학술논문
Long-Term Efficacy of T3 Analogue Triac in Children and Adults With MCT8 Deficiency: A Real-Life Retrospective Cohort Study
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Geest, Ferdy S. van; Groeneweg, Stefan; Akker, Erica L.T. van den; Bacos, Iuliu; Barca, Diana; Berg, Sjoerd A.A. van den; Bertini, Enrico; Brunner, Doris; Brunetti-Pierri, Nicola; Cappa, Marco; Cappuccio, Gerarda; Chatterjee, Krishna; Chesover, Alexander D.; Christian, Peter; Coutant, Regis; Craiu, Dana; Crock, Patricia; Dewey, Cheyenne; Dica, Alice; Dimitri, Paul; Dubey, Rachana; Enderli, Anina; Fairchild, Jan; Galuchan, Jonathan; Garibaldi, Luigi R.; George, Belinda; Hackenberg, Annette; Heinrich, Bianka; Huynh, Tony; Ktosowska, Anna; Lawson-Yuen, Amy; Linder-Lucht, Michaela; Lyons, Greta; Lora, Felipe Monti; Moran, Carla; Miiller, Katalin E.; Paone, Laura; Paul, Praveen G.; Polak, Michel; Porta, Francesco; Reinauer, Christina; Rijke, Yolanda B. de; Seckold, Rowen; Menevse, Tuba Seven; Simm, Peter; Simon, Anna; Spada, Marco; Stoupa, Athanasia; Szeifert, Lilla; Tonduti, Davide; Toor, Hans van; Turan, Serap; Vanderniet, Joel; Waart, Monique de; Wal, Ronald van der; Walt, Adri van der; Wermeskerken, Anne-Marie van; Wierzba, Jolanta; Zibordi, Federica; Zung, Amnon; Peeters, Robin P.; Visser, W. Edward
Source
Journal of Clinical Endocrinology & Metabolism. March 2022, Vol. 107 Issue 3, pe1136, 12 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Thyroid hormone action is crucial for metabolic and developmental processes. Intracellular bioavailability of thyroid hormone is governed by plasma membrane transporters (1). Monocarboxylate transporter 8 (MCT8) is a specific thyroid [...]
Context: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. Objective: Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. Methods: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. Results: From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P< 0.0001; target 1.4-2.5 nmol/L). Body-weightfor-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P= 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P= 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) [micro]mol/L (mean increase 7 [micro]mol/L; 95% CI, 6-9; P< 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. Conclusions: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential ofTriac for MCT8 deficiency. Key Words: MCT8 deficiency, Allan-Herndon-Dudley syndrome, AHDS, T3 analogue, thyromimetic drug
Context: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. Objective: Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. Methods: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. Results: From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P< 0.0001; target 1.4-2.5 nmol/L). Body-weightfor-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P= 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P= 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) [micro]mol/L (mean increase 7 [micro]mol/L; 95% CI, 6-9; P< 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. Conclusions: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential ofTriac for MCT8 deficiency. Key Words: MCT8 deficiency, Allan-Herndon-Dudley syndrome, AHDS, T3 analogue, thyromimetic drug