Etiology and clinical natural progress of subclinical thyroid diseases

Etiology and Clinical Natural Progress of Subclinical Thyroid Diseases Introduction: A group of patients with abnormal serum TSH levels, normal free T3 and normal free T4 levels was defined after radioimmunoassay methodology was developed for TSH measurements in 1960's. This condition, with abnormal serum TSH levels, normal free T3 and normal free T4 levels is called subclinical thyroid disease. Our research was designed to reveal clinical characteristics and natural history of subclinical thyroid diseases. Material and Methods: 31 subclinical hypothyroidism and 73 subclinical hyperthyroidism patients who admitted to our endocrinology outpatient clinic, from December 2013 to July 2014, were investigated. Patients were followed-up for a maximum 6 months or until specific therapy was started. Therapy was not started unless there was a certain indication; pregnancy with subclinical hypothyroidism, atrial fibrilation with subclinical hyperthyroidism, etc. Data from our research was defined as percentage; mean, median, minimum and maximum values. IBM SPSS Statistics 20.0 software was used for statistical analysis. Basal TSH and lipid profile levels were analysed with Mann-Whitney U test, paired-samples t-test and Wilcoxon test. Findings: 104 subclinical thyroid disease patients were enrolled in the study. 73 patients (70.2%) had subclinical hyperthyroidism, 31 patients (29.8%) had subclinical hypothyroidism. 16.3% of total patients were anti-tiroglobulin antibody positive, 31.7% of total patients were anti-TPO antibody positive. In the subclinical hyperthyroidism group anti-tiroglobulin and anti-TPO prevalances were 11% and 23% respectively. In the subclinical hyperthyroidism group, mean basal TSH level was 0,18 mIU/L (95% CI 0,162-0,2088 mIU/L; min: 0.01 mIU/L, max: 0.33 mIU/L); TSH levels did not fit Gaussian distribution and median level was 0.22 mIU/L. Mean basal free T3 level was 3.13 pg/ml (95% CI 3.02-3.23pg/ml; min: 2.28 pg/ml, max: 4.23 pg/ml); mean basal free T4 level was 0.87 ng/dl (95% CI 0.8487-0.9036 ng/dl; min: 0.5 ng/dl, max: 1.12 ng/dl). 49.3% of subclinical hyperthyroidism group became spontaneously euthyroid during 6 months follow-up period. In the same group, the difference between median basal TSH level of the patients who did became euthyroid spontaneously was significantly higher than the median basal TSH level of the patients who did not became euthyroid (Mann-Whitney U test p value: 0.026) The difference between mean and median of repeated lipid profile measurements, during disease and after spontaneous recovery, was not statistically significant. Subclinical hyperthyroidism etiology was autonomously functioning soliter nodüle or multiple nodüles in 24 patients (32.9%); Graves disease in 12 patients (16.4%); subacute thyroiditis in 7 patients (9.6%) and Hashitoxicosis in 3 patients (4.1%). In the subclinical hypothyroidism group, mean basal TSH level was 6,85 mIU/L (95% CI 6.4331-7.2598 mIU/L; min: 5.5 mIU/L, max: 9.23 mIU/L); TSH levels did not fit Gaussian distribution and median level was 6.7 mIU/L. Mean basal free T3 level was 2.98 pg/ml (95% CI 2.8315 – 3.1433 pg/ml; min: 1.97 pg/ml, max: 3.8 pg/ml); mean basal free T4 level was 0.79 ng/dl (95% CI 0.747-0.8317 ng/dl; min: 0.61 ng/dl, max: 1.13 ng/dl). In this group anti-TPO antibody was found positive in 51.6% and anti- 12 tiroglobulin antibody was found positive in 29%. 51.6% of subclinical hypothyroidism group became spontaneously euthyroid during 6 months follow-up period. In the same group, the difference between median basal TSH levels of the patients who did became euthyroid spontaneously and of the patients who did not, was not statistically significant. Also in the subclinical hypothyroidism group, like subclinical hyperthyroidism group, the difference between mean and median of repeated lipid profile measurements, during disease and after spontaneous recovery, was not statistically significant. Subclinical hypothyroidism etiology was Hashimoto disease in 16 patients (51.6%). Discussion And Conclusions: Subclinical hypothyroidism and subclinical hyperthyroidism patients show similar symptoms with overt thyroid disease. The clinician must evaluate benefits of treatment and natural history of subclinical thyroid disease to decide on the treatment. The high rates of spontaneous recovery shows that these patients should not be treated unless there is a certain indication (cardiac comorbidities, pregnancy with subclinical hypothyroidism, etc). Short term subclinical thyroid function impairment does not result in certain metabolic problems as clinical thyroid disease does. Etiology and symptoms of patients, with persistent subclinical thyroid disease, must be evaluated to decide on treatment. Keywords: Subclinical thyroid disease, hypothyroidism, hyperthyroidism, anti-TPO, TSH