Kopanos Stylianos, Feldkamp Joachim
Academic Department of Endocrinology, Diabetes and Infectiology, Klinikum Bielefeld, Medical School and University Medical Centre, East Westphalia-Lippe Bielefeld University, Teutoburgerstrasse 50, 33604, Bielefeld, Germany.
Eur Heart J Case Rep. 2025 Jul 17;9(8):ytaf338. doi: 10.1093/ehjcr/ytaf338. eCollection 2025 Aug.
Resistance to thyroid hormone (RTH) is a rare genetic disorder caused by mutations in the thyroid hormone receptors α or β (THRα, THRβ) genes, leading to impaired tissue responsiveness to thyroid hormones. While its systemic effects are well-documented, the cardiac manifestations of RTH, including hypertrophic and dilated cardiomyopathy (DCM), arrhythmias, and heart failure, are often underrecognized, particularly in cases of treatment refractory heart failure. This case report aims to highlight the importance of cardiological awareness in diagnosing and managing RTH-related cardiomyopathy.
We report the case of a 50-year-old Caucasian female with a confirmed variant c.1357C > A, p.P453T mutation in the THRβ gene, presenting with recurrent goitre, hypothyroidism, and progressive cardiovascular complications. Her clinical course was marked by episodes of angina-like symptoms, atrial fibrillation, left heart failure, and severe pulmonary oedema, eventually progressing to DCM with an ejection fraction below 30%. Despite optimal guideline-directed medical therapy, her cardiac condition deteriorated, necessitating orthotopic heart transplantation. Genetic testing confirmed the same mutation in her mother, brother, and two sons, highlighting the autosomal dominant inheritance of the disease. Thyroidectomy and lifelong levothyroxine therapy, combined with post-transplant immunosuppression, further complicated her management, underscoring the systemic interplay of RTH with cardiac function.
This case emphasizes the rarity and clinical significance of RTH as a potential aetiology in refractory cardiac failure. Cardiologists should maintain a high index of suspicion for thyroid dysfunction in unexplained or treatment-resistant cardiomyopathy, particularly when associated with familial thyroid disorders or arrhythmias. Early diagnosis and a multidisciplinary approach involving endocrinology and cardiology are essential for improving outcomes and tailored therapeutic strategies for patients with RTH-related cardiomyopathy.
甲状腺激素抵抗（RTH）是一种罕见的遗传性疾病，由甲状腺激素受体α或β（THRα、THRβ）基因突变引起，导致组织对甲状腺激素的反应受损。虽然其全身影响已有充分记录，但RTH的心脏表现，包括肥厚型和扩张型心肌病（DCM）、心律失常和心力衰竭，往往未得到充分认识，尤其是在治疗难治性心力衰竭的病例中。本病例报告旨在强调心脏病学意识在诊断和管理RTH相关心肌病中的重要性。
我们报告了一例50岁的白种女性，其THRβ基因存在确诊的c.1357C>A、p.P453T变异突变，表现为复发性甲状腺肿、甲状腺功能减退和进行性心血管并发症。她的临床病程以心绞痛样症状、心房颤动、左心衰竭和严重肺水肿发作为特征，最终发展为射血分数低于30%的DCM。尽管进行了最佳的指南指导药物治疗，她的心脏状况仍恶化，需要进行原位心脏移植。基因检测证实她母亲及哥哥和两个儿子存在相同突变，突出了该疾病的常染色体显性遗传。甲状腺切除术和终身左甲状腺素治疗，加上移植后免疫抑制，使她的治疗更加复杂，强调了RTH与心脏功能的全身相互作用。
本病例强调了RTH作为难治性心力衰竭潜在病因的罕见性和临床意义。心脏病学家应对不明原因或治疗抵抗性心肌病中的甲状腺功能障碍保持高度怀疑指数，特别是当与家族性甲状腺疾病或心律失常相关时。早期诊断以及涉及内分泌学和心脏病学的多学科方法对于改善RTH相关心肌病患者的预后和制定个性化治疗策略至关重要。
