Thyroid hormone resistance index and mortality in euthyroid subjects: Di@bet.es study

in European Journal of Endocrinology
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  • 1 Department of Endocrinology and Nutrition, Hospital Regional Universitario de Málaga/Universidad de Málaga, Instituto de Investigación Biomedica de Málaga-IBIMA, Málaga, Spain
  • | 2 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
  • | 3 UGC de Laboratorio (Bioquímica), Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain
  • | 4 Department of Endocrinology and Nutrition, Hospital Universitario S. Carlos de Madrid, Madrid, Spain
  • | 5 Hospital Universitario Cruces, BioCruces Bizkaia, UPV/EHU, Barakaldo, Spain
  • | 6 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
  • | 7 Department of Endocrinology and Nutrition, Hospital Universitario Central de Asturias/University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
  • | 8 EAP Raval Sud, Institut Català de la Salut, Red GEDAPS, Primary Care, Unitat de Suport a la Recerca (IDIAP – Fundació Jordi Gol), Barcelona, Spain
  • | 9 Department of Endocrinology and Nutrition, Hospital Universitario Cruces – BioCruces Bizkaia – UPV-EHU, Baracaldo, Barcelona, Spain
  • | 10 Diabetes Unit, Hospital Arnau de Vilanova, Valencia, Spain
  • | 11 Genomic Studies and Genetic Diagnosis Unit, Fundación de Investigación del Hospital Clínico de Valencia-INCLIVA, Valencia, Spain

Correspondence should be addressed to Sergio Valdés; Email: sergio.valdes@hotmail.es

(N Colomo and G Rojo-Martínez contributed equally as senior authors)

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Objective

It has been proposed that a mild form of acquired resistance to thyroid hormone may occur in the general population. Its clinical significance remains largely unknown. The objective of the study was to explore whether a newly described thyroid hormone resistance index is associated with the risk of mortality in a sample of community-dwelling euthyroid subjects representative of the adult population of Spain.

Design

Longitudinal observational study including 3750 individuals, free of thyroid disease, TPO antibodies-negative (<50 IU/mL) and with TSH levels within the euthyroid range (≥0.5 and ≤5.0 mUI/mL) participating in the nationwide study Di@bet.es (2008–2010).

Methods

We used the Thyroid Feedback Quantile-based Index (TFQI) as a marker of resistance to thyroid hormone. The study population was grouped into categories according to their TFQI values at baseline. Fatal events were ascertained from the national death registry (end of follow-up December 2016).

Results

A total of 231 deaths were recorded during an average follow-up of 7.3 years. Compared with the category with the highest sensitivity to free thyroxine (TFQI ≤ p5) (reference), the relative risk of mortality in the categories with TFQI > p5 and ≤p25; >p25 and ≤p50; >p50 and ≤p75; >p75 and ≤p95 and >p95 were 1.01, (0.47–2.19), 1.42 (0.68–2.97), 1.54 (0.74–3.22), 1.47 (0.70–3.11) and 2.61 (1.16–5.89), respectively (P for trend 0.003). The association remained significant after multivariate adjustment of the data (P for trend 0.017).

Conclusions

A thyroid hormone resistance index focused on deviations of the average pituitary response to thyroid hormones may be associated with all-cause mortality independently of other conventional risk factors and comorbidities.

 

     European Society of Endocrinology

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