title: Differentiated thyroid cancer in patients with resistance to thyroid hormone syndrome. A novel case and a review of the literature.
abstract: Resistance to thyroid hormone (RTH) represents a syndrome in which patients present elevated circulating thyroid hormones in the presence of non-suppressed TSH. We report a novel case where a patient with RTH presented a differentiated thyroid cancer. A19 year-old female had been referred due to thyroid disease that disclosed features characteristic of a RTH. During the follow up it was detected a follicular tumor that led to the recommendation for thyroid surgical ablation, where an incidental papillary thyroid microcarcinoma (mPTC) was found. The increase of thyroglobulin (TG) levels following thyroid removal referred the patient for radioiodine treatment. Post-treatment, it was detected jugular adenopathies and the patient was subjected to cervical lymph node drainage where metastases of the mPTC were found. RTH syndrome was confirmed by the detection of a THRB germline mutation. A BRAF mutation was also found in the mPTC but not detected in the follicular adenoma or normal adjacent tissue. The young age of the patient, the rarity of BRAF mutations in childhood and the high dissemination of the malignancy, lead us to the speculation that increased TSH stimulation in a RTH background and oncogenic activation of BRAF could have served as (co) drivers and might have triggered an advanced stage of the neoplastic disease. These findings together with a review of published cases add novel information to the management of RTH patients with differentiated thyroid cancer.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto Porto, Portugal ; Institute of Biomedical Sciences Abel Salazar (ICBAS) Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar do Porto Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Borges
authors.affiliation: Department of Surgery 2, Centro Hospitalar do Porto Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Costa
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto Porto, Portugal.
authors.forename: Maria Inês
authors.initials: MI
authors.lastname: Alvelos
authors.affiliation: Hospital das Clínicas de Botucatu São Paulo, Brazil.
authors.forename: Glaúcia
authors.initials: G
authors.lastname: Mazeto
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto Porto, Portugal ; Medical Faculty of the University of Porto Porto, Portugal ; Department of Pathology, Centro Hospitalar São João Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto Porto, Portugal ; Medical Faculty of the University of Porto Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
keywords: BRAF; THRB; mPTC; resistance to thyroid hormone; thyroid cancer