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 6-93 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 0·10-0·39 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 0·6-3·7%. 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). Kaplan-Meier 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 1·6-7·0), 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 0·10-0·39 mU/l.