Background: There is little information regarding the natural history of subclinical hyperthyroidism (SH) due to Graves disease (GD). The objectives of this study were to assess the natural course of individuals with SH due to GD over a prolonged period. We also investigated the factors contributing to the progression or remission in these patients.
Methods: A prospective analysis of patients with SH due to GD between 2007 and 2013 who had at least 12 months of follow-up was performed. SH was diagnosed if serum TSH was below the laboratory reference range (0.4 4.0 mU/l) and when free thyroid hormones were normal. GD was confirmed by either a raised TSH receptor antibody level (TRAb) or uniform uptake on Technetium scan. Data regarding demographics, clinical and biochemical parameters were also collected.
Results: Forty-four patients (89% female, 16% current smokers and 5% with active Graves orbitopathy) were diagnosed with SH due to GD. Over the follow-up period (mean 30 months), approximately one third (34%) of the cohort progressed to overt hyperthyroidism, one third (34%) normalised their thyroid function, slightly less than one third (30%) remained in the SH state while one person became hypothyroid. Multivariate regression analysis showed that older age and positive anti-TPO antibody status had a positive association with risk of progression to overt hyperthyroidism with Hazard Ratios of 1.05 (95% CI 1.011.08, P<0.01) and 10.15 (1.8356.23, P<0.01), independent of other risk factors including current smoking, TRAb levels at diagnosis or gender.
Conclusions: A third each of patients with SH due to GD progress, normalise or remain in the SH state. Older people and those with positive anti-TPO antibodies have a higher risk of progression of the disease. This seminal data needs to be verified and confirmed in larger cohorts and over longer period of follow-up.