ESPE Abstracts

Introduction: Thyroid hormone resistance (THR) is a syndrome characterized by decreased response to thyroid hormones in target tissues. Thyroid hormone receptor resistance alpha (THRRα) is an autosomal dominant inherited disease that is characterized by near-normal thyroid function tests (TFT) and tissue-specific hypothyroidism, and is likely to be missed in practice.

Case: 10-month-old male patient was referred to us because of abnormality in TFT. It was learned from his history that he had been treated for constipation and anemia for a long time, and that his neurological development stages were lagging behind. On physical examination, he had a coarse facial appearance, flattened nasal root, and broad anterior fontanelle. TSH: 3.9 mI/IU (0.7-8.4), fT4: 0.89 ng/dl (0.9-2.2), fT3: 5.3 pg/ml (2.8-4.4), TG: 65.9 ng/ml (12-113), urinary iodine was 12.5 μg/dL. Thyroid USG was normal. The patient was diagnosed with central hypothyroidism and L-thyroxine treatment was started. Speech delay and motor coordination disorder were added to the findings in the follow-up, despite regular drug intake and normal fT4 levels, and he was diagnosed with specific learning disability by the child psychiatrist. Gross and fine motor coordination disorder partially regressed with LT4 treatment and special training. However, in the follow-ups, the patient's growth velocity was at the lower limit. His height was 3-10p, IGF-1 level was low, and his bone age was 1.5-2 years delay. When the chronological age was 11, growth hormone (GH) was started in the patient whose growth rate fell below 5 cm/year and there was no response to GH stimulation tests. Re-evaluation was requested from genetics with the findings of 'short stature, resistant anemia, hypothyroidism, learning disability, epiphyseal dysplasia'. Autosomal dominant inherited heterozygous c.1193C>G (P.PRO398Arg) variant in the THRA gene was detected in the patient. Since this result was consistent with clinical findings, patient was diagnosed with THRRα.

Conclusion: Because of the genetic and phenotypic heterogeneity of THRRα syndromes, the diagnosis and optimal treatment are unclear. While our patient was being followed up with central hypothyroidism, dysmorphic findings and prominent growth retardation made us suspect THR syndromes. In such cases, whole exome sequencing and diagnostic biomarkers may facilitate the diagnosis. L-thyroxine therapy may improve some metabolic abnormalities, constipation, and dyspraxia, especially in those with mild mutations or those diagnosed early. There are also patients receiving GH in the literature. Our case is being followed up with a combination of LT4 and GH treatment.