Role of Thyrotropin-Releasing Hormone Stimulation Test and Autoantibody in 952 Subjects with Subclinical Hypothyroidism

Context: Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) levels and normal free thyroxine (fT4) levels. In upper normal TSH levels, thyrotropin-releasing hormone (TRH) stimulation test proved to be useful in identifying an exaggerated TSH response.

Objective: We aimed to evaluate the incidence and predictive ability of basal TSH, anti-thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin antibodies (TgAb) for exaggerated TRH stimulation test in SCH.

Methods: A total of 952 subjects with SCH (TSH 4.01-10.00 mIU/L) found during health checkups were evaluated for TSH response to TRH stimulation testing and autoantibodies. Exaggerated TSH response was defined as ΔTSH (peak serum TSH level after TRH injection minus basal TSH level) of > 25.00 mIU/L.

Results: The prevalence of exaggerated TSH responses in SCH was 66% (n = 633). The proportion of exaggerated TSH response tended to increase as basal TSH levels increased (P for trend <.001). Also, the proportion of positive TPOAb or TgAb tended to increase as basal TSH levels increased (P for trend <.05). Analysis of predictive ability of basal TSH, positive TPOAb, or TgAb for exaggerated TRH stimulation test revealed that positive TPOAb or TgAb showed high specificity (> 90%) for positive TRH stimulation test but low sensitivity. Basal TSH showed low sensitivity and specificity.

Conclusion: Two-thirds of SCH showed exaggerated TRH stimulation test. Positive TPOAb or TgAb showed high specificity (> 90%) for positive TRH stimulation test but basal serum TSH levels showed low predictability. The TRH stimulation test may be a valuable guide to identify SCH patients with hypothyroid state.