The dynamic pituitary response to escalating-dose TRH stimulation test in hypothyroid patients treated with liothyronine or levothyroxine replacement therapy

Abstract

CONTEXT: 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. OBJECTIVE: We characterized the pituitary-thyroid axis in hypothyroid patients receiving equivalent doses of L-T3 or L-T4 by escalating-dose TRH stimulation test. DESIGN: A secondary analysis of a L-T3 vs L-T4 therapy trial was performed. SETTING: The study was conducted at the National Institutes of Health. PATIENTS: Thirteen patients were studied. INTERVENTIONS: Escalating-dose (5, 15, and 200 μg) TRH stimulation test on both treatment arms. MAIN OUTCOME MEASURES: 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. RESULTS: 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). CONCLUSIONS: 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.