Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient with a mutation in MCT8.

TLDR: When thyroid hormone production was reduced by PTU, high doses of LT(4) (3.7 microg/kg) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone.

Abstract: Context: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T3 levels. Lack of MCT8 transport of T3 in neurons could explain the neurological phenotype. Objective: Our objective was to determine whether the high T3 levels 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 FT4 and 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) was tested. After PTU (200 mg/d), serum FT4 was undetectable, FT3 was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/li...