SUN-546 Coexistent Resistance to Thyroid Hormone Beta and Viral Thyroiditis

Abstract

Background Resistance to thyroid hormone beta (RTHbeta) is a rare genetic disorder caused by a defective beta form of the thyroid hormone receptor and is characterized by elevated T3 and T4, non-suppressed TSH and variable tissue resistance to thyroid hormone (TH). In most cases a heterozygous mutation in THRB gene is identified. Clinical case A 32 year old adopted Caucasian woman presented with chest pain in the primary care setting in December 2016. Associated symptoms included palpitations, insomnia, poor concentration, restlessness, tremor, mood swings, headaches, irritability, increased appetite, dry scalp, cold extremities, weight gain and diarrhoea. She had no goitre. Based on thyroid function test (TFT) results, she was suspected to have hyperthyroidism and was commenced on antithyroid drugs for 13 months, but treatment was later stopped due to mouth ulcers. At this stage, further tests in our hospital showed elevated fT3 (8.4 pmol/L, RR 3.5-6.5 pmol/L) and fT4 (33.5 pmol/L, RR 10.0-19.8 pmol/L) and non-suppressed TSH (1.35 mU/L, RR 0.35-5.50 mU/L), without evidence of assay interference. SHBG and MRI pituitary were normal. THRB sequencing identified a heterozygous pathogenic mutation (R438H). She further reported that she struggled in school which prevented her from completing university education and remembered that her biological mother had learning disability. She was further assessed in our clinical research facility. Surprisingly, TFT results were very different: fT3 23.6 pmol/L, fT4 97.3 pmol/L and fully suppressed TSH (<0.03mU/L). Resting energy expenditure (REE) measured by indirect calorimetry was markedly raised [0.214 MJ/kg of lean body mass (LBM)]; compared to that seen in healthy controls (mean (SD): 0.148 (0.013) MJ/kg LBM). Given a recent coryzal illness and negative TRAB, thyrotoxicosis was deemed to be in keeping with thyroiditis. The TFT pattern evolved, without treatment, to mild hypothyroidism (fT3 6.8 pmol/L, fT4 16.2 pmol/L and TSH 21.54 mU/L), then returned to the pattern at presentation: elevated fT3 and fT4 and non-suppressed TSH (fT3 10.6 pmol/L, fT4 31.6 pmol/L, TSH 2.09 mU/L). Given ongoing thyrotoxic symptoms, identical to those present at time of referral, Tri-iodothyroacetic Acid (TRIAC) was commenced. Conclusion Coincident thyroid dysfunction can further complicate interpretation of TFTs in patients with RTHbeta. Notably, individuals with RTHbeta and coexistent thyrotoxicosis can exhibit a suppressed TSH, with underlying pituitary resistance to TH action only becoming evident once TH levels fall. Although thyroiditis rarely complicates RTHbeta, it has been reported that autoimmune thyroid disease occurs more commonly, so interpretation of such unusual TFT patterns may be required during the course of management of these individuals.