Degree of Peripheral Thyroxin Deiodination, Frailty, and Long-Term Survival in Hospitalized Older Patients

J Clin Endocrinol Metab. 2018 May 1;103(5):1867-1876. doi: 10.1210/jc.2017-02149.


Context: Although the association between low free triiodothyronine (FT3) and poor outcome has been extensively reported in literature, the degree of peripheral thyroxin deiodination and its relationship with frailty and survival in hospitalized older patients has not yet been fully established. The aim of the current study was to evaluate the possible correlation between FT3/free thyroxine (FT4) ratio reduction, an indirect marker of thyroxin deiodination impairment, and frailty status and survival in hospitalized older patients.

Methods: We consecutively enrolled older patients, hospitalized in the geriatrics ward of the University of Pisa. At admission, Multidimensional Geriatric Assessment (MGA) and Multi Prognostic Index (MPI), an indirect measure of frailty, were obtained from all the patients. Causes of hospitalization and prevalence of delirium were recorded. Blood samples for FT3, FT4, and thyrotropin value evaluation were drawn after an overnight fast.

Results: A total of 643 patients (83.8 ± 7.4 years, 53% women) were studied. FT3 was inversely and strongly correlated, whereas FT4 was moderately positively correlated with MGA parameters, MPI score (P < 0.001 and P < 0.05, respectively), and survival (P < 0.001 and P = 0.09, respectively). FT3/FT4 ratio reduction was highly associated with worse MGA (P < 0.001) and MPI scores (P < 0.0001), even in patients without low FT3. The inclusion of FT3 in the final model of multivariate Cox regression confirmed the independent role of FT3/FT4 ratio in predicting survival (P = 0.005).

Conclusion: Overall, our study documented a strong association between FT3/FT4 ratio reduction, a surrogate marker of peripheral thyroxin deiodination, and frailty. Moreover, FT3/FT4 ratio value emerged as independent marker of survival, even in patients with normal FT3 values.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Frailty / blood
  • Frailty / epidemiology
  • Frailty / metabolism*
  • Geriatric Assessment
  • Halogenation
  • Hospitalization* / statistics & numerical data
  • Humans
  • Italy / epidemiology
  • Life Expectancy*
  • Male
  • Thyroid Function Tests
  • Thyrotropin / blood
  • Thyroxine / blood
  • Thyroxine / metabolism*
  • Triiodothyronine / blood


  • Triiodothyronine
  • Thyrotropin
  • Thyroxine