Many Thyroid Diagnoses May Be Wrong Without Race and Age Based Ranges

New research suggests current thyroid test standards may misclassify millions of patients

Topline

A large U.S. study found that nearly half of patients diagnosed with subclinical hypothyroidism may actually have normal thyroid function if test results are interpreted using age, sex, and race specific reference ranges for TSH and TT4. This reclassification could reduce unnecessary treatments and lead to more accurate thyroid care.

Study Details

Thyroid disorders are commonly diagnosed through blood tests that measure TSH (thyroid-stimulating hormone) and TT4 (total thyroxine). However, most labs use a universal “normal” range regardless of a person’s age, sex, or race an approach now being called into question.

Researchers led by Dr. Yongfeng Song from Central Hospital Affiliated to Shandong First Medical University in China used U.S. data from over 8,000 adults in the National Health and Nutrition Examination Survey (NHANES) to determine whether personalized reference intervals would change the way thyroid conditions are classified.

Methodology

Using five cycles of NHANES data, the study team calculated new TSH and TT4 “normal” ranges tailored to each participant’s age, sex, and race. These adjusted thresholds were then compared to current standard reference intervals to assess how patient classifications would change.

The standard reference intervals were:

• TSH: 0.45–4.5 mIU/L

• TT4: 4.5–13.2 μg/dL

Conditions were classified as:

• Overt hypothyroidism: High TSH + Low TT4

• Subclinical hypothyroidism: TSH high, TT4 normal

• Overt hyperthyroidism: Low TSH + High TT4

• Subclinical hyperthyroidism: TSH low, TT4 normal

Key Findings

The use of age-, sex-, and race-specific reference intervals led to substantial reclassification:

• 48.5% of those previously diagnosed with subclinical hypothyroidism were reclassified as normal

• 31.2% with subclinical hyperthyroidism were also reclassified as normal

• Most of these changes occurred in women, white patients (hypothyroidism), and Black or Hispanic patients (hyperthyroidism)

• A small number of cases shifted between overt and subclinical categories or were reclassified as normal

This suggests that the “normal” TSH and TT4 levels can differ significantly across demographics and that current standards may be too rigid or outdated.

Implications for Practice

For Patients:

If you’ve been told you have a mild thyroid problem especially if your symptoms are vague or absent it might be worth asking whether your lab results were interpreted using personalized ranges. Unnecessary thyroid treatment can lead to side effects like fatigue, heart issues, and even bone loss.

For Providers:

This study highlights a need to reconsider blanket TSH/TT4 thresholds. Applying age, sex, and race specific reference intervals may reduce overdiagnosis, prevent overtreatment, and better target those truly in need of therapy. Lab software and clinical guidelines may need to evolve to support this shift.

An editorial in Annals of Internal Medicine emphasized that up to 30% of U.S. patients started on L-thyroxine may not actually need it and more precise diagnostic criteria could help change that.