Low Thyrotropin From Nonthyroidal Illness? Response

To the Editor: I enjoyed reading “Thyroid Status and 6-Year Mortality in Elderly People Living in a Mildly Iodine-Deficient Area: The Aging in the Chianti Area Study” by Ceresini and colleagues. Subclinical hyperthyroidism was defined as a thyrotropin level of less than 0.46 mIU/L, free thyroxine (FT4) of 0.77 to 2.19 ng/dL, and free triiodothyronine (FT3) of 2.77 to 5.27 pg/mL. Low T3 syndrome, or nonthyroidal illness, was diagnosed when FT3 was less than 2.77 pg/mL with normal thyrotropin. After adjusting for multiple confounders, participants with subclinical hyperthyroidism (hazard ratio = 1.65) had significantly greater all-cause mortality than those with normal thyroid function. The discussion states that interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) measurements gave further support to the exclusion of nonthyroidal illness in the group with subclinical hyperthyroidism. The specific data regarding IL6 and TNF-α values in subclinical hyperthyroidism were not included.1 I must admit that I have not kept up on this field, although it is my understanding that nonthyroidal illness, medications (e.g., glucocorticoids), and hypothalamic-pituitary disease can also suppress thyrotropin levels.2 I would be surprised if these situations are always associated with low FT3 or FT4 levels during a single blood draw. It is difficult to label all the individuals with low thyrotropin and normal levels of thyroid hormone as having endogenous subclinical hyperthyroidism with overproduction of thyroid hormone without further testing or follow-up. A review states “Confronted with a low serum level of thyrotropin, physicians should not jump to the conclusion that it is due to a hyperthyroid state.”3 Perhaps some or many of the individuals with biochemically defined “subclinical hyperthyroidism” did not have endogenous thyroid disease and simply had a nonthyroidal illness that increased all-cause mortality and lowered thyrotropin levels. I would appreciate the authors' recommendations regarding assessment and follow-up of individuals with biochemical evidence of “subclinical hyperthyroidism” with a single blood draw. How can the practitioner determine the cause of the low thyrotropin value in an individual? Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that the author has no financial or any other kind of personal conflicts with this paper. Author Contributions: I am the sole author. Sponsor's Role: There was no sponsor.