Endocrine Abstracts

Background: Resistance to thyroid hormone (RTH) is a rare autosomal dominant condition of altered tissue responsiveness to thyroid hormone (TH) characterised by elevated serum FT₄ and FT₃ and non-suppressed TSH levels caused by mutation in the thyroid receptor (TR) β gene. Different isoforms of TR are expressed in the heart and regulate genes that encode structural and regulatory proteins. The syndrome is characterised by a variable clinical phenotype and clinical manifestations may be non-specific or absent. We report a case of RTH due to TR β receptor mutation presenting with atrial fibrillation and dilated cardiomyopathy.

Case report: A 43-year-old man presented with palpitations and congestive cardiac failure due to atrial fibrillation. He had no other symptoms of thyrotoxicosis. Clinical examination revealed a small goitre but no other features of hyperthyroidism. Echocardiography showed severe global systolic impairment. Thyroid function showed TSH 4.47 mIU/l (Ref 0.27–4.2), FT₄ 27.5 pmol/l (Ref 10–21)), FT₃ 6.7 pmol/l (Ref 3.5–6.5). TBII and TPO antibodies were negative. Alcohol intake was 30 Units/week. Thyroid biochemistry was suggestive of RTH. Assay interference due to heterophil antibodies was excluded by checking TFT’s on a different analytic platform. Pituitary MRI excluded a TSH secreting tumour. The patient was managed medically with bisoprolol, digoxin, ramipril and warfarin and repeat echocardiography showed significant improvement in ventricular function. Genetic studies confirmed a heterozygous point mutation in the ligand binding domain of the TH receptor-β gene confirming RTH.

Discussion: Clinical manifestations of RTH are variable due to heterogeneity of factors that modulate action of TH. Animal models of RTH have shown reduced myocardial contractility. We postulate that hyperthyroxinaemia due to RTH resulted in dilated cardiomyopathy that was exacerbated by alcohol excess. The effects of RTH on circulatory parameters and alterations in ventricular characteristics need further exploration.