Heterozygote Advantage of the Type II Deiodinase Thr92Ala Polymorphism on Intrahospital Mortality of COVID-19.

CONTEXT: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and pulmonary fibrosis. OBJECTIVE: Our objectives were to evaluate were cumulative mortality during admission according to Thr92Ala-DIO2 polymorphism. METHODS: Here we conducted an observational, longitudinal, and prospective cohort study to investigate a possible association between the Thr92Ala-DIO2 polymorphism and intrahospital mortality from COVID-19 in adult patients admitted between June and August 2020. Blood biochemistry, thyroid function tests, length of stay, comorbidities, complications, and severity scores were also studied according to Thr92Ala-DIO2 polymorphism. RESULTS: In total, 220 consecutive patients (median age 62; 48-74 years) were stratified into 3 subgroups: Thr/Thr (n = 79), Thr/Ala (n = 119), and Ala/Ala (n = 23). While the overall mortality was 17.3%, the lethality was lower in Ala/Thr patients (12.6%) than in Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The heterozygous genotype (Thr/Ala) was associated with a 47% reduced risk of intrahospital mortality whereas univariate and multivariate logistic regression adjusted for multiple covariates revealed a reduction that ranged from 51% to 66%. The association of the Thr/Ala genotype with better clinical outcomes was confirmed in a metanalysis of 5 studies, including the present one. CONCLUSION: Here we provide evidence for a protective role played by Thr92Ala-DIO2 heterozygosity in patients with COVID-19. This protective effect follows an inheritance model known as overdominance, in which the phenotype of the heterozygote lies outside the phenotypical range of both homozygous.

Carcinoma papilífero de tireoide pediátrico associado à fusão gênica RET-PTC6: relato de caso / Pediatric papillary thyroid carcinoma associated with RET-PTC6 gene fusion: a case report

Introdução: o carcinoma papilífero de tireoide é a neoplasia maligna que mais acomete o sistema endócrino, correspondendo a cerca de 90% dos casos. Diante de sua frequência, nas últimas décadas, foi registrado um aumento do número de casos na população pediátrica e, devido a isso, o número de crianças e adolescentes submetidos à tireoidectomia se tornou cada vez maior. Enquanto as alterações gênicas mais encontradas em adultos com carcinoma papilífero concentram-se em mutações pontuais, na população pediátrica as fusões gênicas são mais frequentes, com destaque para os rearranjos RET/PTC. Objetivo: relatar aspectos clínico-patológicos do carcinoma papilífero de tireoide, associado à fusão do gene RET, em criança submetida à tireoidectomia e radioiodoterapia adjuvante. Em seguida, discute-se a importância do diagnóstico molecular na escolha de terapias relevantes no tratamento do CPT. Caso Clínico: trata-se de uma paciente do sexo feminino, 11 anos de idade, submetida a tireoidectomia total e esvaziamento cervical após diagnóstico do referido carcinoma. O estudo anatomopatológico revelou um carcinoma metastático em linfonodos regionais. Utilizou-se uma amostra de tecido em bloco de parafina para a realização de um sequenciamento de nova geração, que apontou a existência da fusão gênica TRIM24-RET. Conclusão: os dados deste relato de caso evidenciam que a mutação RET/PTC6 está muito associada à população pediátrica e que testes moleculares, como o NGS, são de extremo valor na identificação dessas alterações gênicas e, consequentemente, na terapia a ser adotada para cada paciente.

Introduction: thyroid papillary carcinoma is the malignant neoplasm that most affects the endocrine system, corresponding to about 90% of cases. Given its frequency, in recent decades, there has been an increase in the number of cases in the pediatric population and, as a result, the number of children and adolescents undergoing thyroidectomy has become increasingly larger. While the most common gene alterations found in adults with papillary carcinoma are concentrated in point mutations, in the pediatric population gene fusions are more frequent, with emphasis on the RET/PTC rearrangements. Objective: to report clinical and pathological aspects of papillary thyroid carcinoma associated with RET gene fusion in a child undergoing thyroidectomy and adjuvant radioiodine therapy. Then, the importance of molecular diagnosis in choosing relevant therapies in the treatment of PTC is discussed. Clinical Case: this is an 11-year-old female patient who underwent total thyroidectomy and neck dissection after diagnosis of the aforementioned carcinoma. The anatomopathological study revealed a metastatic carcinoma in regional lymph nodes. A tissue sample in paraffin block was used to perform a new generation sequencing, which showed the existence of the TRIM24-RET gene fusion. Conclusion: the data in this case report show that the RET/PTC6 mutation is closely associated with the pediatric population and that molecular tests, such as the NGS, are extremely valuable in identifying these genetic alterations and, consequently, in the therapy to be adopted for each patient.