Beneficial Effects of Propylthiouracil plus l-Thyroxine Treatment in a Patient with a Mutation in MCT8

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/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU prescription was continued, high LT₄ doses (100 μg/d) were needed to normalize serum TSH levels (3.18 mU/liter). At that time, serum FT₄ was normal (16.4 pmol/liter), and FT₃ was 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 T₃ levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT₄ could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation.