ESPE Abstracts

A was born at 38+4 weeks by eutocic delivery, with adequate auxological parameters and unremarkable perinatal history. She was admitted to our center at 15 days of life after the second screening for congenital hypothyroidism (CH) resulted positive (bTSH 48 mU/L); the first test was negative. Serum blood tests confirmed the diagnosis of CH (TSH 157 mU/L, FT4 0.96 ng/dl, FT3 8.44 pg/ml, negative thyroid autoimmunity). Thyroid ultrasound showed a gland of normal size. Therefore, we started therapy with levothyroxine (L-T4) at the dosage of 10.6 mcg/kg/day. TSH rapidly decreased and we consequently dropped L-T4 dosage. However, free thyroid hormone levels remained high (see table below): therefore, we stopped L-T4 within a month of starting it.

In the suspicion of thyroid hormone resistance, we requested a genetic study of the genes responsible for CH. Interestingly, next-generation sequencing (NGS) revealed heterozygous alterations in two pivotal genes: THRB and TG. Of particular note was the c.727C>T substitution within exon 7 of the THRB gene, a known pathogenic variant associated with thyroid hormone resistance, which led to the diagnosis of Refetoff syndrome. Meanwhile, the c.3272°A>G mutation in TG exon 14 remained a variant of uncertain significance. During follow-up, thyroid function tests remained stable even without L-T4, with adequate growth in length and weight and regular neurocognitive development. At clinical examination we reported heart rate of 120-150 bpm while crying, considered normal for age. From the age of nine months, the patient began to experience episodes of sinus tachycardia during febrile episodes, with heart rate up to 240 bpm. We further investigated it by performing a 24-hour Holter ECG confirming sinus rhythm, devoid of significant arrhythmias or pauses. In light of the symptomatology compatible with the syndrome and considering the uncertain evolution towards cardiac rhythm alterations, we started specific therapy with 3,3’,5-triiodiothyroacetic acid at 30 mcg/kg/day. To conclude, the diagnosis of Refetoff syndrome can be challenging: we must think about it whenever we see persistently high levels of free thyroid hormones without TSH inhibition. Moreover, we must underline the importance of personalized and multidisciplinary management in such enigmatic cases.