Spontaneous Subclinical Hypothyroidism in Patients Older than 55 Years: An Analysis of Natural Course and Risk Factors for the Development of Overt Thyroid Failure

Abstract

We aimed to analyze the natural course of subclinical hypothyroidism, quantify the incidence rate of overt hypothyroidism, and evaluate the risk factors for the development of definitive thyroid failure in elderly patients. One hundred seven patients (93 women and 14 men) over age 55 yr with subclinical hypothyroidism and no previous history of thyroid disease were prospectively studied. Subjects were followed up for 6-72 months (mean, 31.7 months) with repeated determinations of TSH and free T(4). Twenty-eight patients (26.8%) developed overt hypothyroidism, and 40 (37.4%) showed normalization of their TSH values. The incidence rate of overt hypothyroidism was 9.91 cases per 100 patient-years in the whole population, and 1.76, 19.67, and 73.47 cases per 100 patient-years in subjects with initial TSH values between 5.0-9.9, 10.0-14.9, and 15.0-19.9 mU/liter, respectively. Kaplan-Meier analysis showed that the development of definitive thyroid hypofunction was significantly related to the presence of symptoms of hypothyroidism, goiter, positive thyroid antibodies (P < 0.05), and mainly low normal free T(4) (P < 0.01) and high TSH (P < 0.0001) concentrations at baseline. A stepwise multivariate Cox regression analysis showed that the only significant factor for progression to overt hypothyroidism was serum TSH concentration (P < 0.0001). In conclusion, TSH concentration is the most powerful predictor for the outcome of spontaneous subclinical hypothyroidism in patients over age 55 yr. Subjects with mildly elevated TSH have a low incidence rate of overt hypothyroidism. We recommend follow-up with clinical and biochemical monitoring in these patients.

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

“…We necessitate further research to verify our findings and hypothesis Nearly half of our individuals with mild SCH (49.7%) experienced a normalization of thyroid function during a 3-year period in our study. The rate of spontaneous normalization in this study was similar to that reported in Japan (53.5% over 4.2 years), but was higher than rates reported in the USA (35% over 2 years) [6], Brazil (22.8% over 5 years) [7] and Spain (37.4% over 0.5-6 years) [10]. Huber et al [11] even reported a 4% rate of regression in a population that included patients with diagnosed thyroid diseases.…”

“…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].…”