A novel mutation in the thyroid hormone receptor β gene in a patient who developed thyroid nodules.

OSCAR BRUNETTO; EZEQUIELA ADROVER; LORENA HIDALGO CORONADO; MÓNICA BRE; MOLINA, MARICEL F.; ALFREDO CHAMOUX; MARCELO LAHAN; RIVOLTA, CARINA M.

Florianópolis

Congreso; XXVIII Congreso Latinoamericano de Endocrinología Pediátrica.; 2019

Sociedad Latinoamericana de Endocrinología Pediátrica.

Background: Thyroid hormone Resistance (THR) is a genetic disorder characterized by decreased tissue sensitivity to thyroid hormones (THs). The key finding is the presence of high concentrations of THs in the presence of non-suppressed TSH. Clinical phenotype is highly variable since signs of hormone deficiency, sufficiency and excess could coexist. High TSH produces goiter, being the most common feature. It has been associated with increased risk of developing thyroid nodules, with malignancy risk. Management of nodules associated with THR is as other nodules, with fine-needle aspiration guided by ultrasound (US) as first approach and ATA recommendation of surgery in children when Bethesda category is III or higher.Clinical case: A 11-year-old girl with diagnosis of triple X syndrome was referred because of goiter and abnormal thyroid function test with TSH 3.01 mIU/ml; fT4 2.5 ng/ml and T3 286 ng/dl. Antithyroid antibodies and TRAb were negative. She had no signs or symptoms of hyperthyroidism except for tachycardia. She received propranolol and methimazole for a short time which later was dropped because of suspicion of THR. In order to identify mutations causing THR, genomic DNA was isolated from blood cells. Exons 7-10 of THRβ gene, including the flanking intronic regions were direct sequenced. A novel missense mutation in exon 9: c.917A>C transvertion that results in a p.K306T substitution was revealed. The substitution is located in a position evolutionarily conserved and modifies the electrostatic surface of the THRβ. The mutation was not found in her parents. Two years later, a thyroid US revealed mixed nodules, mainly cystic in both lobes, the biggest of 20x10mm. FNA was performed and reported as Bethesda IV, so she underwent thyroidectomy. Histology was reported as nodular hyperplasia. Currently, she is euthyroid, on treatment with levothyroxine at high dosis.Conclusion: Clinical expression of THR is variable and should be suspected in front of discordant biochemical patterns. Genetic analysis is important to confirm the diagnosis of THR. We identified a novel and de novo mutation in exon 9 of THRβ gene. Our patient showed as well as others reported cases, goiter but with multiple nodules. Goiter should be monitored by US in order to detect nodules that require evaluation, until further studies can demonstrate if there is any risk factor for developing nodules or malignancy in THR patients. As our knowledge, there are no such studies to date.