Several studies have evaluated the natural course of overt hypothyroidism and risk factors for its development. In one previous United States study of elderly subjects (≥65 years old) [2], subclinical hypothyroidism remained in 56% of patients at a 2-year follow-up, while 35% showed euthyroidism and 2% overt hypothyroidism. In that study, higher TSH level and thyroid peroxidase (TPO) antibody (Ab) positivity were independently associated with persistent subclinical hypothyroidism, and a TSH level of 10 mU/L or higher was an independent risk factor for overt hypothyroidism. In another study, 36.4% of patients showed persistent subclinical hypothyroidism, 37.4% euthyroidism and 26.2% overt hypothyroidism after 6 to 72 months of follow-up (mean 31.7 months) [3]. TSH level was the only significant predictor of progression to overt hypothyroidism.

Recently, Lee et al. [4] reported that the initial TSH level was the only definite prognostic factor for persistent subclinical hypothyroidism. Also, TPO Ab titer was a helpful prognostic factor for maintenance of subclinical hypothyroidism in patients with mildly elevated TSH levels (5 to 10 mU/L). This result is consistent with those reported previously. However, the authors needed to perform a multivariate Cox regression analysis to identify prognostic or risk factors for persistent subclinical hypothyroidism. Simple comparison of baseline characteristics seems insufficient to conclude that TSH is a risk factor. In addition, it might be helpful to perform a survival analysis according to TSH range using Kaplan-Meier curves.

Determining the natural course and long-term clinical effects of subclinical hypothyroidism and identifying risk factors for persistent subclinical hypothyroidism would have implications for the follow-up and treatment of patients with subclinical hypothyroidism. Therefore, a long-term prospective study is needed.