Table 1 Study characteristics of the 10 included studies

Yeap [20], 2012

Australia

Cross-sectional study

3943 men/ Community

75.2 ± 4.1

TSH(0.4–4.0mIU/L), FT4(10–23 pmol/L)

Frailty phenotype criteria: Frail

Nonfrail

Age, BMI, smoke status, diabetes, social support, impairment of seeing or hearing, testosterone and Insulin–like growth factor–I level

Nonsignificant association noted between TSH and frailty (p > 0.5). FT4 had the highest odds for frailty in two quartiles (Q3:Q1, OR = 1.32, 95% CI = 1.01–1.73; Q4:Q1, OR = 1.36, 95% CI = 1.04–1.79; p = 0.010). Neither subclinical hyperthyroidism (OR = 0.69, 95% CI = 0.21–2.31) nor subclinical hypothyroidism (OR = 1.17, 95% CI = 0.90–1.53) was significantly associated with frailty

Virgini [19], 2015

Switzerland

Prospective cohort study

1455 men/ Community

73.6 ± 5.8

Subclinical hyperthyroidism, subclinical hypothyroidism, euthyroidism TSH(0.55–4.78mIU/L), FT4( 0.8–1.75 ng/dL)

Frailty phenotype criteria: Robust group Prefrail and frail group

age, race, BMI and clinicalcenter

Compared with those with euthyroid, men with subclinical hyperthyroidism had an increased likelihood of high frailty status (adjusted OR = 2.48, 95% CI = 1.15–5.34)

Bertoli [21], 2017

Italy

Observational study

112/ 62 hospitalized, 50 outpatient

79.1 ± 7.0

TSH(0.35–4.5μIU/mL), FT4(0.8–1.75ng/dL), FT3(2.3–4.2 pg/mL)

Frailty score

NA

Frailty score was significantly correlated with FT3 (p < 0.0001), but not FT4 (p = 0.1974)

Veronese [14], 2017

Italy

2571 cross-sectional, 1732 longitudinal

3099 (1245 men, 1854 women)/ community

Men 73.2 ± 6.5

Women

74.7 ± 7.3

TSH (0.3 and 4.2 mUI/L)

Quintiles cutoffs for men: 0.7, 1.0, 1.3, and 2, while for women 0.8, 1.1, 1.5, and 2.5 mUI/L

Frailty phenotype criteria:

Frail

Nonfrail

Age, BMI, smoke status, alcohol drinker, education, monthly income, ADL, geriatric depression, MMSE scores, Charlson comorbidity score, eGFR, number of drugs

With the third quintile of serum TSH (Q3) as the reference group, the highest quintile (Q5) was associated with the highest frailty risk in men (OR = 1.55, 95% CI = 1.03–2.33) and in women (OR = 1.97, 95% CI = 1.59–2.45)

Bano [8], 2018

Netherlands

Prospective cohort study

9,640/ NA

64.9 ± 9.7

TSH (0.40 to 4.0 mIU/L), FT4( 0.86 to 1.94 ng/dL)

Frailty index: 45-item

age, sex, cohort, smoking, alcohol, and education

TSH (p < 0.0003) and FT4 (p < 0.0001) with frailty at baseline

Pasqualetti [22], 2018

Italy

Longitudinal study

619/ hospitalized

83.8 ± 7.4

TSH(0.4–4.0mIU/L), FT4(0.70–1.70ng/dL), FT3( 2.7–5.0 pg/mL)

MPI score:

 > 0.66 = frailty;

0.34–0.66 = Prefrail

0.34 = Robust

age, sex, MPI, FT3, LDH, Hb, CRP and albumin

MPI score was inversely and strongly correlated with FT3 (p < 0.001) and moderately and positively correlated with FT4 (p < 0.05)

Arosio [23], 2020

Italy

Cohort study

593/community or nursing home

80.1 ± 15.7

TSH(0.27–4.2µIU/ml), FT4(0.9–1.7ng/dl), FT3(2.3–4.4 pg/ml)

Frailty index:

30 items

sex, age and study center

Correlation of frailty index with FT3 (ρ = − 0.281, p < 0.001), TSH (ρ = − 0.223, p = 0.003) was negative

Correlation of frailty index with FT4 was positive (ρ = 0.189, p = 0.001)

Xiu [24], 2020

China

Cross-sectional study

240 (T2DM)/ NA

68.9 ± 6.9

TSH(0.55–4.78mIU/mL), FT4(0.89–1.76ng/dL), FT3(2.3–4.2 pg/mL)

Frailty phenotype criteria:

Frail

Prefrail

Robust

age, sex, 25(OH) D3, eGFR, FT3

Logistic regression showed that low FT3 was significantly associated with an increased risk of frailty (OR = 4.53, 95% CI = 1.89–10.83; P = 0.001)

Bhalla [25], 2021

USA

Cross-sectional study

150/ inpatients

70.0 ± 6.2

TSH(0.5-5µIU/ml), FT4(0.70–1.48ng/dL), FT3(1.50–4.20 pg/ml)

Frailty index: 30 items

age

Patients with lower TSH (0.31 ± 0.11 µIU/mL) had higher mean frailty index (0.25 ± 0.12), and patients with normal TSH (1.84 ± 0.84 µIU/mL) had lower mean frailty index (0.15 ± 0.07; p < 0.001)

An association of FT3 levels with FI was inverse (p = 0.13), and it disappeared when age was adjusted for (p = 0.4)

Liu [26], 2021

China

Cross-sectional study

146/ inpatients

85.0 ± 8.2

TSH(0.35–4.94mIU/L), FT4(9.01–19.05pmol/L), FT3(2.63–5.70pmol/L), T4(62.88–150.80 nmol/L), T3(0.88–2.44 nmol/L)

Frailty phenotype criteria:

Frail

Prefrail

Robust

age, sex, BMI, smoking, and HbA1c

Frailty was significantly associated with serum TSH (OR = 1.258) and T3 (OR = 0.102) levels