Abstract
Background: Resistance to thyroid hormone (RTH) is an inherited syndrome characterized by reduced responsiveness of target tissues to thyroid hormone. Incidence rate is about 1/40,000 live births [1]. RTH is due to defect in the thyroid hormone receptor, most common is being beta gene (THRB). It is not unusual to be confused with hyperthyroidism. We present a case of RTH with novel mutation which was wrongly managed by primary care provider (PCP) as hyperthyroidism. Case Presentation: 42 year old female was referred to Endocrine clinic by PCP for hyperthyroidism and thyroid nodule. She was initially presented to PCP with lethargy, constipation and neck pain. Ultrasound neck showed left thyroid nodule of 2 cm and lab tests showed TSH 3.14 uIU/ml (0.3-4.0), free T4 3.6 ng/dl (0.9-1.7) and free T3 5.3 pg/ml (2.1-4.4). She was started on Methimazole and propranolol. She had FNA of left thyroid nodule and was benign cytology. She stopped Methimazole after few months due to extreme lethargy and weight gain. Careful history in endocrine clinic explored that her mother had thyroid cancer, was evaluated in National Institute of Health (NIH) for abnormal thyroid hormones and was diagnosed with thyroid hormone resistance. Further testing on family revealed that she also had similar problem. She used to take cytomel several years ago and later stopped due to tachycardia. She had intermittent fatigue, constipation and palpitations. She had regular menstrual cycles, stable weight and no heat or cold intolerance. Pulse was 95 bpm. She had normal size thyroid gland, normal deep tendon reflexes and no tremors. Repeat lab tests showed TSH 4.60 uIU/ml (0.36-3.74), free T4 2.33 ng/dl (0.76-1.46), free T3 7.74 pg/ml (2.18 -3.98). Antibodies were TPO Ab 1.8, TSI < 89% (<140), Anti Tg Ab 0.9 IU/ml (0.0 - 4.0). THBG was 27 ug/ml (13-39). Alpha subunit was 0.40 ng/dl (<1.02). Genetic test revealed novel mutation in THRB gene, NM_000461.4:c.1362G>T (p.Leu454Phe). It was reported as a novel autosomal dominant missense variant in the THRB gene and was considered as pathogenic. Conclusion: Patients with RTH are usually asymptomatic even with high free T4 and free T3. TSH will be slightly high or normal due to failure to suppress hypothalamic-pituitary- thyroid axis. Most common clinical findings include goiter, hyperactivity and tachycardia.Tachycardia can present as heart predominantly expresses alpha isoform of the thyroid hormone receptor [2]. It may be mistaken with diagnosis of hyperthyroidism. Error in treatment with anti-thyroid agents or radioactive iodine ablation or thyroidectomy can be problematic. Reference 1. Lafranchi SH, Snyder DB, Sesser DE, et al. Follow up of newborns with elevated screening T4 concentrations. J Pediatr 2003; 143:296 2. Weiss RE, Murata Y, Cua K, et al. Thyroid hormone action in liver, heart and energy expenditure in thyroid hormone receptor beta deficient mice. Endocrinology 1998;139:4945