BACKGROUND
Thyroid function tests are commonly ordered to evaluate patients for possible thyroid problems. In particular, hypothyroidism is often screened for due to common nonspecific symptoms such as fatigue and weight gain. Thyroid-stimulating hormone (TSH) levels are the most common thyroid test ordered, followed by free thyroxine (FT4) measurements of the TSH is abnormal. If TSH levels are high and FT4 levels are low, it indicates overt hypothyroidism, which is usually treated with lifelong thyroid hormone therapy using levothyroxine. If FT4 levels are normal but TSH levels are high, it is called subclinical hypothyroidism. There is ongoing debate about whether subclinical hypothyroidism should be treated.

Currently, laboratories use the same normal range for TSH and FT4 for all adults, regardless of age. However, some research suggests that TSH and FT4 levels may change with age. In particular, TSH levels appear to increase in older patients, so a TSH level that seems abnormal in a young adult might be normal for an older adult. This could lead to some people being treated unnecessarily, even when their test results are appropriate for their age.

The goal of this study was to establish age-specific normal reference ranges for TSH and FT4.

THE FULL ARTICLE TITLE
Jansen HI et al. Age-specific reference intervals for thyroid- stimulating hormones and free thyroxine to optimize diagnosis of thyroid disease. Thyroid. Epub 2024 Sep 30

SUMMARY OF THE STUDY
The authors analyzed lab data from 13 medical institutions in the Netherlands, collected from patients between 2008 and 2022. This data included over 7.6 million TSH measurements and 2.2 million FT4 measurements.

They calculated age-specific normal ranges for TSH and FT4 levels using advanced statistical methods.

They discovered that TSH levels are naturally higher in children compared to adults. In adults, TSH levels tend to increase with age, especially after 50 in women and 60 in men. For example, the upper normal limit for TSH in 50-year-old women was 4.0 mIU/L, but by age 90, it increased by 50% to 6.0 mIU/L. In contrast, Free T4 levels stayed relatively stable throughout adulthood.

The study also found that using these age-specific normal ranges could significantly reduce the number of people diagnosed with subclinical hypothyroidism. Among women aged 50-60, the rate of subclinical hypothyroidism would drop from 13.1% to 8.6%. In women aged 90-100, it would decline from 22.7% to 8.1%. Similar decreases were seen in men, with the diagnosis of subclinical hypothyroidism falling from 10.9% to 7.7% in men aged 60-70 and from 27.4% to 9.6% in those aged 90-100.

The impact on overt hypothyroidism was smaller but still noticeable. Among women aged 50-60, the diagnosis rate would decrease from 3.0% to 2.2%, while in men, it would drop from 1.7% to 1.4%.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The results of this study show that it is normal for levels of TSH increase with age in adults, starting at age 50 for women and age 60 for men. Using age-specific reference ranges for normal thyroid function can help avoid overdiagnosing and over-treating both subclinical and overt hypothyroidism.

— Phillip Segal, MD FRCPC

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