Context: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T3levels. Lack of MCT8 transport of T3in neurons could explain the neurological phenotype. Objective: Our objective was to determine whether the high T3levels could also contribute to some critical features observed in these patients. Results: A 16-yr-old boy with severe psychomotor retardation and hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter), and elevated serum free T3(FT3) level (11.3 pmol/liter), without FT4and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU) and then PTU plus levothyroxine (LT4) wastested. After PTU (200 mg/d), serum FT4was undetectable, FT3was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU prescription was continued, high LT4doses (100 μg/d) were needed to normalize serum TSH levels (3.18 mU/liter). At that time, serum FT4was normal (16.4 pmol/liter), and FT3was slightly high (6.6 pmol/liter). Tachycardia was abated (84 beats/min), weight gain was 3 kg in 1 yr, and SHBG was 102 nmol/liter. Conclusions: 1) When thyroid hormone production was reduced by PTU, high doses of LT4(3.7 μg/kg·d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T3levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT4could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation. Copyright,
Journal of Clinical Endocrinology and Metabolism
Erasmus MC: University Medical Center Rotterdam

Wémeau, J. L., Pigeyre, M., Proust-Lemoine, E., D'Herbomez, M., Gottrand, F., Jansen, J., … Ladsous, M. (2008). Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient with a mutation in MCT8. Journal of Clinical Endocrinology and Metabolism, 93(6), 2084–2088. doi:10.1210/jc.2007-2719