FRI472 Thyroid Hormone Resistance β (RTH- β) Syndrome In Patient With Multiple-system Atrophy Parkinsonian Type (MSA-P)

Abstract

Abstract Disclosure: S. Lio: None. M. Albin: None. I. Campi: None. L. Persani: None. Background: Resistance to thyroid hormone β (RTHβ) is a rare dominantly inherited condition of impaired tissue responsiveness to thyroid hormones (TH) due to variants in the THRB gene encoding the TH receptor β (TRβ). RTHβ patients display a distinctive biochemical feature of central hyperthyroidism with elevated serum levels of FT3 and FT4 and unsuppressed TSH. Unfortunately, this syndrome is sometimes misdiagnosed as primary hyperthyroidism, with a delayed diagnosis or inappropriate treatments. Clinical Case: A 72-year-old lady was diagnosed elsewhere in 2010 with atrial fibrillation (AF) and parkinsonian multisystem atrophy (MSA-P), an orphan disease causing progressive autonomic and motor impairment. The patient reported an unspecified dysthyroidism discovered during the diagnostic work-up of AF, but no further investigations were performed. Bisoprolol, Edoxaban and Levodopa/Benserazide were started. In 2020 she had multiple hospitalization due to fall-related injuries, and multiple rib fractures. A neurological and cardiological reassessment did not highlight new problems, nor MSA-P progression, while discrepant thyroid function tests (TFTs) were found (TSH 2.4 mU/L, fT4 3.5 ng/dl, fT3 7.9 pg/ml; normal ranges: 0.4-4.5; 0.8-1.7 and 2.-5, respectively). Anterior pituitary function and a gadolinium-enhanced pituitary MRI were normal. Thyroid ultrasound revealed a modest goiter, with a normal vascularization and multiple hypo-anechoic and spongiform nodules ≤1 cm. Propylthiouracil has been started At referral in our Center, discrepant TFTs were confirmed (TSH 6.6 mU/L, fT4 2.5 ng/dL, fT3 5.1 pg/ml). TPOAb, TgAb and TRAb were absent. We also excluded assay interferences due to heterophiles antibodies. Being T3 administration contraindicated due to AF, a TRH-test, after suspension of PTU, was performed showing an intense and prolonged response of the TSH (36.7 and 19.2 mU/L at 30 and 120 minutes, respectively), consistent with RTHβ. Consistently, molecular analysis by a targeted NGS panel revealed a heterozygous known pathogenic variant in the exon 9 of the TRHB gene (c.1033G>A, p.Gly345Ser). Conclusion: In the differential diagnosis of central hyperthyroidism RTHβ should be considered even in older patients, as late diagnosis may occur. The association of RTHβ with MSA-P has never been reported before, although a causal relationship is improbable. Nevertheless, central hyperthyroidism could worsen underlying neurological diseases, given the critical role of TH in CNS and muscle. A greater awareness of both neurologists and endocrinologists on rare thyroid diseases is warranted, to improve the care of patients with neurological orphan diseases. Presentation: Friday, June 16, 2023