Thyroid hormone resistance from newborns to adults: a Spanish experience

摘要

ObjectiveThyroid hormone resistance (RTH beta) is a rare genetic disorder characterized by an altered response of target tissue to the action of thyroid hormone. Few studies on RTH beta have been carried out in southern European populations. We aimed to describe the clinical and genetic characteristics at the time of diagnosis in a Spanish cohort of patients with genetically confirmed RTH beta, with ages ranging from newborns to adults.MethodsRetrospective multicenter study of 28 patients who were genetically confirmed as RTH beta. Clinical and biochemical data were collected from the reference centers, and the studied variables included age, sex, anthropometric data, clinical characteristics and biochemical results. In the Basque country, a simultaneous analysis of TSH and T4 is carried out in the program for the screening of inborn errors of metabolism. A molecular analysis of the thyroid hormone beta (THRB) gene was performed.ResultsThe total cohort included 20 adults and eight pediatric patients (six newborns). Of the total, 5 (17.8) were diagnosed by clinical characteristics (goiter, hypertension or tachycardia), 13 (46.4) were analyzed in the context of a family study and 10 (35.7) were diagnosed after obtaining an altered fT4 and/or TSH level in a biochemical analysis performed due to clinical symptoms unrelated to RTH beta. Four of the newborns included in the series were diagnosed by the result of neonatal screening, which allows us to estimate a minimum local incidence of RTH beta of 1/18,750 live newborns. The genetic analysis showed the presence of 12 different heterozygous mutations in the THRB gene.ConclusionsWe report the clinical and genetic characteristics of a Spanish RTH beta cohort, from neonates to adults. We also describe one novel mutation in the THRB gene as the cause of the disease. The simultaneous analysis of TSH and T4 carried out in the program for the screening of inborn errors of metabolism facilitates the early diagnosis of RTH beta in newborns and has allowed us to estimate a minimum local incidence of RTH of 1/18,750 live newborns.