Serum Thyroid-Stimulating Hormone Levels and

Original Articles

REJUVENATION RESEARCH Volume 20, Number 3, 2017 ª Mary Ann Liebert, Inc. DOI: 10.1089/rej.2016.1872

Serum Thyroid-Stimulating Hormone Levels and Frailty in the Elderly: The Progetto Veneto Anziani Study

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Nicola Veronese,1 Sara Fernando-Watutantrige,2 Stefania Maggi,3 Marianna Noale,3 Brendon Stubbs,4–6 Raffaele Antonelli Incalzi,7 Sabina Zambon,3,8 Maria Chiara Corti,9 Egle Perissinotto,10 Gaetano Crepaldi,3 Enzo Manzato,1,3 and Giuseppe Sergi1

Abstract

High or low thyroid-stimulating hormone (TSH) levels seem to be associated with several negative outcomes in the elderly, but the literature about TSH and frailty is still limited. In this article, we investigated whether TSH is associated with prevalent and incident frailty in a cohort of older community-dwelling subjects. Among 3099 initially screened in the Progetto Veneto Anziani Study, 2571 men and women aged ‡65 years (for crosssectional analyses) and 1732 (longitudinal, mean follow-up period of 4.4 years) were divided into sex-specific quintiles according to baseline serum TSH concentrations within normal range (0.3 and 4.2 mUI/L). Frailty was defined as the presence of three among five Fried’s criteria. At baseline, taking those in the third quintile of serum TSH as reference (Q3) and adjusting for potential confounders, participants in the highest (Q5) quintile had an increased odds ratio (OR) of having frailty (OR = 1.55; 95% confidence interval [CI]: 1.03–2.33 for men; OR = 1.97; 95% CI: 1.59–2.45 for women). Men in Q1 had significant higher odds of having muscle weakness and exhaustion, while those in Q5 had muscle weakness and slow gait speed. Women in Q1 had significantly higher odds of having all the Fried’s criteria (except for exhaustion), while those in Q5 reported a significantly higher presence of muscle weakness and slow gait speed. At follow-up, men in Q5 had an increased risk of frailty (OR = 1.37; 95% CI: 1.02–1.91) similar to women in Q1 (OR = 1.47; 95% CI: 1.21–1.78). In conclusion, men with higher and women with lower serum TSH levels are at increased risk of frailty. Keywords: community-dwelling adults, elderly, frailty, thyroid

Introduction

F

railty is typically defined as a state of increased vulnerability to stressors that results from decreased physiologic reserve in multiple organ systems causing limited capacity to maintain homeostasis.1 It is a highly prevalent condition in older people with an estimated prevalence of 10% in community-dwelling people.2 Frailty is associated

with several deleterious outcomes in the elderly, including higher rate of hospitalization, falls, disability, and mortality.3 There is a growing evidence base to suggest that frailty is characterized by a ‘‘metabolic signature.’’4 Frail subjects are characterized by higher chronic inflammation levels5 and concomitant downregulation of multiple endocrine factors,4 suggesting that these markers could be useful for the early identification of frailty.

1

Geriatrics Division, Department of Medicine (DIMED), University of Padova, Padova, Italy. Endocrinology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy. National Research Council, Neuroscience Institute, Padova, Italy. 4 Health Service and Population Research Department, Institute of Psychiatry, King’s College London, London, United Kingdom. 5 Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, United Kingdom. 6 Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, United Kingdom. 7 Geriatrics-Unit of Respiratory Pathophysiology, Campus Bio Medico University and Teaching Hospital, Rome, Italy. 8 Department of Medicine (DIMED), Clinica Medica I, University of Padova, Padova, Italy. 9 Division of Healthcare Planning and Evaluation of the Regione Veneto, Venice, Italy. 10 Biostatistics, Epidemiology and Public Health Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy. 2 3

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Unfortunately, very few representative studies have assessed the potential relationship between thyroid function (assessed with thyroid-stimulating hormone [TSH]) and frailty. Two cross-sectional studies6,7 reported a nonsignificant association between TSH levels and frailty, although one found an association between free thyroxine and frailty.7 One longitudinal study8 did not find an association of subclinical hyperthyroidism and hypothyroidism with incident frailty in older men. This longitudinal study, however, included very few participants for both hyperthyroidism (n = 22) and hypothyroidism (n = 85). These findings are somewhat surprising since both subclinical hyperthyroidism and hypothyroidism are associated with a high rate of medical conditions significantly associated with frailty as previously mentioned. Previous literature has suggested that in the elderly, thyroid function at the extremes of the normal range could be associated with the onset of several medical conditions.9,10 However, the knowledge of the relationship between TSH and frailty is still limited and worthy of improvement through representative research. We investigated whether TSH is associated with frailty in a cohort of older men and women. We hypothesized that assessing the association between TSH and frailty in both cross-sectional and longitudinal studies of the same population and correcting for potential confounders might provide more definitive evidence about the TSH-frailty relationship. Methods Data source and subjects

The data for this analysis were derived from the Progetto Veneto Anziani (Pro.V.A.), an observational cohort study on the Italian population aged ‡65 years. The study population included 3099 age- and sex-stratified Caucasian participants (1854 women and 1245 men) randomly selected between 1995 and 1997 using a multistage stratification method. Sampling procedures and data collection methods have been described elsewhere.11 This study utilizes information obtained at baseline and at follow-up after 4 years. The local ethics committees of Padova University and the Local Health Units (ULSS) n. 15 and n. 18 of the Veneto Region approved the study protocol, and participants gave their written informed consent. Clinical data

Participants were examined at city hospitals by trained physicians and nurses. Information was collected on their smoking, alcohol drinking, education, and monthly income during a face-to-face interview. Smoking status was classified as ‘‘current’’ versus ‘‘never/former’’ (smoking for at least a year in the past). Alcohol drinking was categorized as ‘‘yes’’ versus ‘‘no’’ in the previous month. Education was categorized as £ versus >5 years, 5 years being the level of primary education in Italy. Monthly income was categorized as ‡ versus