Normal TSH Reference Range in Adults
The normal reference range for serum thyroid-stimulating hormone (TSH) in adults is 0.4–4.5 mIU/L, though this upper limit shifts upward with advancing age, particularly after age 50–60 years.
Standard Adult Reference Range
The widely accepted TSH reference range for adults is 0.4–4.5 mIU/L, based on the 2.5th to 97.5th percentile distribution in disease-free populations, as established by NHANES III data and endorsed by the American Association of Clinical Endocrinologists 1, 2.
The geometric mean TSH in healthy adults is approximately 1.4 mIU/L, which represents the central tendency of normal thyroid function 1.
The lower threshold of 0.4 mIU/L remains relatively stable across all adult age groups, while the upper limit increases progressively with age 1.
Age-Related Adjustments to the Upper Limit
After age 40–50 years, the upper limit of the TSH reference range begins to rise, reaching approximately 5.0 mIU/L by age 90 3, 4.
In individuals aged ≥80 years, approximately 12% have TSH levels >4.5 mIU/L without any underlying thyroid disease, indicating that the standard population reference interval may be inappropriate for older adults 1.
Age-specific upper limits have been proposed: approximately 3.75 mIU/L at age 40, increasing to 5.0–7.5 mIU/L by age 80–90 1, 3, 5.
Despite these age-related shifts, using age-specific reference ranges reclassifies only 0.1–1.9% of middle-aged adults as normal versus abnormal compared to a fixed cutoff of 4.0 mIU/L; however, in those aged ≥85 years, reclassification rates are higher at 2.1–4.7% 3.
Gender Differences
Women tend to have slightly higher median TSH values than men (approximately 1.6 mIU/L vs 1.4 mIU/L), and the 97.5th percentile is also higher in females 6.
However, these gender differences are relatively small and not considered clinically significant enough to require separate reference ranges in routine practice 7.
Laboratory and Assay Considerations
TSH reference intervals vary between different manufacturer assays and laboratory platforms, so each laboratory should ideally establish its own reference range using the specific immunoassay employed 7.
At TSH concentrations around 4.0 mIU/L, inter-method differences between assays can be approximately 1 mIU/L, which may affect clinical decision-making as much as age-related variation 3.
The TSH assay used should have a functional sensitivity of at least 0.02 mIU/L to accurately detect suppressed levels 2.
Important Caveats Affecting TSH Interpretation
Day-to-day TSH variability can reach 50% of mean values, and serial measurements taken at the same time of day can vary by up to 40%, making a single TSH measurement insufficient for diagnosis 1, 7.
Acute illness, hospitalization, certain medications (dopamine, glucocorticoids, iodine, octreotide, bexarotene), pregnancy (especially first trimester), adrenal insufficiency, and pituitary disorders can all transiently suppress or alter TSH levels independent of true thyroid dysfunction 1, 2, 7.
Recovery from severe illness or destructive thyroiditis can cause transient TSH elevation that normalizes spontaneously 2.
Heterophilic antibodies against mouse proteins can cause falsely elevated TSH in some assays 2.
Clinical Application Algorithm
For screening asymptomatic adults <80 years: Use the standard reference range of 0.4–4.5 mIU/L 1, 2.
For adults aged 80+ years: Consider an upper limit of 5.0–7.5 mIU/L to avoid overdiagnosis, recognizing that TSH naturally rises with age 1, 3, 5.
Always confirm abnormal TSH values with repeat testing after 3–6 weeks, as 30–60% of mildly abnormal results normalize spontaneously 1, 8.
Measure free T4 alongside TSH when TSH is abnormal to distinguish subclinical from overt thyroid dysfunction 1, 2.
Stricter Reference Ranges in Specific Populations
When intensive screening excludes individuals with anti-TPO antibodies (a marker of autoimmune thyroid disease), the upper TSH limit decreases to approximately 3.4–3.7 mIU/L 9.
However, the U.S. Preventive Services Task Force found inadequate evidence that screening for or treating thyroid dysfunction in asymptomatic adults improves quality of life, cardiovascular outcomes, or mortality, so routine screening using stricter cutoffs is not recommended 1.
Common Pitfalls to Avoid
Do not diagnose thyroid dysfunction based on a single TSH measurement, as physiological variation is substantial 1, 7.
Do not apply adult reference ranges to children, as pediatric TSH values are physiologically higher, particularly in neonates and young children 7.
Do not ignore clinical context: TSH interpretation must account for acute illness, medications, pregnancy, and other factors that transiently affect TSH secretion 1, 2, 7.
Do not assume all laboratories use identical reference ranges; verify the specific range for your laboratory's assay platform 7, 3.