{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:53:09Z","timestamp":1790401989255,"version":"4.1.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Mutations of the thyroid hormone (TH)-specific cell membrane transporter,\n                      <jats:italic toggle=\"yes\">monocarboxylate transporter 8<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">MCT8<\/jats:italic>\n                      ), produce an X-chromosome-linked syndrome of TH deficiency in the brain and excess in peripheral tissues. The clinical consequences include brain hypothyroidism causing severe psychoneuromotor abnormalities (no speech, truncal hypotonia, and spastic quadriplegia) and hypermetabolism (poor weight gain, tachycardia, and increased metabolism, associated with high serum levels of the active TH, T3). Treatment in infancy and childhood with TH analogues that reduce serum triiodothyronine (T3) corrects hypermetabolism, but has no effect on the psychoneuromotor deficits. Studies of brain from a 30-week-old MCT8-deficient embryo indicated that brain abnormalities were already present during fetal life.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A carrier woman with an affected male child (MCT8 A252fs268*), pregnant with a second affected male embryo, elected to carry the pregnancy to term. We treated the fetus with weekly 500\u2009\u03bcg intra-amniotic instillation of levothyroxine (LT4) from 18 weeks of gestation until birth at 35 weeks. Thyroxine (T4), T3, and thyrotropin (TSH) were measured in the amniotic fluid and maternal serum. Treatment after birth was continued with LT4 and propylthiouracil. Follow-up included brain magnetic resonance imaging (MRI) and neurodevelopmental evaluation, both compared with the untreated brother.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>During intrauterine life, T4 and T3 in the amniotic fluid were maintained above threefold to twofold the baseline and TSH was suppressed by 80%, while maternal serum levels remained unchanged. At birth, the infant serum T4 was 14.5\u2009\u03bcg\/dL and TSH &lt;0.01\u2009mU\/L compared with the average in untreated MCT8-deficient infants of 5.1\u2009\u03bcg\/ and &gt;8\u2009mU\/L, respectively. MRI at six months of age showed near-normal brain myelination compared with much reduced in the untreated brother. Neurodevelopmental assessment showed developmental quotients in receptive language and problem-solving, and gross motor and fine motor function ranged from 12 to 25 at 31 months in the treated boy and from 1 to 7 at 58 months in the untreated brother.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This is the first demonstration that prenatal treatment improved the neuromotor and neurocognitive function in MCT8 deficiency. Earlier treatment with TH analogues that concentrate in the fetus when given to the mother may further rescue the phenotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2020.0306","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T04:21:30Z","timestamp":1596514890000},"page":"713-720","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":29,"title":["Prenatal Treatment of Thyroid Hormone Cell Membrane Transport Defect Caused by\n                    <i>MCT8<\/i>\n                    Gene Mutation"],"prefix":"10.1177","volume":"31","author":[{"given":"Samuel","family":"Refetoff","sequence":"first","affiliation":[{"name":"Department of Medicine, The University of Chicago, Chicago, Illinois, USA."},{"name":"Department of Pediatrics, The University of Chicago, Chicago, Illinois, USA."},{"name":"Committees on Genetics, and The University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Pappa","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism and Nutrition, The University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith K.","family":"Williams","sequence":"additional","affiliation":[{"name":"Northwest Perinatal Center, Portland, Oregon, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Gisele","family":"Matheus","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Medicine, The University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Hansen","sequence":"additional","affiliation":[{"name":"Northwest Perinatal Center, Portland, Oregon, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Nicol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\u2013Endocrinology and Oregon Health &amp; Science University, Portland, Oregon, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\u2013Endocrinology and Oregon Health &amp; Science University, Portland, Oregon, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Blasco","sequence":"additional","affiliation":[{"name":"Neurodevelopmental Disabilities Doernbacher Children's Hospital, Oregon Health &amp; Science University, Portland, Oregon, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandie","family":"Wiebers Jensen","sequence":"additional","affiliation":[{"name":"Neurodevelopmental Disabilities Doernbacher Children's Hospital, Oregon Health &amp; Science University, Portland, Oregon, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Bernal","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid and Center for Biomedical Research on Rare Diseases, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy E.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Department of Medicine, The University of Chicago, Chicago, Illinois, USA."},{"name":"Department of Molecular Metabolism and Nutrition, The University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"LaFranchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\u2013Endocrinology and Oregon Health &amp; 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