Context: The current debate regarding whether to decrease the upper limit for the thyrotropin (TSH) reference range to 2.5 µiU/ml has considerable potential impact on the diagnosis and treatment of subclinical hypothyroidism worldwide.

Objective: We report an analysis of TSH distribution in a population with no evidence of thyroid disease, including a normal thyroid ultrasound.

Design: A subset of the Hanford Thyroid Disease Study (HTDS) cohort was used to examine the TSH distribution in a population having no evidence of thyroid disease, seronegative thyroid autoantibodies, no history of thyroid medications, and a normal thyroid ultrasound. The shape of the TSH distribution was compared to the Gaussian and log normal distributions.

Setting: General community.

Participants: Of 1861 HTDS participants with TSH measured by ELISA who also had thyroid peroxidase antibody measurements, 766 comprised the Normal Reference Group with no evidence of thyroid disease, including no positive antibodies and normal thyroid ultrasound.

Main Outcome Measure: TSH.

Results: The TSH distribution in the Normal Reference Group (NRG-3) was right skewed and followed an approximately log normal distribution. The best estimates of the 97.5^th percentile, the percent above 2.5 µiU/ml, and the percent above 3.0 µiU/ml for TSH by 3^rd generation ICMA are 4.1 µiU/ml, 20% and 10.2%, respectively.

Conclusions: These results indicate that the TSH reference range should be narrowed and support a value of approximately 4.0 as the upper reference limit.