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.