The Dynamic Pituitary Response to Escalating-Dose TRH Stimulation Test in Hypothyroid Patients Treated With Liothyronine or Levothyroxine Replacement Therapy

Abstract

A recent trial showed that 1:3 μg:μg liothyronine (L-T3) substitution for levothyroxine (L-T4) achieving near-identical TSH levels resulted in a significant decrease in weight and cholesterol levels with no appreciable changes in cardiovascular parameters, suggesting a differential peripheral response to the therapy. We characterized the pituitary-thyroid axis in hypothyroid patients receiving equivalent doses of L-T3 or L-T4 by escalating-dose TRH stimulation test. A secondary analysis of a L-T3 vs L-T4 therapy trial was performed. The study was conducted at the National Institutes of Health. Thirteen patients were studied. Escalating-dose (5, 15, and 200 μg) TRH stimulation test on both treatment arms. Study outcomes were peak serum TSH concentration (Cmax), time to peak TSH concentration (Tmax), area under the curve from 0 to 60 minutes (AUC₀₋₆₀) after TRH injection. Thirteen patients aged 51.2 ± 8.29 years completed escalating-dose TRH stimulation test. No significant difference between L-T3 and L-T4 treatments was observed in TSH Cmax or area under the curve. L-T4 resulted in a small but significantly shorter Tmax compared to L-T3 (3.5 ± 0.73 min on 200 μg TRH dose, P < .03). In addition, 5 μg TRH dose compared to 200 μg resulted in a shorter Tmax on both treatment arms (6.9 ± 0.59 min L-T3, 4 ± 0.3 min L-T4; P = .0002). The assessment of the dynamic pituitary response to escalating doses of TRH confirms that substitution of L-T3 for L-T4 on a 1:3 ratio achieves a near-identical degree of pituitary euthyroidism. Furthermore, the data suggest that lower doses of TRH might provide clinically relevant information of thyrotroph function, particularly when investigating partial pituitary insufficiency states.