SAT-615 A Novel Mutation and Presentation of Thyroid Hormone Resistance in a Neonate

Abstract

Abstract Background: Thyroid hormone resistance (THR) is a rare disorder that usually presents in later childhood to adulthood with elevations in total and free T4 and T3 and inappropriately normal to elevated thyroid stimulating hormone. Patients can have generalized or pituitary resistance to thyroid hormone and can present with ADHD, growth failure and even symptoms of hyperthyroidism. We present a premature neonate with a spontaneous novel mutation of the thyroid hormone receptor beta gene and her course to 3 years of life. Clinical Case: A 35-week female was transferred to the NICU for temperature instability, apnea and feeding difficulties. Newborn screen showed a thyroxine (T4) level of >34.1 ng/dL with concern for hyperthyroidism. Repeat testing showed a thyroid stimulating hormone (TSH) of 3.9 uUI/mL with T4 of 44.8 ng/dL and T3 of 330 ng/dL on day of life 8. Thyroid antibodies were negative. She had a normal brain MRI and thyroid ultrasound. At one week, she developed thrombocytopenia requiring transfusion. She had intermittent sinus tachycardia with mild pulmonary stenosis and a PFO on echocardiogram that was thought to be physiologic. At one month of life, testing revealed a novel spontaneous heterozygous mutation at c.1295delG of THRB gene. In the first year, she developed a milk protein intolerance and failure to thrive. She had gross motor delays and started therapy at 9 months requiring physical, occupational and feeding therapies. Halter monitoring showed intermittent sinus tachycardia that resolved after 6 months of life. She also had mild sleep difficulties early on. There were no other signs of clinical hyperthyroidism. Formal hearing and ophthalmologic testing was normal. Her platelets normalized after 1 month of life and testing for neonatal alloimmune thrombocytopenia was negative. She had oral feeding aversion without swallowing dysfunction and required a gastrostomy tube at age two. She developed obstructive sleep apnea requiring tonsillectomy and adenoidectomy at 2.5 years. Her height and weight remained below the 3rd percentile for the first 2 years of life. After her gastrostomy tube placement, she improved to the 10th percentile for height and weight which is at the bottom end of her genetic potential. She was discharged from PT at age 3. Thyroid function tests showed a marginally elevated TSH at 2 months with otherwise inappropriately normal TSH levels and elevated T4 and T3 levels. Recent thyroid testing at age 3 was TSH 4.04 uIU/mL (0.7-5.97), T3 465ng/dL (83-252) and freeT4 >7.77ng/dL (0.85-1.75). She has not been treated with any thyroid medication. Conclusion: Little is known about THR in the neonatal and early childhood period. This child had neonatal diagnosis with mild signs of hyperthyroidism, thrombocytopenia, feeding dysfunction and FTT early in life with a novel mutation of the THRB gene.