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Inherited defects of thyroid hormone-cell-membrane transport: review of recent findings

Fu, Jiaoa; Refetoff, Samuelb; Dumitrescu, Alexandra M.a

Current Opinion in Endocrinology, Diabetes and Obesity: October 2013 - Volume 20 - Issue 5 - p 434–440
doi: 10.1097/
THYROID: Edited by Lewis E. Braverman and Angela M. Leung

Purpose of review This review summarizes the most significant findings over the last year regarding human and animal models deficient in thyroid hormone cell-membrane transporters (THCMTs). Although several THCMTs have been modelled in genetically engineered mice, the only THCMT defect known in humans is that caused by mutations in the monocarboxylate transporter 8 (MCT8) gene.

Recent findings The importance of several amino acid residues has been assessed in vitro to further our understanding on the structure–function of the MCT8. The administration of the thyromimetic compound, diiodothyropropionic acid, has been tested in patients with MCT8 gene mutations, following studies of its use in mice. Another thyroid hormone analogue, 3,3′,5,5′-tetraiodothyroacetic acid, was tested in Mct8-deficient mice. The phenotypes of L-type aminoacid transporter 2 and organic anion transporting polypeptide 1C1 deficiencies have been studied in mouse models. Mct8/organic anion transporting polypeptide 1C1 double knockout mice have been shown to manifest neurodevelopmental deficits. Zebrafish is emerging as another vertebrate model that may be useful to study the role of Mct8 in brain development.

Summary Studies on the pathogenesis and therapy of MCT8 deficiency are in progress, and new vertebrate models that are suitable to study the neurological consequences of the syndrome are being explored.

aDepartment of Medicine, The University of Chicago

bDepartments of Medicine, Pediatrics and Genetics, The University of Chicago, Chicago, Illinois, USA

Correspondence to Alexandra M. Dumitrescu, MD, PhD, Department of Medicine, The University of Chicago, 5841 S. Maryland Avenue MC3090, Chicago, IL 60637, USA. Tel: +1 773 702 6577; fax: +1 773 702 6940; e-mail:

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins