Endocrine Abstracts

Introduction: Resistance to thyroid hormone (RTH) is an autosomal dominant condition with mutation of thyroid hormone receptor beta (THR-β) gene. We present 2 cases with unusual thyroid picture posing challenge to diagnosis.

Case 1: 31-year-old lady presented with 6-month history of anxiety, tremors, insomnia and headache. She suffered from asthma and had a family history of hyperthyroidism. On examination, she was overweight (BMI 28kg/m2), tachycardic, tremulous. Cardiovascular examination was normal, smooth palpable goitre, no eye signs. Biochemistry revealed high fT4 57.4 pmol/l (RR 11-23), fT3 17.6 pmol/l (3.5-6.5), TSH 9.75mU/l (0.35-5.5); positive TPO antibodies, absent heterophile antibodies, unremarkable MRI pituitary. Genetic analysis confirmed RTH. 9years later, she was commenced on TRIAC (triiodothyroacetic acid) with symptomatic improvement at 24weeks but had weight gain. 5years later, she developed diabetic ketoacidosis and discontinued TRIAC.

Case 2: 26-year-old lady presented with one-year history of tiredness, fatigue, palpitations and hypersomnia. She suffered from depression and had a family history of hyperthyroidism. On assessment, she was overweight (BMI 19.4 kg/m2), normal cardiovascular examination, no palpable goitre, or ophthalmic signs. Biochemistry revealed high fT4 29.8 pmol/l, fT3 9 pmol/l, non-supressed TSH 2.76mU/l, normal pituitary profile and alpha subunit. Familial dysalbuminaemic hyperthyroxinaemia screen and heterophile antibodies negative. MRI head was normal. Genetic testing was heterozygous for THR-β gene mutation, confirming RTH-beta. Trial of beta blockers was unsuccessful. TFT’s were monitored with no intervention. Next step is to screen first-degree relatives with similar TFT’s.

Discussion: RTH should be suspected with elevated fT4 and fT3 with normal/high TSH and minimal symptoms of thyroid dysfunction. Differentials include TSH-secreting pituitary adenoma, RTH and heterophile antibodies. Treatment depends on predominant symptoms with thyroid hormone replacement, beta-blockers, TRIAC or a combination.

Conclusion: Our two cases showcase the challenges with diagnosis and management. Prompt diagnosis is dependent on clinical suspicion and systematic clinical and biochemical evaluation.