Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure

J Clin Endocrinol Metab. 2004 Oct;89(10):4890-7. doi: 10.1210/jc.2003-032061.


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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Hypothyroidism / mortality*
  • Hypothyroidism / physiopathology*
  • Incidence
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Risk Factors
  • Survival Rate
  • Thyroid Gland / physiopathology*
  • Thyrotropin / blood


  • Thyrotropin