Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

John E M Midgley; Rolf Larisch; Johannes W Dietrich; Rudolf Hoermann

doi:10.1530/ec-150056

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

Endocr Connect. 2015 Dec;4(4):196-205. doi: 10.1530/ec-150056.

Authors

John E M Midgley¹, Rolf Larisch¹, Johannes W Dietrich², Rudolf Hoermann³

Affiliations

¹ North Lakes Clinical20 Wheatley Avenue, Ilkley LS29 8PT, UKDepartment of Nuclear MedicineKlinikum Luedenscheid, Paulmannshoeher Strasse 14, D-58515 Luedenscheid, GermanyMedical Department IEndocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, GermanyRuhr Center for Rare Diseases (CeSER)Ruhr University of Bochum and Witten/Herdecke University, Alexandrinenstraße 5, D-44791 Bochum, Germany.
² North Lakes Clinical20 Wheatley Avenue, Ilkley LS29 8PT, UKDepartment of Nuclear MedicineKlinikum Luedenscheid, Paulmannshoeher Strasse 14, D-58515 Luedenscheid, GermanyMedical Department IEndocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, GermanyRuhr Center for Rare Diseases (CeSER)Ruhr University of Bochum and Witten/Herdecke University, Alexandrinenstraße 5, D-44791 Bochum, Germany North Lakes Clinical20 Wheatley Avenue, Ilkley LS29 8PT, UKDepartment of Nuclear MedicineKlinikum Luedenscheid, Paulmannshoeher Strasse 14, D-58515 Luedenscheid, GermanyMedical Department IEndocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, GermanyRuhr Center for Rare Diseases (CeSER)Ruhr University of Bochum and Witten/Herdecke University, Alexandrinenstraße 5, D-44791 Bochum, Germany.
³ North Lakes Clinical20 Wheatley Avenue, Ilkley LS29 8PT, UKDepartment of Nuclear MedicineKlinikum Luedenscheid, Paulmannshoeher Strasse 14, D-58515 Luedenscheid, GermanyMedical Department IEndocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, GermanyRuhr Center for Rare Diseases (CeSER)Ruhr University of Bochum and Witten/Herdecke University, Alexandrinenstraße 5, D-44791 Bochum, Germany rudolf.hoermann@gmail.com.

Abstract

Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease. Peripheral deiodinase activity was calculated as a measure of T4-T3 conversion efficiency. In euthyroid subjects, the median l-T4 dose was 1.3 μg/kg per day (interquartile range (IQR) 0.94,1.60). The dose was independently associated with gender, age, aetiology and deiodinase activity (all P<0.001). Comparable FT3 levels required higher l-T4 doses in the carcinoma group (n=143), even after adjusting for different TSH levels. Euthyroid athyreotic thyroid carcinoma patients (n=50) received 1.57 μg/kg per day l-T4 (IQR 1.40, 1.69), compared to 1.19 μg/kg per day (0.85,1.47) in autoimmune thyroiditis (P<0.01, n=76) and 1.08 μg/kg per day (0.82, 1.44) in patients operated on for benign disease (P< 0.01, n=80). Stratifying patients by deiodinase activity categories of <23, 23-29 and >29 nmol/s revealed an increasing FT3-FT4 dissociation; the poorest converters showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001). An l-T4-related FT3-TSH disjoint was also apparent; some patients with fully suppressed TSH failed to raise FT3 above the median level. These findings imply that thyroid hormone conversion efficiency is an important modulator of the biochemical response to l-T4; FT3 measurement may be an additional treatment target; and l-T4 dose escalation may have limited success to raise FT3 appropriately in some cases.

Keywords: TSH; conversion; deiodinase; l-T4 therapy; levothyroxine; thyroid hormone replacement; triiodothyronine.