August 15, 2006: Carole Spencer Ph.D., FACB
The development of the sensitive 3rd. generation TSH immunometric assay (functional sensitivity 0.01 mIU/L) has revolutionized thyroid testing. In fact, it is now well established that TSH measurement is more diagnostically sensitive than free T4 (FT4) for assessing ambulatory patients with normal hypothalamic-pituitary function and stable thyroid status. This is because the log-linear relationship between TSH and FT4 dictates that TSH will be the first abnormality to appear in early developing hypo- or hyperthyroidism. Because subclinical thyroid disease is a biochemical diagnosis based on the detection of a TSH abnormality without a FT4 abnormality, the accuracy of the setting of the TSH reference range becomes critical. Unfortunately, because TSH measurement has a low “index of individuality” the TSH population reference range is an insensitive parameter to use for detecting thyroid dysfunction in individual patients. Furthermore, it is now clear that the upper TSH population reference limit (97.5 percentile) is skewed from ~2.5 to ~ 4.0 mIU/L by the inclusion of individuals with occult thyroid dysfunction who do not have detectable thyroid autoantibodies (TPOAb or TgAb). The current debate concerning the setting of the TSH upper reference limit* relates to the question of whether mild TSH elevations have any clinical consequences. The large body of literature concerning the diagnosis and efficacy of treating mild subclinical hypothyroidism has primarily focused on crude biological parameters such as clinical symptoms and cholesterol. More recent studies are suggesting that mild subclinical hypothyroidism may indeed be a risk factor for atherosclerosis in susceptible patients, through a variety of mechanisms associated with atherogenesis. This presentation proposes that the diagnosis and efficacy of treating subclinical hypothyroidism should not be based on the TSH reference range alone but should integrate the degree of TSH elevation with patient-specific risk factors and the concentration of TPO antibodies.
*Wartofsky et al JCEM 90:5483, 2005 and Surks JCEM 90:5489, 2005