Thyrotropin levels in a population with no clinical, autoantibody, or ultrasonographic evidence of thyroid disease: Implications for the diagnosis of subclinical hypothyroidism

Context: The current debate regarding whether to decrease the upper limit for the TSH reference range to 2.5 mu IU/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 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 with the Gaussian and lognormal distributions. Setting: This study was performed in the general community. Participants: Of 1861 Hanford Thyroid Disease Study participants with TSH measured by ELISA who also had thyroid peroxidase antibody measurements, 766 comprised the normal reference group 3 (NRG-3) with no evidence of thyroid disease, including no positive antibodies and normal thyroid ultrasound. Main Outcome Measure: TSH was measured. Results: The TSH distribution in the NRG (NRG-3) was right skewed and followed an approximate lognormal distribution. The best estimates of the 97.5th percentile, the percentage above 2.5 mu IU/ml, and the percentage above 3.0 mu IU/ml for TSH by 3rd generation immunochemiluminometric assay are 4.1 mu IU/ml, 20% and 10.2%, respectively. Conclusion: These results indicate that the TSH reference range should be narrowed and support a value of approximately 4.0 as the upper-reference limit.