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Wirth, E.K.* ; Sheu, S.Y.* ; Chiu-Ugalde, J.* ; Sapin, R.* ; Klein, M.O.* ; Mossbrugger, I. ; Quintanilla-Martinez, L. ; Hrabě de Angelis, M. ; Krude, H.* ; Riebel, T.* ; Rothe, K.* ; Köhrle, J.* ; Schmid, K.W.* ; Schweizer, U.* ; Grüters, A.*

Monocarboxylate transporter 8 deficiency: Altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy.

Eur. J. Endocrinol. 165, 555-561 (2011)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Context Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland. Objective To characterise the potential impact of MCT8-deficiency on thyroid morphology in a patient and in Mct8-deficient mice. Design Thyroid morphology in a patient carrying the A224V mutation was followed by ultrasound imaging for over 10 years. After thyroidectomy, a histopathological analysis was carried out. The findings were compared with histological analyses of mouse thyroids from the Mct8(-/y) model. Results We show that an inactivating mutation in MCT8 leads to a unique, progressive thyroid follicular pathology in a patient. After thyroidectomy, histological analysis revealed gross morphological changes, including several hyperplastic nodules, microfollicular areas with stromal fibrosis and a small focus of microfollicular structures with nuclear features reminiscent of papillary thyroid carcinoma (PTC). These findings are supported by an Mct8-null mouse model in which we found massive papillary hyperplasia in 6- to 12-month-old mice and nuclear features consistent with PTC in almost 2-year-old animals. After complete thyroidectomy and substitution with levothyroxine (l-T(4)), the preoperative, inadequately low T(4) and free T(4) remained, while increasing the l-T(4) dosage led to T(3) serum concentrations above the normal range. Conclusions Our results implicate peripheral deiodination in the peculiar hormonal constellation of MCT8-deficient patients. Other MCT8-deficient patients should be closely monitored for potential thyroid abnormalities.
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Publication type Article: Journal article
Document type Scientific Article
Keywords no keywords
ISSN (print) / ISBN 0804-4643
e-ISSN 1479-683X
Quellenangaben Volume: 165, Issue: 4, Pages: 555-561 Article Number: , Supplement: ,
Publisher BioScientifica
Reviewing status Peer reviewed