, fatigue, cognitive function, muscle strength or body mass index (a measure of body fat) between adults with subclinical hypothyroidism who had thyroid hormone therapy and those who received no therapy or a placebo. The guideline developers characterized the strength of this evidence as “high” in the elderly and as “moderate-to-high” in adults younger than 65.

Although there is only low-quality evidence that taking thyroid hormones may be associated with an increased risk of death or cardiovascular events (including stroke or heart attack), these risks cannot be ruled out because only one trial looked at the harm of treatment with these hormones. Additionally, the guideline developers were concerned about the burden of lifelong treatment. They also noted that levels of TSH, a key criterion for clinical hypothyroidism, fluctuate and may revert to normal without treatment in some people.

The new recommendation[7]

Due to the lack of important benefits and the possibility of harm, the new guideline made a “strong” recommendation against using thyroid hormones in most adults with subclinical hypothyroidism (as confirmed based on at least two consecutive thyroid function tests) who are considering this treatment.

Notably, this no-treatment recommendation applies to adults with or without mild-to-moderate symptoms of subclinical hypothyroidism. It may not apply to individuals with severe symptoms or to those under the age of 30 because few of these individuals were represented in the reviewed studies. The recommendation also may not apply to patients who are already taking thyroid hormones (because they were not represented in the reviewed studies). Instead, these patients should be evaluated on an individual basis to determine whether they should continue to receive thyroid hormones.

The recommendation also does not apply to individuals with TSH levels above 20 mIU/L (because they may border overt hypothyroidism) or to women who are trying to become pregnant or who are at risk of unplanned pregnancy (because some evidence suggests that a lack of treatment increases the risk of adverse outcomes to the mother and the baby).

Importantly, the guideline recommends regular doctor visits and blood tests for patients with subclinical hypothyroidism who are not treated with thyroid hormones to monitor the progression of the condition or its resolution.

What You Can Do

If your doctor has determined that you have subclinical hypothyroidism, discuss this article with him or her, particularly if you are an adult considering thyroid hormone therapy.

You generally do not need to take thyroid hormones for your condition unless your TSH levels are above 20 mIU/L, you have severe symptoms or you are a woman who is trying to become pregnant or are at risk of becoming pregnant. However, you still need to see your doctor on a regular basis to monitor the progression or resolution of your subclinical hypothyroidism.

If you do need thyroid hormone replacement therapy for any type of hypothyroidism, opt for levothyroxine (EUTHYROX, LEVO-T, LEVOXYL, SYNTHROID, THYRO-TABS, TIROSINT, UNITHROID) tablets — the standard drug for underactive thyroid.[8] Try to keep using the same levothyroxine formulation. Take the drug at least 30 minutes before breakfast and do not take it within four hours of taking any antacids or supplements that contain calcium or iron.[9] Never stop taking the drug, skip a dose or adjust your dose without medical supervision. To learn more about thyroid hormone drugs, see the November 2016 issue of Worst Pills, Best Pills News.
 

References

[1] American Thyroid Association. Hypothyroidism. 2017. http://www.thyroid.org/wp-content/uploads/patients/brochures/ata-hypothyroidism-brochure.pdf. Accessed September 8, 2019.

[2] Bekkering GE, Agoritsas T, Lytvyn L, et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019;365(May 14):l2006. doi:10.1136/bmj.l2006.

[3] Subclinical hypothyroidism: When to treat. Worst Pills, Best Pills News. November 2017. /newsletters/view/1162. Accessed September 8, 2019.

[4] Bekkering GE, Agoritsas T, Lytvyn L, et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019 May 14;365:l2006. doi:10.1136/bmj.l2006.

[5] Feller M, Snel M, Moutzouri E, et al. Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: A systematic review and meta-analysis. JAMA. 2018;320(13):1349-1359.

[6] Stott DJ, Rodondi N, Kearney PM, et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017;376(26):2534-2544.

[7] Bekkering GE, Agoritsas T, Lytvyn L, et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019;365(May 14):l2006. doi:10.1136/bmj.l2006.

[8] Oral treatments for hypothyroidism. Worst Pills, Best Pills News. November 2016. /newsletters/view/1067. Accessed September 8, 2019.

[9] AbbVie Inc. Label: levothyroxine (SYNTHROID). May 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e11ad30-1041-4520-10b0-8f9d30d30fcc. Accessed September 9, 2019.