Institute of Molecular Pathology and Immunology of the University of Porto Porto, Portugal ; Institute of Biomedical Sciences Abel Salazar (ICBAS) Porto, Portugal.
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar do Porto Porto, Portugal.
Front Mol Biosci. 2014 Sep 2;1:10. doi: 10.3389/fmolb.2014.00010. eCollection 2014.
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.
甲状腺激素抵抗（RTH）是一种综合征，患者在 TSH 未被抑制的情况下循环甲状腺激素升高。我们报告了一例 RTH 患者表现为分化型甲状腺癌的新病例。一名 19 岁女性因甲状腺疾病就诊，该疾病表现出 RTH 的特征。在随访过程中发现了一个滤泡性肿瘤，建议进行甲状腺手术消融，在此过程中发现了一个偶然的甲状腺乳头状微小癌（mPTC）。甲状腺切除术后甲状腺球蛋白（TG）水平升高，提示患者进行放射性碘治疗。治疗后，发现颈静脉淋巴结转移，患者接受了颈部淋巴结引流，发现 mPTC 转移。通过检测 THRB 种系突变证实了 RTH 综合征。在 mPTC 中也发现了 BRAF 突变，但在滤泡性腺瘤或正常相邻组织中未检测到。患者年龄较小，儿童期 BRAF 突变罕见，恶性程度高，我们推测 RTH 背景下 TSH 刺激增加和 BRAF 致癌激活可能作为（共同）驱动因素，并可能引发了肿瘤疾病的晚期阶段。这些发现以及对已发表病例的回顾为 RTH 合并分化型甲状腺癌患者的治疗提供了新的信息。
