Treatment of subclinical hyperthyroidism in patients older than 50 years: A randomized controlled study

Abstract

Objective: Subclinical hyperthyroidism (SCH) is common and associated with atrial fibrillation (AF) risk in the elderly. Current guidelines rely on a low level of evidence.

Methods: Randomized clinical trial including patients 50 years and older, with TSH <0.4 mU/L and normal thyroid hormone concentrations. All patients showed autonomy on thyroid scan. They were randomized either to receive radioiodine (I131) or to be monitored and treated only if they underwent AF or evolved towards overt hyperthyroidism. Primary outcome was the onset of new AF. Secondary outcomes were treatment-induced hypothyroidism rate and health-related quality of life.

Results: 144 patients (mean age 65.3±8.9y, 76% female) were randomized, 74 to surveillance and 70 to treatment. Four patients in the surveillance group and one in the treatment group developed AF (p=0.238). However, the patient who developed AF in the treatment group maintained TSH <0.4 mU/L at AF onset. A post-hoc analysis was carried out and showed that when normalization of TSH was considered, the risk of AF was significantly reduced (p=0.0003). In the surveillance group, several patients showed no classical characteristics associated with AF risk, including age>65y or TSH<0.1mU/L. Of 94 patients treated using radioiodine, 25% developed hypothyroidism during follow-up.

Conclusions: Due to recruitment difficulties this study failed to demonstrate that SCH treatment can reduce significantly the incidence of AF in patients older than 50 years with thyroid autonomy even if all the patients who developed AF maintained TSH <0.4 mU/L. This result must be balanced with the increased risk of radioiodine-induced hypothyroidism.

Figure 1

Flow-chart of the study. ITT, Intention to treat; PP, per protocol.

Figure 2

The top panel shows Kaplan–Meier survival curve for freedom of atrial fibrillation depending on the treatment or surveillance group (P = 0.238). The bottom panel shows Kaplan–Meier survival curve for freedom of atrial fibrillation depending on TSH concentration at the end of the study (P = 0.0003).

Figure 3

Evolution of TSH, FT4 and FT3 during the study in both groups. The error bars are 95% confidence intervals. Top panels show intention to treat analysis; bottom panels show post-hoc analysis.