Long-Term Efficacy of T3 Analogue Triac in Children and Adults With MCT8 Deficiency: A Real-Life Retrospective Cohort Study.
Journal: The Journal of clinical endocrinology and metabolism
Volume: 107
Issue: 3
Year of Publication: 2022
Affiliated Institutions:
Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, GD Rotterdam, The Netherlands.
Division of Endocrinology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, University Medical Center, GD Rotterdam, The Netherlands.
Centrul Medical Dr. Bacos Cosma, Timisoara , Romania.
Carol Davila University of Medicine, Department of Clinical Neurosciences, Paediatric Neurology Discipline II, Bucharest , Romania.
Diagnostic Laboratory for Endocrinology, Department of Internal Medicine, Erasmus Medical Center , GD Rotterdam, The Netherlands.
Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesu' Children's Research Hospital IRCCS, Rome, Italy.
Gottfried Preyer's Children Hospital, Vienna, Austria.
Department of Translational Medicine, Federico II University, Naples, Italy.
Division of Endocrinology, Bambino Gesu' Children's Research Hospital IRCCS, Rome, Italy.
Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB QQ, UK.
Division of Endocrinology, The Hospital for Sick Children and Department of Paediatrics, University of Toronto, Toronto, MG X, Canada.
East Kent Hospitals University NHS Foundation Trust, Ashford TN LZ, UK.
Department of Pediatric Endocrinology and Diabetology, University Hospital, Angers, France.
John Hunter Children's Hospital, New Lambton Heights, NSW , Australia.
Genomics Institute Mary Bridge Children's Hospital, MultiCare Health System Tacoma, WA , USA.
Sheffield Children's NHS Foundation Trust, Sheffield Hallam University and University of Sheffield, Sheffield, S TH, UK.
Medanta Superspeciality Hospital, Indore , India.
Department of Neuropediatrics, University Children's Hospital Zurich, Steinwiesstrasse , Zürich, Switzerland.
Department of Diabetes and Endocrinology, Women's and Children's Hospital, North Adelaide SouthAustralia.
Plymouth Hospitals NHS Trust, Plymouth, PL DH,UK.
UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA , USA.
Department of Endocrinology, St. John's Medical College Hospital, Bengaluru , India.
Department of Endocrinology & Diabetes, Queensland Children's Hospital, South Brisbane Queensland , Australia.
Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, - Gdańsk, Poland.
Division of Neuropediatrics and Muscular Disorders, Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.
Pediatric Endocrinology Group, Santa Catarina Hospital, São Paulo, -, Brazil.
Heim Pal National Institute of Pediatrics, Budapest, , Hungary.
Department of Paediatrics, Christian Medical College, Vellore , India.
Paediatric Endocrinology, Diabetology and Gynaecology Department, Necker Children's University Hospital, Imagine Institute, Université de Paris, Paris , France.
Department of Paediatrics, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino ,Italy.
Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Duesseldorf , Germany.
Department of Clinical chemistry, Erasmus Medical Center, GD Rotterdam, The Netherlands.
Marmara University School of Medicine Department of Pediatric Endocrinology, Istanbul , Turkey.
Royal Children's Hospital/University of Melbourne, Parkville ,Australia.
st Department of Pediatrics, Semmelweis University, Budapest, , Hungary.
Child Neurology Unit - C.O.A.L.A. (Center for Diagnosis and Treatment of Leukodystrophies), V. Buzzi Children's Hospital, Milano , Italy.
Private Paediatric Neurology Practice of Dr A van der Walt, Durbanville, South Africa.
Department of Paediatrics, Flevoziekenhuis, RA, Almere, The Netherlands.
Department of Internal and Pediatric Nursing, Institute of Nursing and Midwifery, Medical University of Gdańsk, - Gdańsk, Poland.
Child Neurology Unit, Fondazione IRCCS, Istituto Neurologico Carlo Besta, Milan , Italy.
Pediatric Endocrinology Unit, Kaplan Medical Center, University of Jerusalem, Rehovot , Israel.
Abstract summary
Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction.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.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.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-weight-for-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) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported.Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency.
Authors & Co-authors:
van Geest Ferdy S FS
Groeneweg Stefan S
van den Akker Erica L T ELT
Bacos Iuliu I
Barca Diana D
van den Berg Sjoerd A A SAA
Bertini Enrico E
Brunner Doris D
Brunetti-Pierri Nicola N
Cappa Marco M
Cappuccio Gerarda G
Chatterjee Krishna K
Chesover Alexander D AD
Christian Peter P
Coutant Régis R
Craiu Dana D
Crock Patricia P
Dewey Cheyenne C
Dica Alice A
Dimitri Paul P
Dubey Rachana R
Enderli Anina A
Fairchild Jan J
Gallichan Jonathan J
Garibaldi Luigi R LR
George Belinda B
Hackenberg Annette A
Heinrich Bianka B
Huynh Tony T
Kłosowska Anna A
Lawson-Yuen Amy A
Linder-Lucht Michaela M
Lyons Greta G
Monti Lora Felipe F
Moran Carla C
Müller Katalin E KE
Paone Laura L
Paul Praveen G PG
Polak Michel M
Porta Francesco F
Reinauer Christina C
de Rijke Yolanda B YB
Seckold Rowen R
Menevşe Tuba Seven TS
Simm Peter P
Simon Anna A
Spada Marco M
Stoupa Athanasia A
Szeifert Lilla L
Tonduti Davide D
van Toor Hans H
Turan Serap S
Vanderniet Joel J
de Waart Monique M
van der Wal Ronald R
van der Walt Adri A
van Wermeskerken Anne-Marie AM
Wierzba Jolanta J
Zibordi Federica F
Zung Amnon A
Peeters Robin P RP
Visser W Edward WE
Study Outcome
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