Thyroid hormone resistance in identical twins.

A 62 year man with tablet-controlled type 2 diabetes was referred by his general practitioner to the emergency medical unit with shortness of breath. He was found to be in atrial fibrillation with a heart rate of 130 beats/min and the patient was commenced on sotalol and warfarin. Thyroid function tests were requested and found to be abnormal, with thyroid-stimulating hormone (TSH) 7.75 mU/l (reference range 0.35–4.5), raised serum thyroxine (FT 4) 49.3 pmol/l (11–24) and triiodothyronine (FT 3) 10.3 pmol/l (3.9–6.8). On re-examination, the patient did not have a goitre or any clinical features of hyperthyroidism other than atrial fibrillation. A differential diagnosis of assay interference, a TSH secreting pituitary adenoma or thyroid hormone resistance was considered. Samples were sent for repeated analysis in a second laboratory to look for evidence of assay interference; these confirmed a raised TSH with a raised FT 3 and FT 4. Thyroid antibodies, a thyrotrophin-releasing hormone (TRH) test and pituitary magnetic resonance imaging (MRI) were organized for the patient on an outpatient basis. The patient was discharged from hospital to be followed up by the Endocrine team. Ten days after discharge, the patient represented to the emergency medical unit with headaches, vomiting and slurred speech. Neurological examination revealed dysarthria, horizontal nystagmus, left-sided dysdiadokinesis and past-pointing, reduced coordination in the left lower limb and ataxia. An emergency computed tomography scan of the head showed a left cerebellar infarction. Warfarin was temporarily discontinued, and the patient was commenced on aspirin and dipyrid-amole. He remained in atrial fibrillation and was restarted on warfarin 2 weeks later. The patient was switched from sotalol to digoxin for heart rate control. He improved clinically and was discharged home. The patient was followed up by the Endocrine team. Thyroid peroxidase antibodies were negative. Serum prolactin, follicular-stimulating hormone, luteinising hormone and testosterone were all in the normal range. Random serum cortisol at mid-morning was 301 nmol/l. Glycated haemoglo-bin (HbA1c) was 6.8%. The pituitary MRI showed no abnormality. The TRH test stimulated TSH release: after a 200 mcg intravenous injection of TRH (Protirelin), TSH increased from 4.32 mU/l at baseline to 23.74 mU/l after 30 min and was recorded at 18.44 mU/l after 60 min, consistent with the diagnosis of thyroid hormone resistance. It emerged that the subject had an identical twin with a very similar medical history to himself. The twin lived locally and had insulin-treated type 2 diabetes. He had …