It is commonly thought that thyroid dysfunction, especially hypothyroidism, has a high prevalence in older adults — possibly as high as 25%. But there is not consensus regarding what constitutes normal thyroid function in this population.

“The textbook description of hypothyroidism in older adults is that it is highly prevalent, especially among older women — a phrase that’s been around for at least 50 years,” James Hennessey, MD, associate professor of medicine at Harvard Medical School and director of clinical endocrinology at Beth Israel Deaconess Medical Center, both in Boston, told Medscape Medical News. “But when you go back and dissect this statement, it’s likely a misnomer and it’s misleading.”

One reason for the misperception of the condition’s prevalence in older adults is that the term hypothyroidism lumps together its overt and subclinical types, said Risheng Xu, DO, assistant professor of medicine, Baylor College of Medicine, Houston.

“But in this age group, ‘subclinical hypothyroidism’ may not be a real entity, but rather a nomenclature we artificially created,” he told Medscape Medical News.

The controversy raises the question of whether many older adults are taking the thyroid hormone replacement drug levothyroxine when they don’t necessarily need to be, especially in the absence of symptoms.

As the senior population rapidly increases, it is important that physicians understand the nuances involved in recognizing and treating hypothyroidism in this age group. This article, the second in a Medscape Medical News series about thyroid disorders in older adults, explores these issues. The first article focused on management of hyperthyroidism in the senior population.

Peeling Back the Numbers

The reference intervals for thyroid function tests are determined by measuring the levels of free thyroxine 4 (T4) and thyrotropin, commonly called thyroid-stimulating hormone (TSH), in a population of healthy adults with no thyroid problems. The results in the middle 95% are considered normal, while those 2.5% above these levels and 2.5% below these levels are considered abnormal. In overt hypothyroidism, TSH levels are 2.5% above normal and free T4 levels are 2.5% lower than normal. In subacute/subclinical hypothyroidism, TSH levels are high, but free T4 levels are normal.

Subclinical hypothyroidism is defined by the US Preventive Services Task (USPSTF) as TSH level > 4.50 mIU/L with a normal free T4 level. The American and European thyroid associations classify subclinical hypothyroidism as either mild (TSH levels of 4-10 mlU/L) or severe (TSH levels > 10 mIU/L). Approximately 90% of patients with subclinical hypothyroidism have levels in the mild range, Xu said.

In older adults, TSH levels naturally rise, but the reason is unknown, Xu said. “It’s been reported in high-longevity patients in Italy, some in their 80s and 90s, as well as in other research,” he noted.

A recent study examined whether the one-size-fits-all approach to defining the reference ranges for thyroid function is too broad and should be modified to take into account age, sex, and race. The researchers included data from 8308 participants in the US National Health and Nutrition Examination Survey (NHANES) and 314,302 participants in a Chinese database. They found that the 97.5th percentile levels of TSH increased with age in the NHANES participants.

Using current reference intervals, the researchers found that the prevalence of subclinical hypothyroidism ranged from 2.4% for ages 20-29 years to 5.9% for ages ≥ 70 years. However, when they used reference intervals adjusted for age, sex, and race, 48.5% of those classified as having subclinical hypothyroidism no longer met the criteria — especially women and White participants.

When they applied the adjusted reference intervals to the Chinese database, they found that 73.5% of participants labeled with subclinical hypothyroidism and 60% of those originally labeled as having overt hypothyroidism were then reclassified as euthyroid.

Xu noted that most physicians don’t use adjusted TSH reference ranges to diagnose thyroid disease in older adults and that use of the current TSH normal range in this population often results in overtreatment.

Guidance from the French Endocrine Society proposes a “pragmatic solution” to establishing the TSH threshold for adults older than 60 years, Xu noted. It suggests that the upper limit of normal is the decade of the patient’s age divided by 10 (eg, TSH ≤ 7 IU/L for a 70-year-old patient).

A Look at Symptoms

Among the most common symptoms of hypothyroidism are dry skin, cold sensitivity, fatigue, muscle cramps, voice changes, constipation, depression, and weight gain, as well as irregular menstrual cycles and fertility problems in women of reproductive age.

The symptoms commonly attributed to thyroid dysfunction are poorly predictive of the presence of underlying thyroid dysfunction, Hennessey said. However, in people younger than 60 years, symptoms “carry more weight than in older people,” he added.

Older adults with subclinical hypothyroidism may not have any symptoms, and when they do, the symptoms are often mild and nonspecific, Xu said.

“Although fatigue is generally considered a hallmark symptom, not every patient with subclinical hypothyroidism experiences it, and thus, we might regard subclinical hypothyroidism as a primarily biochemical or laboratory diagnosis rather than a clinical diagnosis,” he said.

