Hipotireoidismo congênito: avaliação da incidência e dos impactos da alteração do ponto de corte na triagem neonatal em Minas Gerais

Abstract

Introduction: Congenital hypothyroidism (CH) causes irreversible intellectual disability if not treated early. From the 1970s, neonatal screening programs enabled the identification and rapid treatment of affected children, preventing their severe sequelae. In the last 20 years, many programs have described an increase in the incidence of HC, mainly after modifications in the protocols, with an increase in the sensitivity of the test. This study aimed to evaluate the evolution of the incidence of HC in Minas Gerais over the years and to evaluate the impacts of reducing the neonatal TSH cutoff point (TSHneo) in state. Methodology: A retrospective analysis of patients with CH screened by the Neonatal Screening Program of Minas Gerais (PTN-MG) between 1994 and 2021 was carried out. The protocol used TSHneo dosage on filter paper, with a cutoff point of 10mUI/L. CH incidence and etiology were assessed, severity was assessed from free T4 values and cases were classified as transient or permanent. The program was evaluated in terms of its coverage and age of patients at the time of screening and at the start of treatment. In addition, a modification was made to the screening protocol with a reduction in the TSHneo cutoff point to 6mUI/L between November 2021 and August 2022. Children diagnosed as a result of this change (group 1) were clinically and laboratory compared with those whose TSHneo was above 10mUI/L (group 2). Sensitivities, specificities, positive (PPV) and negative (NPV) predictive values of different cutoff points were calculated. Results: Between 1994 and 2021, 6,864,719 children were screened and the incidence of CH was 1:3,298, with no changing trend (p=0.0769). There was no significant change in severity or percentage of permanent (p>0.05). The median age of newborns at screening collection reduced from 11 to 5 days (p<0.01) and treatment initiation from 88 to 16 days (p<0.01). Thyroid dysgenesis was responsible for 43.6% of cases of permanent CH. After modifying the cutoff point, 162,730 children were screened and the incidence was 1:1,323, identifying 50 patients who would have been missed by the previous protocol. The 6mIU/L cutoff point had a sensitivity of 100% and a specificity of 99.5%, PPV 11.87% in the first sample and 80% in the second. The cutoff point of 8mUI/L showed 78.9% sensitivity in the first sample, with a PPV of 24.93%. The previously used threshold, 10mIU/L, had low sensitivity in both samples (64% in the first and 59% in the second). Group 1 had significantly fewer symptoms (p=002), lower serum TSH (median 14.52μUI/mL versus 177.7 μUI/mL, p<0.01) and higher free T4 (median 1.14ng/dL versus 0.56ng/dL, p<0.01) compared to group 2. At ultrasonography, 83.3% of patients in group 1 had no identified thyroid abnormalities. Conclusion: In Minas Gerais, the incidence of CH, its severity and the percentage of permanent cases remained stable between 1994 and 2021. The proportion of dysgenesis in the state is lower than what is classically reported in the literature. There was a significant improvement in the ages at screening and starting treatment over the period. Reducing the TSHneo cutoff point from 10 to 6mUI/L provided an increase in sensitivity, with a predominance of mild cases. However, for the first sample, the PPV was considered too low and inappropriate for a public health program. The TSHneo cutoffs of 8mIU/L in the first sample and 6mIU/L in subsequent samples, when indicated, were more suitable for including more diagnoses, with an acceptable increase in false positives.