Endocrine Abstracts

Introduction: Thyroid Hormone Resistance (THR) is a rare autosomal dominant condition of impaired sensitivity to thyroid hormone. We present an interesting case of thyroid receptor beta (THRB) resistance.

Case Report: A 54-year-old lady presented to the endocrinology clinic with abnormal thyroid function tests (TFTs). TFTs were done as part of the assessment for newly diagnosed atrial fibrillation. She was found to have raised Free T3 and T4 with thyroid stimulating hormone (TSH) in the high normal range. She was intentionally trying to lose weight through diet and exercise. She denied any other hyperthyroid symptoms. She has a history of hypertension, osteoarthritis, and Barrett’s oesophagus. She reported that her father had thyroid receptor problems. Over the year, her free T3 was between 7.8-11.3 pmol/l (range- 3.5-6.5), free T4 between 29.3- 37.8 pmol/l (range- 11.5-22.7), and TSH between 0.7-3.14 miU/L (range- 0.49-5.23). She had negative thyroid receptors and anti-thyroid peroxidase antibodies. Because of her family history, she was referred for genetic testing. Genetic testing using Sanger sequencing method which analyzed mutation surveyors of axons 7,8,9 and 10 of the THRB showed a heterozygous pathogenic missense variant for the THRB gene. Her TFTs were monitored, however, she was not started on any anti-thyroid medications. Genetic testing for this mutation in the family members was planned.

Discussion: Syndromes of reduced sensitivity to thyroid hormone encompass defects interfering with the biological activity of thyroid hormone. Approximately 170 mutated THRB variants have been reported. Monoallelic THRB variants cause autosomal dominant thyroid hormone resistance. There is a 50% risk of transferring pathogenic variants to children.

Learning Points: 1. Obtaining a family history is crucial in diagnosing thyroid hormone resistance, as a positive family history will direct correct investigations and early diagnosis. 2. Correct diagnosis of thyroid hormone resistance prevents unnecessary treatment with antithyroid medications.