PuSH - Publication Server of Helmholtz Zentrum München

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)
Publ. Version/Full Text DOI
Free by publisher
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.
Additional Metrics?
Edit extra informations Login
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