Serum thyrotrophin at baseline predicts the natural course of subclinical hyperthyroidism

Objective Optimal therapeutic strategies for subclinical hyperthyroidism are undecided. Overt disease develops in a minority of cases, but the risk factors for progression remain unclear. We examined whether a baseline thyrotrophin (TSH) predicted progression to overt hyperthyroidism in asymptomatic individuals with subclinical hyperthyroidism. Design, patients and measurements This was a retrospective study of 323 patients with subclinical hyperthyroidism seen in our institution from 2003 to 2010 (mean age 71 years, males 26.9%, females 73.1%, mean follow-up duration 32 months, range 693 months). Serum TSH and free thyroxine (FT4) were documented at baseline and during follow-up. After excluding individuals with nonthyroid causes of low TSH, patients were grouped according to initial TSH as: TSH 0.100.39 mU/l (grade I) and TSH < 0.10 mU/l (grade II). Results Only 38 patients (11.8%) developed overt hyperthyroidism with annual progression rates of 0.63.7%. Most patients reverted to normal thyroid status (31.6%) or remained subclinically hyperthyroid (56.7%). Progression to frank hyperthyroidism was higher in grade II than in grade I patients (20.3% vs 6.8%, P < 0.001, Chi square test). KaplanMeier curves showed faster progression rates in grade II than grade I (P < 0.001, log rank test). In stepwise multivariate Cox regression analysis, TSH < 0.1 mU/l was associated with overt hyperthyroidism (hazard ratio 3.4, confidence interval 1.67.0), whereas age, gender, FT4 and aetiological diagnosis were not associated with hyperthyroidism. Conclusions Thyrotrophin predicts overt hyperthyroidism in asymptomatic individuals with subclinical hyperthyroidism. Patients with TSH < 0.10 mU/l have a higher risk of progressing to hyperthyroidism than those with TSH 0.100.39 mU/l.