SUN-LB097 Thyroid Hormone Resistance Simulating Graves Disease

Abstract

Background: Thyroid hormone actions are mediated by nuclear receptors, thyroid receptor TRα and TRβ encoded by THRA and THRB. Resistance to thyroid hormone (RTH) is characterized by elevated thyroid hormone (TH) along with non-suppressed thyroid-stimulating hormone (TSH). Approximately 85 percent of cases are due to a defect in the THRβ gene (RTH-β). The clinical spectrum ranges from isolated biochemical abnormalities to hyperthyroidism or hypothyroidism. Case description: An adolescent female was initially evaluated by an outside endocrinologist at age 15 for hand tremors, tachycardia, and hypertension. She was diagnosed with hyperthyroidism and treated with methimazole in escalating doses without complete symptom remission. In reviewing her records, thyroid function tests had been abnormal since age 3.5 years with high total T4 (TT4) 20.3 ng/dl, high total T3 (TT3) 294 ng/dl, and normal TSH 3.6 µIU/mL. Iodine-123 uptake was 41% at 24 hours, slightly elevated. No treatment had been prescribed before age 15. Family history revealed that father & multiple paternal relatives had high levels of thyroid hormones but no apparent symptoms of hyperthyroidism. Mother, MGM and maternal aunt had hypothyroidism. The proband’s physical exam was notable for normal pulse and blood pressure and a prominent goiter. Thyroid function tests while taking up to 25 mg methimazole daily showed markedly elevated TT4 20.3 ng/dl, TT3 254 ng/dl, progressively rising TSH (3.6 up to 10 µIU/ml), normal TBG 22 µg/ml and negative titers to TSH receptors, TSI, and anti-thyroid peroxidase antibodies. Due to intermittent tachycardia to 200 bpm, atenolol was increased from 25 to 50 mg/day. Cardiac evaluation showed no intrinsic abnormalities. The gradual tapering of methimazole resulted in increasing TT4 and TT3 with normalization of TSH. Repeat I-123 uptake obtained 1 month after discontinuing methimazole was markedly elevated at 24h (75%). Estimated thyroid weight was 40 grams. Genotyping was heterozygous for the c.1313G>A (p.Arg438His), a known pathogenic variant in the THRβ gene. Conclusion: Resistance to thyroid hormone should be suspected in the setting of variable symptoms of hyperthyroidism, abnormally high serum levels of thyroid hormone with non-suppressed TSH, and negative Graves’ disease antibodies. Elevated I-123 uptake may be found in RTH, but also may have been caused by prior methimazole treatment. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.