CONTEXT: Mutations of the 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: To determine if the high T3 levels could also contribute to some critical features observed in these patients.

RESULTS: A 16 years old boy with severe psychomotor retardation and hypotonia, was hospitalized for malnutrition (body weight=25kg) and delayed puberty. He had tachycardia (104/min), high SHBG level (261nmol/L) and elevated serum FT3 level (11.3pmol/L), without FT4 and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of PTU, then PTU+LT4 was tested. After PTU (200mg/day), serum FT4 was undetectable, FT3 was reduced (3.1pmol/L) with high TSH levels (50.1mUl/L). Serum SHBG levels were reduced (72nmol/L). While PTU prescription was continued, high LT4 doses (100µg/day) were needed to normalize serum TSH levels (3.18mU/L). At this time serum FT4 was normal (16.4pmol/L), FT3 was slightly high (6.6pmol/L). Tachycardia was abated (84/min), weight gain was 3kg in one year and SHBG was 102nmol/L.

CONCLUSIONS: 1) When thyroid hormone production is reduced by PTU, high doses of LT4 (3.7µg/kg/day) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T3 levels might exhibit some deleterious effects on adipose, hepatic and cardiac levels. 3) PTU+LT4 could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation.