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Free triiodothyronine/free thyroxine (FT3/FT4) ratio is strongly associated with insulin resistance in euthyroid and hypothyroid adults: a cross-sectional study

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Introduction: Insulin resistance (IR) is a key and early pathogenetic mechanism of cardiometabolic diseases with huge potential if being early detected and mitigated, for lowering the burden of the diseases. Available data are conflicting to what extent adult thyroid dysfunction is associated with IR. Therefore, we aimed to investigate the association and to identify which thyroid parameters are predictors of IR. Material and methods: After undergoing basic anthropometric and biochemical studies including thyroid hormones, oral glucose tolerance test (OGTT) and insulin, 1425 middle-aged individuals were divided into three groups according to the thyroid parameters: overt hypothyroidism (OH), subclinical hypothyroidism (SH) and euthyroidism (EU). Results: The homeostasis model assessment of IR (HOMA-IR), fasting insulin and 2-hour glucose levels of OGTT showed a steady, yet insignificant, increase from EU through SH to OH. The strongest noted correlations were those of insulin levels with free triiodothyronine/free thyroxine (FT3/FT4) ratio (r = 0.206, p < 0.001) and FT3 (r = 0.205, p < 0.001). Also in the case of HOMA-IR, the only statistically significant correlations were observed with FT3 (r = 0.181, p < 0.001) and the FT3/FT4 ratio (r = 0.165, p < 0.001). Among other thyroid hormones, linear logistic regression proved the FT3/FT4 ratio as the only significant predictor of HOMA-IR (linear coefficient = 5.26, p = 0.027) and insulin levels (linear coefficient = 18.01, p = 0.023), respectively. Thyroid-stimulating hormone was not associated with IR in either correlation or regression analysis. Conclusions: The FT3/FT4 ratio should be more emphasised in the diagnosis and treatment of thyroid disorders. Patients could benefit from a pharmacological reduction of the FT3/FT4 ratio, potentially leading to a decrease in insulin resistance, and thus a risk of the cardiometabolic diseases.
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Original paper
ORIGINAL PAPER
Free triiodothyronine/free thyroxine (FT3/FT4) ratio
isstrongly associated with insulin resistance in euthyroid
andhypothyroid adults: a cross-sectional study
Ladislav Štěpánek 1, 2, Dagmar Horáková 1, Lubomír Štěpánek3, Vladimír Janout 1,
Jana Janoutová 4, Kateřina Bouchalová 5, Karel Martiník6
1Department of Public Health, Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic
2Department of Occupational Medicine, University Hospital Olomouc and Faculty of Medicine and Dentistry,
Palacký University Olomouc, Olomouc, Czech Republic
3Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Prague, Czech Republic
4Department of Healthcare Management, Faculty of Health Sciences, Palacký University Olomouc, Olomouc, Czech Republic
5Department of Pediatrics, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc,
Olomouc, Czech Republic
6Ambulance Prof. MUDr. Karla Martiníka DrSc. s.r.o, Hradec Králové, Czech Republic
Abstract
Introduction: Insulin resistance (IR) is a key and early pathogenetic mechanism of cardiometabolic diseases with huge potential if de-
tected early and mitigated, for lowering the burden of the disease. Available data are conicting to what extent adult thyroid dysfunction
is associated with IR. Therefore, we aimed to investigate the association and to identify which thyroid parameters are predictors of IR.
Material and methods: After undergoing basic anthropometric and biochemical studies including thyroid hormones, oral glucose tol-
erance test (OGTT), and insulin, 1425 middle-aged individuals were divided into three groups according to thyroid parameters: overt
hypothyroidism (OH), subclinical hypothyroidism (SH), and euthyroidism (EU).
Results: The homeostasis model assessment of IR (HOMA-IR), fasting insulin, and two-hour glucose levels of OGTT showed a steady, yet
insignicant, increase from EU through SH to OH. The strongest noted correlations were those of insulin levels with free triiodothyronine/
/free thyroxine (FT3/FT4) ratio (r = 0.206, p < 0.001) and FT3 (r = 0.205, p < 0.001). Also in the case of HOMA-IR, the only statistically
signicant correlations were observed for FT3 (r = 0.181, p < 0.001) and the FT3/FT4 ratio (r = 0.165, p < 0.001). Among other thyroid
hormones, linear logistic regression proved the FT3/FT4 ratio as the only signicant predictor of HOMA-IR (linear coefcient = 5.26,
p = 0.027) and insulin levels (linear coefcient = 18.01, p = 0.023), respectively. Thyroid-stimulating hormone was not associated with IR
in either correlation or regression analysis.
