ESPE Abstracts

Resistance to thyroid hormone (RTH) is attributed to mutations in the thyroid receptor beta (RTH-β) gene. The syndrome is characterized by decreased sensitivity of target tissues to thyroid hormone (TH) action, leading to elevated TH levels, accompanied by normal or high thyroid-stimulating hormone (TSH) values, with variable clinical manifestations such as goiter, which is the most common finding, reported in 66–95% of cases and delayed growth and bone maturation, learning disabilities, hyperactivity, and tachycardia. Most of the affected children have attenuation in growth rate, leading in some cases to short stature as adults. Intriguingly, in this unique case, growth velocity was increased unexpectedly without a sign of precocious puberty or an increase in bone age. Our patient, who is today a 11.5 years old boy, was born at 37 weeks of gestation with a weight of 2050 grams. He was referred at the age of 2 years for growth assessment due to failure to thrive and short stature. Other than that, the child was a-symptomatic presenting without tachycardia and no goiter, had a normal echography and his cardiological assessment was normal. Over time, signs of hyperactivity developed as well as reduced attention span. TSH was in the upper normal range and his thyroid hormone values were 2-3 folds higher than the upper limit. Between the ages of 2-5 years, the child was growing below the 3rd percentile. He underwent a growth hormone stimulation test that was normal. His bone age was 2 years younger than his chronological age and this gap still exists today. Thus, in the absence of overt clinical signs of hyperthyroidism, we decided not to treat him with antithyroid drugs. Genomic DNA was extracted from peripheral blood leukocytes using the Flexi-Gene DNA Extraction Kit (Qiagen, Germany), and the p.Leu328SerExon 9 THRB gene de novo mutations were identified. In the 9 years of follow-up, his growth velocity was increased unexpectedly, growing now in the 15th percentile without signs of precocious puberty or an increase in bone age. We propose that this is due to compensation by an adaptive increase of TH activity over time.