Natural Course of Euthyroidism and Clues for Early Diagnosis of Thyroid Dysfunction: Tehran Thyroid Study.

Abstract

Considering the limited data available on the natural course of euthyroidism, this study was designed to evaluate the progression in time from euthyroidism to subclinical or overt hypo- or hyperthyroidism. This study was conducted within the framework of the Tehran Thyroid Cohort Study, in which 5783 individuals aged 40.4 ± 0.2 years were followed for six years. The overall loss to follow-up rate was 8.3%. After applying exclusion criteria, data of 4204 euthyroid subjects remained for analysis of a six-year natural course analysis. Thyroid function tests, clinical characteristics, and metabolic characteristics were assessed at baseline and every three years. The annual incidence rates [confidence intervals (CI)] of subclinical and overt hypothyroidism were 7.62 [CI 7.39-7.85) and 2.0 [CI 1.94-2.06] per 1000 persons, respectively. For thyroid hyperfunction, the annual incidence rates of subclinical and overt hyperthyroidism were 0.92 [0.90-0.95) and 0.68 [0.66-0.70) per 1000 persons, respectively. Euthyroid persistency was 93.24% during 6 years. Predictive factors for conversion to thyroid dysfunction were thyrotropin, free thyroxine and thyroid peroxidase antibody levels, sex, and smoking. Criteria for early diagnosis of hypothyroidism (i.e., sensitivity of 94% and specificity of 82%, p < 0.0001) were obtained based on baseline and three-year follow-ups of thyroid function tests and thyroid peroxidase antibody. Early diagnosis of hypothyroidism was significantly associated with impaired glucose tolerance (relative risk with 3.03 [CI 1.36-6.75]; p = 0.007), high cholesterol (relative risk 2.46 [CI 1.45-4.18]; p = 0.001), obesity (relative risk 2.92 [CI 1.64-5.2]; p < 0.001), and hypertension (relative risk 1.68 [CI 1.53-1.84]; p < 0.04). This study shows that after a six-year follow-up in an iodine sufficient area, 6.7% of euthyroid subjects were found to progress to thyroid dysfunction, in particular subclinical hypothyroidism.