Subclinical Hyperthyroidism: Considerations in Defining the Lower Limit of the Thyrotropin Reference Interval

BACKGROUND: Although numerous reports have discussed the upper limit of the thyrotropin (TSH) reference interval, none have dealt with the lower limit. Recent recommendations regarding subclinical thyroid dysfunction give different advice about its management, depending on whether the TSH concentration is <0.1 mIU/L or 0.1-0.4 mIU/L. CONTENT: We review key studies that have investigated the links between low TSH concentrations, cardiovascular morbidity, and mortality, with a focus on the TSH measurement threshold and assay type. SUMMARY: Despite numerous consensus guidelines and publications of expert opinion, the management of subclinical hyperthyroidism remains largely intuitive and non evidence-based. The primary reason for this unsatisfactory situation is the absence of clinical-intervention trials. Important aspects that remain to be addressed are the influence of the method used to measure TSH, the definition of normality, and the lack of evidence to base the grading of cardiovascular risk on the degree of TSH suppression. A risk-based approach should be adopted to determine the thresholds that would justify interventions. Such considerations assume, of course, that proof will emerge from ongoing clinical trials to support the medical utility of treating subclinical hyperthyroidism. (C) 2008 American Association for Clinical Chemistry