Endocrine Abstracts

Case history: A 42 year old male teacher presented to the emergency department with an acute right MCA infarct, on a background of paroxysmal atrial fibrillation/flutter and recurrent supraventricular tachycardia. He had chronic palpitations, with previous failed cardiac ablation. He had no other medical history, specifically, no history of ear infections or learning difficulties. There was no known family history of thyroid dysfunction. Previous TSH levels (no FT4 measurements were recorded) were within the normal range.

Investigations: CT brain and angiogram on admission showed an acute right MCA infarct. He was in atrial fibrillation. Repeat thyroid function testing (Roche assay) revealed a discordant pattern; TSH 5.7 mIU/l (0.27–4.2), FT4 34.5 pmol/l (12–22), FT3 7.9 pmol/l (3.1–6.8). Assay interference was excluded by measuring thyroid hormones (TH) on alternate assays [Delfia; TSH 4.16 mIU/l (0.4–4.0), FT4 41.3 pmol/l (9–20); Centaur FT3 10.74 pmol/l (3.5–6.5)], and by demonstrating expected responses to dilution and PEG precipitation of TSH and FT4. SHBG was normal (24.2 nmol/l, RR 16.5–55.9). ALB gene sequencing identified no mutations, however, sequencing of the gene encoding the ? form of the thyroid hormone receptor (THRβ) revealed a heterozygous mutation; M313T, known to be pathogenic, and hence confirming Resistance to Thyroid Hormone β.

Management: Initial stroke management included iv thrombolysis but later he developed a further acute cerebral infarct requiring thrombectomy, complicated by haemorrhagic transformation. He had persistent paroxysmal atrial fibrillation, which was difficult to control (no improvement with dronedarone, treated with increasing doses of metoprolol and flecainide). He has significant residual neurological deficits and required prolonged admission to a rehabilitation facility. Given his relative cardiac thyrotoxicosis, he was commenced on carbimazole 10mg od (TRIAC was not available), with biochemical (FT4 reduction from 33.4 pmol/l to 22.1 pmol/l) and clinical improvement (reduced palpitations and ongoing neurological recovery).

Conclusions and points for discussion: This case highlights the need for screening with both T4 and TSH to exclude thyroid dysfunction in patients with a high suspicion of thyroid disease. Patients with RTHβ are known to have tachycardia, and carry a risk of atrial fibrillation. Although there may be some protection from the pro-thrombotic effects of TH (since these are TRβ mediated), patients have dyslipidaemia and increased HOMA-IR, consistent with metabolic dysfunction. Unusually in RTHβ, this patient had very prominent cardiac symptoms, suggesting pronounced cardiac thyrotoxicosis, and required anti-thyroid drug treatment to control these symptoms. Unfortunately, his predisposition to cardiac arrhythmia likely contributed to the development of cerebrovascular disease, with devastating consequences.