Subclinical Hypothyroidism Resolves Without Drugs in Many Older Adults, Study Shows

Located in the lower front part of the neck, the thyroid gland makes thyroid hormones — mainly thyroxine. Thyroxine plays a major role in growth and development in younger individuals and regulates energy use and other body functions in people of all ages. Thyroid-stimulating hormone (TSH), produced by the pituitary gland (a small gland at the base of the brain), prompts the production of T4, a form of thyroxine used by the body.[1]

Hypothyroidism (underactive thyroid) is characterized by elevated TSH levels in the blood. There are two types of hypothyroidism. The first type is overt hypothyroidism, which affects about 0.3% of Americans and is associated with low free T4 levels and certain symptoms (such as brittle hair, cold intolerance, constipation, dry skin, fatigue, muscle cramps and weight gain).[2],[3] The second type, subclinical hypothyroidism, is more common, affecting about 4.3% of Americans. People with subclinical hypothyroidism have normal free T4 levels and usually have no symptoms. Subclinical hypothyroidism is diagnosed based on laboratory test results.[4]

Clinical practice guidelines recommend that individuals with overt hypothyroidism be treated with levothyroxine (ERMEZA, EUTHYROX, LEVO-T, LEVOLET, LEVOXYL, SYNTHROID, THYQUIDITY, THYRO-TABS, TIROSINT, UNITHROID and generics), an oral, once-daily, synthetic form of thyroxine.[5] Once treatment is started, it usually is continued for life to maintain normal levels of thyroid hormone and to prevent complications, including poor development in children and infertility in adults. The Food and Drug Administration (FDA), however, has not approved levothyroxine to treat subclinical hypothyroidism. Thus, the use of levothyroxine in adults and older adults with subclinical hypothyroidism has been controversial.

For subclinical hypothyroidism, a wait-and-see strategy is recommended to monitor whether TSH levels normalize spontaneously over time.[6] Although this approach has been supported by several studies in adults, it remained insufficiently examined in older adults.

A large longitudinal multicenter European study, published in the February 2024 issue of The Journal of Clinical Endocrinology & Metabolism, found that spontaneous normalization of TSH levels occurred within about a year in about one-half of older adults with mild subclinical hypothyroidism. The findings support a wait-and-see approach to subclinical hypothyroidism in this population.

The new study[7]

Researchers analyzed data from two randomized, double-blind, placebo-controlled clinical trials with almost identical designs. The trials investigated the effect of levothyroxine treatment on older adults with subclinical hypothyroidism in the Netherlands, Ireland and the United Kingdom. From these trials, the researchers obtained data on subjects who did not receive levothyroxine and examined the extent of spontaneous resolution of this condition among them.

From the first trial, called TRUST, the researchers analyzed baseline (pretreatment) data for 2,335 community-dwelling subjects aged 65 or older (median age 73 years). From the second trial, called IEMO, the researchers analyzed follow-up data for 361 community-dwelling subjects aged 80 or older (median age 75 years) who received a placebo during the trial.

Almost all older subjects selected from both trials had mild subclinical hypothyroidism, defined as having at least one elevated TSH level (ranging from 4.6 to less than 10 milli-international units/liter [mIU/L]) and a normal free T4 level, during the baseline period. Because the subjects in the IEMO trial had at least two measurements of elevated baseline TSH levels that were at least three months apart, these subjects were considered to have persistent subclinical hypothyroidism.

After a median of one year of follow-up, TSH levels for 61% of older subjects in the TRUST trial had normalized without treatment. Likewise, after one year of follow-up, TSH levels for 40% of older subjects in the IEMO trial had returned to the normal range.

Overall, the researchers found that female sex and lower initial TSH level were independently associated with TSH levels returning to the normal range. Older female subjects were more likely than men with the same initial TSH levels to have their hormone levels return to the normal range. Specifically, older women who had a baseline TSH level of 5 mIU/L had a 73% chance of reaching normal TSH levels and those with a baseline TSH level of 10 mIU/L had a 20% chance of reaching normal TSH levels. In contrast, for older men, the chance of TSH normalization decreased from 76% when their baseline level was 5 mIU/L to just 7% when their baseline TSH level was 10 mIU/L.

Other factors that were independently associated with TSH levels returning to the normal range included an absence of thyroid peroxidase antibodies, higher normal initial T4 level, younger age and TSH measurements in the summer.

At present, clinicians often obtain two TSH measurements about three months apart before considering the initiation of levothyroxine treatment in patients with subclinical hypothyroidism. The new study supports a change in this practice: obtaining three TSH measurements several months apart. If this change in practice is adopted, fewer older adults would be started on levothyroxine therapy, according to findings from the new study. This also would mean that complications of overtreatment with levothyroxine (such as anxiety, osteoporosis [bone loss], palpitations, rapid heart rate, sweating, tremors and weight loss) could be avoided.

What You Can Do

If your clinician determines that you have subclinical hypothyroidism based on a single TSH test, discuss with them the approach of having two additional TSH tests that are several months apart before considering thyroid hormone therapy. Eat a balanced diet that includes essential nutrients (such as Brazil nuts, kale and spinach) to support your thyroid health.[8]

When treatment is needed, opt for levothyroxine. Do not use liothyronine or liothyronine-containing drugs as a maintenance therapy for hypothyroidism, because there is no long-term evidence that supports their effectiveness or safety relative to levothyroxine-only treatment.[9]

Do not use thyroid extracts (ARMOUR THYROID, NATURAL THYROID and others), which are not regulated by the FDA.[10] Thyroid extracts may have inconsistent dosage.
 

References

[1] American Thyroid Association. Thyroid function tests. 2019. https://www.thyroid.org/wp-content/uploads/patients/brochures/FunctionTests_brochure.pdf. Accessed May 30, 2024.

[2] Simon C, Weidman-Evans E, Allen S. Subclinical hypothyroidism: To treat or not to treat? JAAPA. 2020;33(5):21-26.

[3] Hollowell J, Staehling N, Flanders W, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489-499.

[4] Ross D. Subclinical hypothyroidism in nonpregnant adults. UpToDate. April 2024.

[5] Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-1751.

[6] Calissendorff J, Falhammar H. To treat or not to treat subclinical hypothyroidism, what is the evidence? Medicina. 2020;56(1):40.

[7] van der Spoel E, van Vliet NA, Poortvliet RKE, et al. Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults. J Clin Endocrinol Metab. 2024;109(3):e1167-e1174.

[8] Zhou Q, Xue S, Zhang L, Chen G. Trace elements and the thyroid. Front Endocrinol. 2022;13(October 24):904889.

[9] Oral treatments for hypothyroidism. Worst Pills, Best Pills News. November 2016. https://www.worstpills.org/newsletters/view/1067. Accessed May 30, 2024.

[10] Food and Drug Administration. Older therapies aren’t necessarily better for thyroid hormone replacement. January 4, 2023. https://www.fda.gov/consumers/consumer-updates/older-therapies-arent-necessarily-better-thyroid-hormone-replacement. Accessed May 30, 2024.