ETA2024 Oral Presentations Oral Session 5: Thyroid dysfunction-1 (7 abstracts)
Cardiovascular risk and mortality in a large italian cohort of patients with resistance to thyroid hormone β (RTHβ)
Irene Campi 1 , Simona Censi 2 , Flavia Prodam 3 , Luisa Petrone 4 , Giulia Brigante 5 , Tommaso Porcelli 6 , Rosaria Maddalena Ruggeri 7 , Maria Cristina Vigone 8 , Giuditta Rurale 9 , Serafino Lio 10 , Carla Pelusi 11 & Luca Persani 12
1Irccs, Istituto Auxologico Italiano, Department of Endocrine and Metabolic Diseases, Milan, Italy; 2University of Padua, Endocrinology Unit, Department of Medicine (Dimed), Padua, Italy; 3University of Piemonte Orientale, Unit of Endocrinology; Department of Health Sciences, Novara, Italy; 4Careggi Hospital, Endocrinology Unit, Medical-Geriatric Department, Florence, Italy; 5University of Modena and Reggio Emilia, Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, Modena, Italy; 6University of Naples Federico Ii, Department of Public Health, Naples, Italy; 7University of Messina, Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood Detev, Messina, Italy; 8Irccs San Raffaele Scientific Institute, Endocrine Unit, Department of Pediatrics, Milan, Italy; 9Irccs Istituto Auxologico Italiano, Department of Endocrine and Metabolic Diseases, Milan, Italy; 10Oderzo Hospital, Aulss N.2-Marca Trevigiana, Endocrine Section, Department of Medicine, Oderzo, Italy; 11Alma Mater Studiorum University of Bologna, Department of Medical and Surgical Sciences (Dimec), Irccs Azienda Ospedaliero-Universitaria di Bologna, Division of Endocrinology and Diabetes Prevention and Care, Bologna, Italy; 12Irccs Istituto Auxologico Italiano, Department of Endocrine and Metabolic Diseases, Department of Medical Biotechnology and Translational Medicine (Biometra), University of Milan, Milan, Italy
Objective: decreased survival and higher cardiovascular risk have been reported in a UK cohort of RTHβ patients, but there is no evidence from other countries.
Methods: retrospective study of an Italian cohort of RTHβ patients, carrying heterozygous pathogenic variants in the THRB gene and diagnosed in the period between 1984 and 2023. We collected records at diagnosis of 284 cases, whereas longitudinal data were available in 249 RTHβ patients. We studied the impact of thyroid function tests and recognized risk factors for cardiovascular disease (hypertension, dyslipidemia, overweight and diabetes) on overall mortality and major cardiovascular events (MACEs). Publicly available datasets were used to compare these data with those of the general Italian population.
Results: The variants identified in this cohort are included in the three hot spot clusters of the THRB gene. Hyperkinetic arrythmias were the most common manifestation, with a prevalence of sinus/supraventricular tachycardia and atrial fibrillation of 40% and 18%, respectively. A total of 71 MACEs occurred in 47 RTHβ patients (27%) including 15 fatal events, resulting in a premature morbidity and mortality. MACEs and all-cause deaths occurred in RTHβ 6.5 and 11 years earlier than in the reference population. Free-T4 levels 1.6 folds over the upper limit of normal is the threshold significantly associated with premature (<55 years) cardiovascular manifestations. At univariate analysis dyslipidemia, high fasting glucose/diabetes were associated with MACEs, but only hypertension and male gender remained significantly associated with MACEs and atrial fibrillation with mortality at multivariate analysis. Previous thyroidectomy or radioiodine therapy had no significant effect in the prevention of MACE or all-cause mortality.
Conclusions: Italian RTHβ patients have an increased cardiovascular risk, which is higher in men and in those with fT4 levels above 30 pmol/l. As in the general population, lifestyle interventions and/or pharmacological treatments for hypertension, metabolic disorders, and overweight are recommended to lower this risk. Pharmacological trials should be prompted to evaluate the role of betablockers and thyroid hormone analogues for primary prevention.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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