People with normal levels of thyroid hormones may have symptoms that overlap with hypothyroidism, Xu noted. He pointed to the Colorado Thyroid Disease Prevalence Study that involved state fair attendees who were aged 18 years or older. It found that 17% of euthyroid individuals reported four or more symptoms commonly associated with hypothyroidism, along with 20% of those with subclinical hypothyroidism and 25% of individuals with overt hypothyroidism.

Xu also pointed to the TRUST trial, a multicenter randomized, placebo-controlled parallel-group trial that investigated the impact of levothyroxine treatment on older patients with previously untreated subclinical hypothyroidism. It found that normalization of TSH levels with levothyroxine didn’t improve perceived mental and physical fatigue related to certain activities, as measured by the Pittsburgh Fatigability Scale.

To Treat or Not to Treat?

It is generally agreed that overt hypothyroidism (ie, TSH > 10 mIU/L and low free T4) should be treated. Untreated or undertreated hypothyroidism can result in cardiovascular disease, obesity, hypertension, poor physical capacity, and worse quality of life, as well as fertility problems in women of reproductive age. 

But controversy exists about whether to treat subclinical hypothyroidism — especially in older adults, Xu noted.

Hennessey believes that levothyroxine is often overprescribed. He cited research estimating that 30.5% or even 54% of individuals newly started on this T4 replacement drug in the US have normal thyroid function. A 2018 study found that levothyroxine treatment was not associated with improved thyroid-related symptoms or general quality of life in nonpregnant adults with subclinical hypothyroidism.

The question, according to Xu, is “whether there are benefits or whether there might be harm if we overtreat older patients with subclinical hypothyroidism who may not actually require treatment.”

Hennessey said there are potential harms, including unnecessary expenses for prescriptions, extra lab tests, and follow-up care, as well as iatrogenic thyrotoxicosis — especially in older women.

In deciding whether to initiate treatment in symptomatic patients, the first step is to determine the cause of the thyroid problem, Hennessey said.

Part of that process is making sure that the TSH results are consistent and accurate, Xu said. He characterized TSH as a “snapshot in time.”

When assessing a patient with elevated TSH, it’s important to ensure that thyroid function remains stable for at least a few weeks because several factors can affect TSH levels. These include time of day (TSH levels peak in early morning hours), season of year (levels may be higher in winter than in summer), stress, illness, medications, interindividual variation, age, sex (women tend to have higher TSH levels), and autoimmunity (eg, Hashimoto thyroiditis). A retest of TSH should be conducted 2-3 months after the first test, he advised.

In younger people, there may be cardiovascular benefits in treating patients with subclinical hypothyroidism, especially in the setting of cardiovascular risk factors, Xu said. “It may be reasonable to initiate treatment with low-dose levothyroxine and monitor the patient for 3-6 months. If the symptoms aren’t improving at six months, then repeat the labs and clinical evaluation,” he advised.

But most older patients with subclinical hypothyroidism don’t need to be treated, Xu said. He advises physicians treating patients who are 65 years or older to use the French Endocrine Society’s method of estimating the age-appropriate TSH level. If it is within the goal range, thyroid antibodies are negative, and the patient is asymptomatic, he recommends taking a “wait-and-see” approach.

A paper co-authored by Xu summarizes the guidance of major societies regarding management of mild subclinical hypothyroidism. It notes that all the major organizations and societies — the USPSTF, European Thyroid Association, American Association of Clinical Endocrinology and the American Thyroid Association, American Thyroid Association, American College of Physicians, and the American Academy of Family Physicians — recommend treatment in severe cases, but most don’t recommend immediate treatment in mild cases. Recommendations typically advise watchful waiting (unless the patient is symptomatic) and individualized treatment.

However, if the patient is symptomatic (even if TSH is within the age-appropriate goal range) or has risk factors (eg, a positive thyroid peroxidase antibody test, goiter, atherosclerotic cardiovascular disease, heart failure, or risk factors for these conditions) a trial of oral levothyroxine can be considered.

Hennessey noted that many patients who have elevated TSH (based on currently employed laboratory reference ranges) and are symptomatic may request to be treated with thyroid hormone.

“Even before coming into your office, they may have already seen their results on the patient portal, with an asterisk next to an ‘elevated’ TSH and concluded that they have hypothyroidism,” he said. “But if we adjust the TSH by age, race, gender, and decade, we can reclassify many of these patients as normal.”

Educating patients is very important so they understand that their symptoms are likely not due to hypothyroidism. “And then we can put in the hard work to look at other potential reasons for the patient’s symptoms and treat those appropriately,” Hennessey said. “Patients are likely to receive higher quality and more targeted care and are more likely to feel better because their treatment is focused on an actual problem, a correct diagnosis.”

Hennessey reported being involved in clinical drug development for AbbVie and Accela. Xu disclosed having no relevant financial relationships. 

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape Medical News and WebMD, and is the author of several consumer-oriented health books, as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).