Conclusions: The FT3/FT4 ratio should be more emphasised in the diagnosis and treatment of thyroid disorders. Patients could benet
from a pharmacological reduction of the FT3/FT4 ratio, potentially leading to a decrease in insulin resistance, and thus a corresponding
decrease in the risk of the cardiometabolic diseases. (Endokrynol Pol 2021; 72 (1): 8–13)
Key words: thyroid disorder; insulin resistance; FT3/FT4 ratio; hypothyroidism; euthyroidism
Endokrynologia Polska
DOI: 10.5603/EP.a2020.0066
Volume/Tom 72; Number/Numer 1/2021
ISSN 0423–104X, e-ISSN 2299–8306
Introduction
Thyroid disorders (TDs) are common conditions with
potentially devastating health consequences that affect
all populations worldwide. Both hypothyroidism and
hyperthyroidism have their overt, clinically manifested
forms caused by serum abnormities of the thyroid gland
hormones (free thyroxine [FT4] and free triiodothyro-
nine [FT3]). Whereas subclinical forms of TDs show
normal serum levels of free thyroid hormones, there
are inverse feedback changes in thyroid-stimulating
hormone (TSH) levels [1–3].
The prevalence of overt hypothyroidism (OH) in
the general adult population varies between 0–2%
and 5–3% in Europe and between 0–3% and 3–7% in
the USA, depending on the denition used [1]. The
diagnosis of subclinical hypothyroidism (SH) is bio-
chemical, solely based on thyroid function testing. In
iodine-sufcient populations, SH affects up to 10% of
the population [2]. The prevalence of hyperthyroidism
is 0.8% in Europe and 1.3% in the USA [3].
Proper thyroid function is important for the pre-
vention of cardiometabolic diseases. The importance
of thyroid hormones in maintaining cardiovascular
homeostasis can be deduced from clinical and ex-
perimental data showing that even subtle changes in
thyroid hormone concentrations adversely inuence
the cardiovascular system. Some potential mechanisms
Ladislav Štěpánek; Department of Public Health, Faculty of Medicine and Dentistry, Palacký University Olomouc,
Hněvotínská 3, 775 15 Olomouc, Czech Republic, tel: (+42) 608757316; e-mail: ladislav.stepanek@upol.cz
This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles
and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially
9
Endokrynologia Polska 2021; 72 (1)
ORIGINAL PAPER
insulin. None of them had a history of thyroid disorders, and they
were not treated with any drugs known to affect thyroid function.
The study was conducted according to the principles stated in the
Declaration of Helsinki. The study was approved by the Ethics Com-
mittee of University Hospital Olomouc and Faculty of Medicine and
Dentistry, Palacký University Olomouc (Approval No. 20/11). To be
included in the study, all subjects signed informed consent forms.
Laboratory analysis
Venous blood samples were drawn in the morning after a 12-hour
fast. After centrifugation, the serum was used for analyses on the
day of blood collection. Glucose was analysed on a Cobas 8000
(Roche Diagnostics GmbH, Manheim, Germany) using the hexo-
kinase method. Also on the Cobas 8000, TSH, FT4, and FT3 were
measured by electrochemiluminescence immunoassay. Insulin
was determined by chemiluminescent microparticle immunoassay
on Architect i1000SR (Abbott Laboratories, Chicago, IL, USA). All
analyses were performed according to the manufacturer’s instruc-
tions and after verication of methods.
Statistical analysis
Statistical analysis was performed using the computing environ-
ment R (R Foundation for Statistical Computing, Vienna, Austria;
http://www.r-project.org/). All numerical variables were charac-
terised with descriptive statistics. The Wilcoxon signed-rank test
(p-value) was used to compare numerical characteristics between
the given subgroups. Extreme values of variables were found and
excluded using the inner and outer fences method. All variables fol-
lowed normal or near-normal distribution. Correlations of selected
variables were quantied with Pearson’s correlation coefcient (r),
and the level of signicance (p) was determined. Multivariate linear
regression was performed to examine the relationships between
thyroid hormones, age, and sex, as regressors of the dependent
variables insulin and HOMA-IR. Due to a hyperbolic dependence
of IR through the whole spectrum of TDs, evidenced by studies [5],
the correlation and linear regression analyses were performed only
in hypothyroid (both overt and subclinical) and euthyroid subjects.
In other words, IR grows in both hypo- and hyper-thyroidism (in
comparison with normal IR state in euthyroidism), whereas thyroid
parameters change linearly through the whole spectrum. Hyper-
thyroidism was chosen for exclusion because of the expected lower
prevalence in the study population. P-value of less than 0.05 indicates
statistical signicance. The following formula was used to calculates
HOMA-IR (glucose levels in mmol/L, insulin levels in mIU/L) [10]:
HOMA-IR = (glucose × insulin)/22.5
Results
Characteristics of the study population
The basic characteristics of all subjects with respect
to a particular TD are shown in Table 2. Only 23 in-
dividuals from the whole group met the criteria for
hyperthyroidism; therefore, due to the disproportion
to the size of the other subgroups, we did not include
them into the table. As expected, most individuals had
normal thyroid parameters, followed by the OH and
SH subgroups, respectively. Between the subgroups,
differences of the tested parameters, apart from the
thyroid parameters, did not reach statistical signi-
cance. There were no apparent trends of the parameters
between subgroups except for insulin, HOMA-IR, and
linking the two conditions are dyslipidaemia, endo-
thelial dysfunction, blood pressure or body weight
changes, and direct effects of thyroid hormones on the
myocardium [4]. Moreover, thyroid hormones have
an effect on glucose metabolism and probably on the
development of insulin resistance (IR). In hyperthy-
roidism, impaired glucose tolerance may be the result
of mainly hepatic IR, whereas in hypothyroidism the
available data suggest that IR of peripheral tissues
prevails [5]. However, the precise relationship between
TDs, especially subclinical forms, and IR is still under
discussion. IR represents a key pathogenetic mechanism
of cardiometabolic diseases, and its prevention is crucial
in the current dominance of cardiometabolic diseases
in overall mortality [6, 7].
In addition to serum thyroid hormones, some stud-
ies have discussed the relationship between T3/T4 ratio
and various, mostly metabolic, parameters or clinical
outcomes [8, 9]. The T3/T4 ratio is a calculated index used
to indicate thyroid function and the action of hormones
on the tissue. A method for detecting IR that is easy to
use in common clinical practice is the homeostasis model
assessment of IR (HOMA-IR). Its satisfactory correla-
tion with the most accurate glucose clamp techniques
has been conrmed by numerous studies. Even fasting
insulin levels alone reect IR to some extent [10].
The study aimed to investigate the association of
IR with dened TDs and thyroid function parameters,
and through these ndings, identify such thyroid dis-
orders and parameters that are the highest risk for the
development of IR.
Material and methods
Study population
The study comprised 1425 middle-aged individuals (317 males, 1108
females) examined in a co-author’s internal medicine outpatient
centre in Hradec Králové, Czech Republic. Data were collected in
2009–2016 from the patients’ rst visits to the centre. The labora-
tory analyses below, including standard 75 g oral glucose tolerance
test (OGTT), were performed, and, at the same time, their basic
anthropometric parameters (waist circumference [WC], weight, and
height) were measured. The obtained data were used to calculate
body mass index (BMI) and HOMA-IR for each participant. Based
on their TSH and FT4 levels and the manufacturer ’s instructions,
all subjects were divided into subgroups according to Table 1. None
of the included subjects was treated with oral antidiabetic drugs or
Table 1. Study subgroups according to thyroid hormone levels
Subgroups/thyroid status TSH [mIU/L] FT4 [pmol/L]
Euthyroidism 0.4–4.0 and 9–23
Subclinical hypothyroidism > 4.0 and 9–23
Overt hypothyroidism > 4.0 and < 9
Hyperthyroidism < 0.4 or > 23
TSH — thyroid-stimulating hormone; FT4 — free thyroxine
10
ORIGINAL PAPER
Thyroid disorders and insulin resistance Ladislav Štěpánek et al.
two-hour glucose levels, which showed steady growth
from euthyroidism through SH to OH.
Correlation analysis
The highest correlation coefcients of thyroid param-
eters were noted with insulin levels and HOMA-IR as
seen from Table 3, namely correlations of insulin with
the FT3/FT4 ratio (r = 0.206) and FT3 (r = 0.205), re-
spectively. Although the correlations were weak, they
reached high statistical signicance (p < 0.001). There
were also highly signicant correlations of both FT3
and the FT3/FT4 ratio with HOMA-IR (r = 0.181 and
r = 0.165, respectively). Figure 1 depicting the correla-
tions of the FT3/FT4 ratio suggests no difference be-
Table 2. Basic characteristics in study subgroups — mean value (95% condence interval of the mean value)
Characteristics Euthyroidism p value Subclinical
hypothyroidism p value Overt hypothyroidism
N (males, females) 1036
(243, 793) 76
(11, 65) 290
(57, 233)
Age [yrs] 42.21
(41.61; 42.81) 0.397 43.94
(43.21; 44.67) 0.452 43.23
(42.72; 43.75)
BMI [kg/m²] 31.17
(29.64; 32.79) 0.204 32.98
(25.66; 42.40) 0.172 32.04
(30.19; 34.00)
Waist circumference [cm] 109.69 (107.28;
112.10) 0.656 108.22
(102.01; 114.43) 0.899 110.78
(108.78; 112.78)
Glucose [mmol/L] 5.62
(5.58; 5.66) 0.223 5.73
(5.56; 5.90) 0.372 5.63
(5.56; 5.70)
Insulin [mIU/L] 6.70
(6.42; 6.98) 0.35 7.12
(5.93; 8.55) 0.483 7.85
(7.26; 8.48)
2-hour OGTT 6.26
(6.16; 6.35) 0.973 6.27
(5.87; 6.71) 0.097 6.60
(6.42; 6.80)
HOMA-IR 1.68
(1.60; 1.75) 0.224 1.82
(1.50; 2.21) 0.804 1.96
(1.80; 2.13)
TSH [mIU/L] 1.91
(1.86; 1.96) < 0.001 5.32
(5.04; 5.61) 0.091 6.44
(2.58; 4.31)
FT4 [pmol/L] 10.81
(10.73; 10.90) 0.373 10.68
(10.37; 10.99) < 0.001 8.28
(8.20; 8.36)
FT3 [pmol/L] 5.21
(5.17; 5.26) 0.711 5.18
(5.00; 5.37) 0.876 5.13
(5.05; 5.22)
FT3/FT4 ratio 0.48
(0.48; 0.49) 0.557 0.48
(0.46; 0.51) < 0.001 0.62 (0.61; 0.63)
BMI — body mass index; OGTT — oral glucose tolerance test; HOMA-IR — homeostasis model assessment of insulin resistance; TSH — thyroid-stimulating hormone;
FT4 — free thyroxine; FT3 — free triiodothyronine
Table 3. Pearson’s correlation coefcients (r) of thyroid function parameters
Characteristics TSH FT4 FT3 FT3/FT4
BMI 0.008 0.035 –0.055 –0.068*
Waist circumference 0.002 0.033 0.001 0.038
Glucose 0.014 0.064* 0.018 –0.029
Insulin –0.015 –0.081* 0.205** 0.206**
2-hour OGTT 0.007 –0.026 –0.007 0.044
HOMA-IR –0.015 –0.050 0.181** 0.165**
*p < 0.05, **p < 0.001; TSH — thyroid-stimulating hormone; FT4 — free thyroxine; FT3 — free triiodothyronine; BMI — body mass index; OGTT — oral glucose
tolerance test; HOMA-IR — homeostasis model assessment of insulin resistance
11
Endokrynologia Polska 2021; 72 (1)
ORIGINAL PAPER
tween males and females. As for the parameters not as-
sociated with thyroid functions, there were statistically
highly signicant correlations of WC and body weight
with both insulin and HOMA-IR, the strongest being
correlated body weight with HOMA-IR (r = 0.494).
Regression analysis
The impact of individual IR predictors is expressed with
multivariate linear regression models that use linear
coefcients to show the effects of one-point increases
of these predictors (independent variables) on the de-
pendent variables, HOMA-IR and insulin, respectively
(Tab. 4). Except for the sex and age, the FT3/FT4 ratio
was the only statistically signicant predictor of both
HOMA-IR and insulin. If the ratio increases by one
point, HOMA-IR and insulin will increase by a mean of
5.26 (p = 0.027) and 18.01 (p = 0.023), respectively. With
each year of age, HOMA-IR and insulin will increase by
a mean of 0.02 (p < 0.001) and 0.04 (p = 0.25), respec-
tively. Female sex was a signicant predictor of a lower
insulin level and HOMA-IR in our study population.
Discussion
The obtained results of the correlation analysis revealed
only a few statistically signicant and very weak asso-
ciations. The regression analysis conrmed a signicant
relationship only between IR and the FT3/FT4 ratio. The
Table 4. Effects of every 1-point increase of independent variables on the dependent variables HOMA-IR and insulin
Independent
variables
Linear coefcient Standard error t-value p-value
HOMA-IR Insulin HOMA-IR Insulin HOMA-IR Insulin HOMA-IR Insulin
Intercept –2.45 –5.82 1.33 4.44 –1.85 –1.31 0.065 0.19
Age 0.02 0.04 < 0.01 0.02 3.97 2.25 < 0.001 0.025
Sex (female) –0.8 –2.31 0.14 0.47 –5.75 –4.96 < 0.001 < 0.001
TSH –0.01 –0.05 0.02 0.05 –0.75 –0.96 0.455 0.338
FT4 0.16 0.44 0.12 0.39 1.39 1.12 0.166 0.261
FT3 0.04 0.23 0.25 0.84 0.17 0.27 0.862 0.785
FT3/FT4 ratio 5.26 18.01 2.37 7.92 2.22 2.27 0.027 0.023
HOMA-IR — homeostasis model assessment of insulin resistance; TSH — thyroid-stimulating hormone; FT4 — free thyroxine; FT3 — free triiodothyronine
Figure 1. Scatter diagrams showing correlations of free triiodothyronine/free thyroxine (FT3/FT4) ratio with fasting insulin levels (A)
and HOMA-IR (B) with 95% condence bands for the medians of variables on the y-axis for a given variable on the x-axis. There are
no obvious sex differences in the relationship of the ratio and insulin resistance
50
40
30
20
10
0
15
10
5
0
Insulin [mIU/L]
HOMA-IR
FT3/FT4 ratio FT3/FT4 ratio
0.4 0.6 0.8 1.0 1.2 0.4 0.6 0.8 1.0 1.2
Female Male
12
ORIGINAL PAPER
Thyroid disorders and insulin resistance Ladislav Štěpánek et al.
results also demonstrate both HOMA-IR and insulin
levels increasing in the way from euthyroidism through
SH to OH, although without statistical signicance.
Epidemiological evidence indicates that both OH and
SH are connected with IR. Some studies showed a sta-
tistically signicant increase of HOMA-IR and insulin
levels in subjects with SH compared to the euthyroid
[11, 12]. However, some ndings showed no or insigni-
cant difference between SH and the euthyroid state [13,
14]. A study by Wang et al. also recorded an increase in
HOMA-IR between SH and OH, as was the case in our
study, although in our case without reaching statistical
signicance [12]. Comparable IR between SH and OH
subjects was noted in a study by Maratou et al. [15]. We
also demonstrate an increase of two-hour OGTT values
in SH and OH compared to euthyroidism.
According to the population prevalence of TDs
indicated in the introduction, hypothyroidism pre-
dominates. SH was estimated to affect up to 10%, with
the highest prevalence among women and elderly
individuals. However, SH frequently reverts to euthy-
roidism, and TSH levels rise as people without TDs
age, making it likely that the prevalence of SH may be
overestimated [2]. The occurrence of TDs in our study
sample does not exactly correspond to the proposed
population prevalence. However, the study did not
comprise a random adult population, but rather pa-
tients of a stated outpatient centre.
The most common cause of hypothyroidism in
iodine-sufcient populations is Hashimoto’s thyroiditis
(HT). A chronic inammation resulting from an imbal-
ance between pro-inammatory and anti-inammatory
cytokines in HT might be responsible for IR in hypothy-
roidism. Subjects with highly positive thyroid peroxi-
dase antibodies (TPOabs) had elevated fasting insulin
levels compared to those with lower titers of TPOabs, in
a study by Mazarehi et al. [16]. OH was associated with
obesity, promoting the production of pro-inammatory
cytokines and contributing to the development of IR.
Moreover, BMI was positively correlated with TPOabs
in men, suggesting that the pathogenesis of IR in hy-
pothyroidism is a complex and interrelated process [17,
18]. In the present study, subjects with both SH and OH
showed higher BMI values compared to euthyroidism.
Elevated levels of the FT3/FT4 ratio were associated
with metabolic syndrome and some of its components
such as obesity, elevated triglycerides, fasting blood
glucose levels, and lower high-density lipoprotein
cholesterol levels in euthyroid subjects [19, 20]. Based
on regression analysis in a sample of 132,346 adults,
Park et al. conrmed the FT3/FT4 ratio to have a better
predictive power for metabolic syndrome than TSH
[21]. In hypothyroidism and euthyroidism, as TSH
levels rise the FT3/FT4 ratio also rises. Levothyroxine
therapy was proved to decrease the FT3/FT4 ratio [22,
23]. Given the association of both hypothyroidism and
the FT3/FT4 ratio with IR, thyroxine supplementation
in indicated cases may help not only in achieving eu-
thyroidism but also in improving IR.
The study has certain limitations. We considered all
hypothyroid subjects as having a peripheral form (not
distinguishing between central and peripheral forms)
of hypothyroidism. However, due to the low prevalence
of central hypothyroidism, there should be no major
bias for this reason.
Conclusion
Both SH and OH are associated with increased
HOMA-IR, fasting insulin levels, and two-hour OGTT
glucose levels compared to euthyroidism. From the
common laboratory parameters of the thyroid gland,
the FT3/FT4 ratio shows the strongest relationship to IR.
The FT3/FT4 ratio should be more emphasised in the di-
agnosis and treatment of TDs. After further verication,
pharmacological lowering of the ratio could be a pos-
sible targeted way to reverse the development of IR.
The results are valid for middle-aged European adults.
Conict of onterest
Nothing to declare.
Funding
The study was supported by the grant IGA_LF_UPOL
2020_031.
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... In NHANES participants, patients treated with LT4 experienced a 15-20% reduction in circulating T3/T4 ratios and normalizing serum TSH, with 15% of patients unable to achieve normal serum T3 levels 27 . Studies have also shown that pharmacologically reducing the T3/T4 ratio can decrease insulin resistance 28 . ...
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In light of research indicating that normal TSH levels do not necessarily reflect clinical euthyroidism in hypothyroid patients, and given the patient dissatisfaction with levothyroxine (LT4) monotherapy, we evaluate the response to weight loss treatment in patients with obesity and primary hypothyroidism who are euthyroid under LT4 therapy, with a focus on weight and metabolic parameters. The retrospective study included 138 subjects with obesity (BMI ≥ 30 kg/m²), 69 women with hypothyroidism on levothyroxine, and 69 age- and BMI-matched women without thyroid disease. Secondary causes of obesity, medications that may affect thyroid functions and metabolic parameters, chronic and oncological disease, pregnancy, TSH outside the reference range, follow-up periods of less than one year, and bariatric surgery were the exclusion criteria. Patients’ characteristics and metabolic responses to weight reduction treatment consisting of calorie restriction, moderate exercise, and metformin if needed were evaluated. TSH and fT4 levels were higher, and fT3 and T3/T4 ratios were lower all within the reference ranges in hypothyroid women. They were less insulin resistant. Both patient’ groups experienced a significant decrease in body weight, BMI, and atherogenic index of plasma (AIP) during the follow-up (p = 0.001). Insulin resistance was not changed. The groups’ body weight, BMI, HOMA-IR, and AIP changes were similar at the end of the study (p = 0.876, p = 0.850, p = 0.555, p = 0.293). The results suggest that achieving euthyroid status via levothyroxine monotherapy in hypothyroid women leads to weight loss responses comparable to those in women with normal thyroid. This supports the effectiveness of current hypothyroidism treatment strategies, emphasizing TSH level normalization, in achieving clinical euthyroidism concerning weight loss outcomes.
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Objective There has been some confusion in earlier research on the connection between thyroid function and polycystic ovary syndrome (PCOS). This research is aimed to probe into the correlation between thyroid condition and the risk of PCOS from a new standpoint of thyroid hormone sensitivity. Methods This research comprised 415 females with PCOS from Drum Tower Hospital Affiliated with the Medical School of Nanjing University, and 137 non-PCOS individuals were selected as the normal control. Based on free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH), we calculated the thyroid hormone sensitivity indices, which consist of Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), Thyrotroph Thyroxine Resistance Index (TT4RI) and Free Triiodothyronine /Free thyroxine (FT3/FT4). The binary logistic regression model was adopted to investigate the correlation between thyroid hormone sensitivity indices with the risk of PCOS. Pearson or Spearman correlation analysis was employed to explore the association among thyroid-related measures with metabolic parameters in PCOS. Results Results of this research showed that females with PCOS had rising TFQI, TSHI, TT4RI, and FT3/FT4 levels compared with the control group. After adjustment for the impact of various covariates, there was no significant correlation between FT3/FT4 and the risk of PCOS; However, the odds ratio of the third and fourth vs. the first quartile of TFQI were 3.57(95% confidence interval [CI]:1.08,11.87) and 4.90(95% CI:1.38,17.38) respectively; The odds ratio of the fourth vs. the first quartile of TSHI was 5.35(95% CI:1.48,19.37); The odds ratio of the second vs. the first quartile of TT4RI was 0.27(95%CI 0.09,0.82). In addition, no significant correlation was observed between thyroid-related measures and metabolic measures in females with PCOS. Conclusions A reduction in the sensitivity of central thyroid hormone is closely correlated with a higher risk of PCOS. Further research is necessary to corroborate our findings and the supporting mechanisms.
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Objectives A connection between thyroid hormones (THs) and diverse metabolic pathways has been reported. We evaluated thyroid function and tissue sensitivity to THs in children and adolescents with T1D in comparison to euthyroid controls. Additionally, we investigate whether a relationship exists between sensitivity indices and metabolic parameters. Methods A retrospective analysis was conducted on 80 pediatric patients diagnosed with T1D. Clinical parameters, TSH, FT3, FT4, and the presence of MS were documented. Additionally, indices of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were assessed. Thirty healthy subjects were considered as controls. Results The overall prevalence of MS was 7.27 %, with MS identified in 8 out of 80 (10 %) T1D subjects; none of the controls manifested MS (p<0.01). No significant differences were observed in indexes of tissue sensitivity to THs between subjects with or without MS (all p>0.05). Correlations between THs and indexes of THs tissue sensitivity and metabolic parameters in controls and T1D patients were noted. Conclusions This study affirms a heightened prevalence of MS in children with T1D compared to controls and underscores the potential role of THs in maintaining metabolic equilibrium.
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Obesity is a chronic, relapsing, and progressive disease that leads to negative health consequences. Excessive adiposity frequently coexists with metabolic and nonmetabolic complications, deteriorating health and reducing quality of life and life span. Individuals with obesity are not a homogenous group and can present different obesity phenotypes. The most common obesity phenotypes include: metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). The latter category involves those with developed metabolic syndrome (MetS) and non-fully-developed metabolic syndrome (pre-MetS). The fundamental factor leading to obesity is imbalance between energy uptake and expenditure. From this perspective the thyroid gland plays the pivotal role in metabolism regulation and obesity development. The thyroid regulates thermogenesis, appetite, and lipids turnover. Clinically, hypothyroid patients have decreased metabolic rate and subsequently experience increase of BMI and excess adiposity. The interaction between the thyroid gland and obesity is bidirectional. Several mechanisms of alteration of the hypothalamus-pituitary-thyroid axis in obesity are proposed. Excessive adiposity and dysfunction of adipose tissue may contribute to the development of thyroid functional and structural impairment, such as autoimmunity, thyroid nodules, and thyroid cancer. The prevalence of certain thyroid disorders in obese individuals is higher than in nonobese subjects and this trend is more pronounced in unhealthy obesity phenotypes. The aim of this mini-review is to present the current knowledge on the interaction between thyroid gland disorders and obesity, with special focus on obesity phenotypes.
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Introduction. Hypothyroidism is a common endocrine disorder that affects millions of people worldwide. The diagnosis and monitoring of this condition often rely on thyroid hormone levels, which can be limited in their accuracy. Pentraxin 3 (PTX3) is a protein family that is involved in the innate immune response and is distinguished by its distinct pentameric structure. Aim. To evaluate the utility of serum PTX3 levels in detecting and monitoring hypothyroidism. Materials and Methods . A case-control design of the study included 90 participants between the ages of 20 and 50 years. These participants were divided into three groups: overt hypothyroidism (OH), subclinical hypothyroidism (SCH), and a control group of healthy individuals. Anthropometric data, including age, sex, weight, height, body mass index (BMI), and hormonal parameters were measured and recorded for each participant. Results. Our work demonstrates that serum PTX3 levels were significantly elevated in individuals with hypothyroidism, compared to those with normal thyroid function (p<0.001). Furthermore, PTX3 levels correlated positively with TSH levels (r=0.62, p<0.001) and negatively with T4 levels (r= -0.53, p<0.001). Conclusion. The findings suggest that serum PTX3 levels can be a useful biomarker for detecting and monitoring hypothyroidism, particularly in cases of SCH. The study’s exclusion criteria made sure that no other systemic illnesses or medication use could have tainted the findings. Therefore, the use of plasma PTX3 levels in hypothyroidism detection and monitoring may prove to be a valuable clinical tool in the future.
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Objective: This study aims to explore the correlation between the free-triiodothyronine (FT3)-to-free-thyroxine (FT4) ratio (FT3/FT4) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: This study retrospectively analyzed 1729 patients with T2DM hospitalized in the Department of Endocrinology, Peking University International Hospital, from January 2017 to August 2021, including 1075 males and 654 females. In accordance with the FT3/FT4, the patients were divided into three groups. Results: (1) The levels of glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and postprandial blood glucose (PBG) among the three groups were significantly different, with the low FT3/FT4 group having the highest HbA1c, FBG and PBG among the three groups (F = 39.39, p < 0.01; F = 27.04, p < 0.01; F = 5.76, p = 0.03; respectively). (2) The proportion of DKD is the highest in the low FT3/FT4 group and the lowest in the high FT3/FT4 group (χ2 = 25.83, p < 0.01). (3) Logistic regression showed that low FT3/FT4 were independent risk factors for DKD (OR = 2.36, 95 CI% 1.63, 3.43; p = 0.01). Conclusion: A decrease in the FT3/FT4 is an independent predictor of DKD occurrence in patients with T2DM.
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Objective Accumulating evidence has suggested that thyroid hormone levels affect the prognosis of acute ischemic stroke (AIS), but the results have been inconsistent. Methods Basic data, neural scale scores, thyroid hormone levels, and other laboratory examination data of AIS patients were collected. The patients were divided into excellent and poor prognosis group at discharge and 90 days after discharge. Logistic regression models were applied to evaluate the relationship between thyroid hormone levels and prognosis. A subgroup analysis was performed based on stroke severity. Results A number of 441 AIS patients were included in this study. Those in the poor prognosis group were older, with higher blood sugar levels, higher free thyroxine (FT4) levels, and severe stroke (all p < 0.05) at baseline. Free thyroxine (FT4) showed a predictive value (all p < 0.05) for prognosis in the model adjusted for age, gender, systolic pressure, and glucose level. However, after adjustment for types and severity of stroke, FT4 showed insignificant associations. In the severe subgroup at discharge, the change in FT4 was statistically significant (p = 0.015), odds ratio (95% confidence interval) = 1.394 (1.068–1.820) but not in the other subgroups. Conclusions High-normal FT4 serum levels in patients with severe stroke receiving conservative medical treatment at admission may indicate a worse short-term prognosis.
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Introduction Thyroid hormones play major roles in the regulation of body composition and metabolism, and therefore, the relationship between thyroid hormones and cardio-metabolic risk has been extensively studied in adults. In this study, we aimed to test whether free triiodothyronine (fT3) associates longitudinally with cardio-metabolic risk factors in euthyroid children. Methods A prospective study cohort of 599 apparently healthy school-age children were assessed at baseline (mean age 8.1 ± 2.1 years), of whom 270 children were also assessed at follow-up (4 years later). Circulating thyroid-stimulating hormone (TSH), free thyroxine (fT4), and fT3 were measured, and cardio-metabolic risk was assessed by means of body mass index (BMI), waist circumference, visceral fat (by ultrasound), blood pressure, circulating lipids, and homeostasis model assessment of insulin resistance (HOMA-IR) index, both at baseline and at follow-up. Results All studied children had normal thyroid function tests. Independent associations between baseline fT3 and both baseline and follow-up BMI, systolic blood pressure, mean arterial blood pressure, triglycerides, and HOMA-IR were found using multivariate regression analysis (adjusting for sex and baseline age and BMI). Analyses of effect sizes showed that for each 1 unit-increase in baseline fT3 (pg/ml), follow-up BMI–standard deviation score (SDS) increased by 0.31 units (z-score) and systolic blood pressure by 6.6 units (mmHg). The observed longitudinal associations were more robust in children belonging to the upper TSH tertile who showed higher TSH levels and were characterized by weighing more and having the highest fT3 levels. In these children, for each 1 unit-increase in baseline fT3 (pg/ml), follow-up BMI-SDS increased by 0.67 units (z-score) and systolic blood pressure by 10.2 units (mmHg). Conclusions Circulating fT3 associates longitudinally with cardio-metabolic risk factors in euthyroid children with higher TSH. The observed associations of thyroid hormones in these children could conceivably respond to a homeostatic attempt to reduce their cardio-metabolic risk.
