Thyrotropin Levels in a Population with No Clinical, Autoantibody, or Ultrasonographic Evidence of Thyroid Disease: Implications for the Diagnosis of Subclinical Hypothyroidism

Abstract

The current debate regarding whether to decrease the upper limit for the TSH reference range to 2.5 microIU/ml has considerable potential impact on the diagnosis and treatment of subclinical hypothyroidism worldwide. We report an analysis of TSH distribution in a population with no evidence of thyroid disease, including a normal thyroid ultrasound. 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. This study was performed in the general community. 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. TSH was measured. 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 microIU/ml, and the percentage above 3.0 microIU/ml for TSH by 3rd generation immunochemiluminometric assay are 4.1 microIU/ml, 20% and 10.2%, respectively. These results indicate that the TSH reference range should be narrowed and support a value of approximately 4.0 as the upper-reference limit.