Risk for Progression to Overt Hypothyroidism in an Elderly Japanese Population with Subclinical Hypothyroidism

Abstract

Background: Few population-based studies report the changes with time in thyroid function tests in patients with subclinical hypothyroidism. We compared the risk for developing overt hypothyroidism in patients with subclinical hypothyroidism and euthyroid controls from the same population of elderly Japanese. We also sought associations of selected parameters with the development of overt hypothyroidism in the subclinical hypothyroid and euthyroid groups. Methods: We measured thyrotropin (TSH) and free thyroxine (T4) levels at baseline examinations performed from 2000 to 2003 in the cohort of Japanese atomic-bomb survivors and identified 71 patients with spontaneous subclinical hypothyroidism (normal free T4 and TSH > 4.5 mIU/L without a history of thyroid treatment, mean age 70 year) and 562 euthyroid controls. We re-examined TSH and free T4 levels an average of 4.2 years later (range, 1.9-6.9). Results: The risk for progression to overt hypothyroidism was significantly increased in subclinical hypothyroid patients (7.0%) compared with control subjects (1.6%) after adjusting for age and sex (odds ratio, 4.56; p = 0.009). Higher baseline TSH levels were associated with progression from subclinical to overt hypothyroidism ( p = 0.02) in the multivariate analysis, including age, sex, antithyroid peroxidase antibody, and ultrasonography (US) findings. The analysis using binary TSH data suggested that a TSH level > 8 mIU/L was a predictive value for development of overt hypothyroidism ( p = 0.005). On the other hand, serum TSH levels spontaneously normalized in 38 (53.5%) of the patients with subclinical hypothyroidism. In the multivariate analysis, normalization of TSH levels was associated with lower baseline TSH levels ( p = 0.004) and normal and homogenous thyroid US findings ( p = 0.04). Atomic-bomb radiation dose was not associated with subclinical hypothyroidism or its course. Conclusions: Subclinical hypothyroidism was four times more likely to be associated with development of overt hypothyroidism than euthyroid controls in the sample population of Japanese elderly. TSH levels in half of the patients normalized spontaneously when assessed after an average follow-up period of 4.2 years. Baseline TSH level and thyroid US findings are potential predictors of future thyroid function in subclinical hypothyroidism.

Natural history of mild subclinical hypothyroidism in a middle-aged and elderly Chinese population: a prospective study

“…An investigation conducted in Japan [8] drew a similar conclusion, but risks were higher either in SCH subjects (7.0%) or euthyroid subjects (1.6%) than in our study. The difference might partly result from the higher baseline TSH levels in their study population, as they enrolled some severe SCH patients.…”

“…Although these results are less comparable because of different characteristics of participants in the different studies, we found a regression rate higher than most previous studies in our study, which was the only one to enroll only patients with mild SCH from both sexes. Based on previous studies and expert reviews, we used 7.0 mIU/L of TSH as cut-off points [1,13] and found that higher TSH concentrations significantly impaired the likelihood of TSH normalization in our logistic regression analysis, similar to previous studies [6,8,10]. Accordingly, the generally lower TSH levels among our cases compared with previous studies may be one of the reasons that TSH normalization occurred in a high proportion of our patients.…”

“…Furthermore, in addition to TSH and TPOAb status, lipid profiles and renal function may influence the course of the disease in some ways. A total of 505 mild SCH patients completed the present study, more than several previous studies on this topic [6][7][8][9][10][11]. Compared with other studies, we included individuals aged 40-years or older instead of only elderly people in both sexes [6][7][8][9][10][11].…”

“…The predictive value of TSH levels, TPOAb status and ultrasound for the natural history of the disease have been investigated [6][7][8][9][10][11][12]. However, important metabolic indices such as TC or creatinine (CR) have not been researched.…”

“…On the other hand, the proportion of patients with spontaneous normalization of thyroid function is 20%-53.5%. Age, sex, initial TSH levels and thyroid peroxidase antibodies (TPOAb) status may influence thyroid function [4,[6][7][8][9][10][11][12]. However, when referring to the natural history of "mild" SCH, only Rosário et al have focused on this topic in only the female population, and found the prognostic value of ultrasound [7,9].…”