Thyrotoxicosis in MCT8 deficiency
Monocarboxylate transporter 8 (MCT8) deficiency, also known as Allan-Herndon-Dudley syndrome, is a rare, severely debilitating, and life-limiting genetic disorder caused by variants in the SLC16A2 gene that render the MCT8 thyroid hormone transporter partially or completely dysfunctional. MCT8 is highly expressed throughout the body, including the brain. Its deficiency disrupts thyroid hormone homeostasis and is associated with 2 distinct concomitant clinical presentations: persistent peripheral thyrotoxicosis resulting from elevated serum levels of triiodothyronine and neurodevelopmental impairment arising from low thyroid hormone levels in the brain. The disorder severely impacts quality of life and reduces life expectancy to a median of 35 years due to a range of clinical sequelae, with approximately 30% of affected individuals dying during childhood. Recognition and treatment of thyrotoxicosis are crucial to prevent associated symptoms and long-term sequelae.
Authors
- A. R. Cappola
- Athanasia Stoupa (ORCID: https://orcid.org/0000-0002-1164-5862)
- Bauer Aj
- Lindsey Nicol (ORCID: https://orcid.org/0000-0002-4073-6683)
- K Chatterjee
- Luca Persani (ORCID: https://orcid.org/0000-0003-2068-9581)
- Salman Razvi (ORCID: https://orcid.org/0000-0002-9047-1556)
- Kristien Boelaert
- Johannes W Dietrich
Institutions
- Délégation Paris 5 (FR)
- Children's Hospital of Philadelphia (US)
- Oregon Health & Science University (US)
- University of Milan (IT)
- Université Paris Cité (FR)
- University of Cambridge (GB)
- University Hospitals of the Ruhr-University of Bochum (DE)
- Newborn Screening Ontario (CA)
- Assistance Publique – Hôpitaux de Paris (FR)
- St. Elisabeth-Hospital Bochum (DE)
- Wellcome/MRC Institute of Metabolic Science (GB)
- IRCCS Istituto Auxologico Italiano (IT)
- Klinik Blankenstein (DE)
- St. Josef-Hospital (DE)
- University of Pennsylvania (US)
- University of Birmingham (GB)
- Newcastle University (GB)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- The Journal of Clinical Endocrinology & Metabolism
- Published
- 2026-01-08
- DOI
- https://doi.org/10.1210/clinem/dgaf707
- Primary Topic
- Thyroid Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- Sanofi
- Hexal AG
- Ultragenyx Pharmaceutical
- Argenx
- National Institute for Health and Care Research
- British Thyroid Foundation
- Singapore Institute for Clinical Sciences
- Ministero della Salute
- Eisai
- Novo Nordisk
- Alexander S. Onassis Public Benefit Foundation
- Ipsen
- Medical Research Council
- Science and Engineering Research Board