Aim: Resistance to thyroid hormone (RTH) is a disease characterized by decreased sensitivity to thyroid hormone in the peripheral tissues such as cell membrane, metabolism, or nuclear receptor. In THRB gene mutation induced RTH, the effect of T3 on TRβ mutant receptors in the liver and the pituitary decreased, on TRα receptors located in the brain and heart increased. Triacs activity is similar to T3.
Case: A 1-month-old girl patient was admitted because of detection of elevated TSH level in the national screening program. With regards to her family history there was no thyroid disease in the family and in the mother of the patient during pregnancy. The patients physical examination revealed a live gaze, anterior fontanel 3×3 cm, body weight of 3500 g (1025 p), height 52 cm (2550 p), pulse: 190/min, blood pressure: 90/pulse, thyroid stage 0, and puberty tanner stage 1. In his laboratory, sT3: 8.62 pg/ml (2.764.38), sT4: 3.31ng/dl (0.751.49), TSH: 7.86 μIU/ml (0.775.64), thyroglobulin: 105 ng/dl (1.659.9), İodine(urine): 12.7 ug/dl, TSH receptor antibody (TRAB): 8.36 U/L (014), thyroid autoantibodies were negative. Her mother tested normal for thyroid functioning. In the genetic analysis of the patient suspected of thyroid hormone resistance, the P453H c.1358C>A mutation was detected heterozygously at the 10th exon of the THRB gene. Triac therapy began at 0.5 mg/kg/day (1750 mcg/day) In the follow up examination, the patients pulse rate decreased to normal and sT3: 6.09 pg/ml (2.764.38), sT4: 1.41 ng/dl (0.75-1.49),TSH: 7.44 μIU/ml (0.775.64).
Conclusion: In RTH due to THRB gene mutations, Triac binds to mutant TRβ receptors, reducing the effect of TRα receptors on the decrease in thyroid function tests and the decrease in fT3 levels. Like in our case, cases of high levels of fT3 have been reported in the literature when clinical recovery was obtained with Triac therapy. This effect is thought to be secondary to the cross-reaction. In view of this, or this reason, triac dose titration should take into account clinical improvement as well as thyroid function tests.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology