Beneficial Effects of Propylthiouracil plusl-Thyroxine Treatment in a Patient with a Mutation inMCT8

Abstract

1) When thyroid hormone production was reduced by PTU, high doses of LT(4) (3.7 microg/kg.d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T(3) levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT(4) could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation.

Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities

“…Aiming to evaluate the influence of serum T3 on the body mass index Wémeau and cols. studied the effects of treatment with propylthiouracil (PTU) (200 mg/day) in an undernourished 16 year-old boy with a loss of function mutation of MCT8 (15). After a period of treatment with PTU levothyroxine was added to the treatment at doses of 50, 75, and 100 mg/day (15).…”

“…studied the effects of treatment with propylthiouracil (PTU) (200 mg/day) in an undernourished 16 year-old boy with a loss of function mutation of MCT8 (15). After a period of treatment with PTU levothyroxine was added to the treatment at doses of 50, 75, and 100 mg/day (15). While treatment with PTU alone reduced free T4, normalized free T3, and increased TSH serum levels, the introduction of levothyroxine, especially in the 100 mg/day dose, allowed TSH and free T4 levels return to those levels obtained before the introduction of PTU (15).…”

“…After a period of treatment with PTU levothyroxine was added to the treatment at doses of 50, 75, and 100 mg/day (15). While treatment with PTU alone reduced free T4, normalized free T3, and increased TSH serum levels, the introduction of levothyroxine, especially in the 100 mg/day dose, allowed TSH and free T4 levels return to those levels obtained before the introduction of PTU (15). More importantly, this strategy improved body mass index as a consequence of the increase in the rate of weight gain from 200 g/year to 3 kg/year (this treatment had no effect on cerebral disturbances and the psychomotor retardation) (15).…”

Syndromes of Reduced Sensitivity to Thyroid Hormone

“…A prominent and common feature in MCT8 deficient patients is the failure to thrive, which may require in some cases a gastric feeding tube. Possible reasons for low weight and muscle wasting are difficulty swallowing on neurological basis, and increased metabolism due to the thyrotoxic state of peripheral tissues caused by the high serum T 3 levels [82,[85][86][87].…”

“…Therefore, high L-T 4 dose treatment has been used in combination with propylthiouracil (PTU), which is a specific inhibitor of D1. Benefit was limited to reduction of the hypermetabolism and weight loss, without improvement of the neuropsychomotor deficit [87] The use of thyromimetic drugs that do not require MCT8 to enter tissues are currently under investigation. One such TH analogue, DITPA, is effectively transported into mouse brain in the absence of Mct8 [107].…”