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Objective The aim of this study was to elaborate the link of thyroid hormones (THs) and metabolic syndrome (MetS) in a Chinese euthyroid employee population with MetS component(s). Methods An annual health checkup was performed on employees in 2019. Anthropometric parameters, metabolic parameters, and thyroid function were measured. A questionnaire was used in conjunction with Zhenhai Lianhua Hospital database to receive employees' medication records and thyroid surgical history records. Results A total of 5486 eligible employees were included; the prevalence of MetS was generally higher in males than in females (38.9 vs. 30.4%, P < 0.001). Among employees with central obesity, hypertriglyceridemia, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), the prevalence of MetS was 68.8, 63.6, 68.2, 48.8, and 60.0% in males and 72.6, 63.3, 61.3, 42.3, and 42.3% in females, respectively. Logistic regression analysis showed that thyroid-stimulating hormone and free thyroxine (FT4) quartiles had no significant impact on MetS. Free triiodothyronine/free thyroxine (FT3/FT4) and free triiodothyronine (FT3)) quartiles were positively associated with the increased odds ratio (OR) for MetS and dyslipidemia (hypertriglyceridemia and low HDL-C), regardless of gender. In males, FT3 and FT3/FT4 quartiles were positively associated with the OR for central obesity, whereas FT4 quartiles were negatively associated; both FT3 and FT4 quartiles were positively associated with increased OR of hyperglycemia, while similar results were not observed in females. Interaction analysis indicated no significant effect of gender and TH interactions on risk of MetS. Conclusion High FT3 and FT3/FT4 were strongly linked with MetS and dyslipidemia in our study, even in the euthyroid individuals. Tighter control of thyroid function was necessary for those with preexisting MetS component(s).
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Context It is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist and what is the role of combination therapy with LT4 and liothyronine (LT3), are questions that remain unclear. Here we explore evidence of abnormal thyroid hormone (TH) metabolism in LT4-treated patients, and offer a rationale for why some patients perceive LT4 therapy as a failure. Evidence Acquisition The review is based on a collection of primary and review literature gathered from a PubMed search of hypothyroidism, levothyroxine, liothyronine, and desiccated thyroid extract, among other keywords. PubMed searches were supplemented by Google Scholar and the authors’ prior knowledge of the subject. Evidence Synthesis In most LT4-treated patients, normalization of serum TSH levels results in decreased serum T3/T4 ratio, with relatively lower serum T3 levels; in at least 15% of the cases, serum T3 levels are below normal. These changes can lead to a reduction in TH action, which would explain the slower rate of metabolism and elevated serum cholesterol levels. A small percentage of patients might also experience persistent symptoms of hypothyroidism, with impaired cognition and tiredness. We propose that such patients carry a key clinical factor, e.g. specific genetic and/or immunologic makeup, that is well compensated while the thyroid function is normal but might become apparent when compounded with relatively lower serum T3 levels. Conclusions After excluding other explanations, physicians should openly discuss and consider therapy with LT4 and LT3 with those hypothyroid patients that have persistent symptoms or metabolic abnormalities despite normalization of serum TSH level. New clinical trials focused on symptomatic patients, genetic makeup and comorbidities, with the statistical power to identify differences between monotherapy and combination therapy, are needed.
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Background: In recent years, the relationship between thyroid stimulating hormone (TSH) and obesity has been widely discussed. However, it is unclear how thyroid hormone concentrations relate to body weight and its impact on metabolic risk markers. This study aimed to assess how thyroid function is linked to underweight, overweight, or obesity, and metabolic risk markers in adults. Methods: A total of 16,975 subjects, aged 18-80 years, who attended the Health Management Center of Tongji Hospital, Wuhan, China were enrolled in this study. Anthropometric and laboratory data were collected and analyzed. Results: Serum free triiodothyronine (fT3) and fT3/free thyroxine (fT4) ratio (fT3/fT4) were positively associated with body mass index (BMI) (P < 0.001), while there was a negative relationship between fT4 and BMI (P < 0.001) according to multivariable regression analysis adjusted for age and sex. Associations between thyroid hormone concentrations and markers of blood pressure, and lipid and glucose metabolism were identified after adjustment for age, sex, and BMI, with TSH being negatively associated with fasting blood glucose (FBG). fT3 was positively associated with systolic blood pressure and low-density lipoprotein-cholesterol, while fT4 was positively associated with diastolic blood pressure, FBG, and high-density lipoprotein-cholesterol (HDL-C), and negatively associated with hemoglobin A1c (HbA1c) and triglyceride. Finally, fT3/fT4 was positively associated with HbA1c and triglyceride, and negatively associated with HDL-C. Conclusions: Overweight or obese participants had a high serum concentration of fT3, high fT3/fT4 ratio, and a low concentration of fT4. Underweight participants had high concentrations of fT4 and low concentrations of fT3. Thus, relationships between thyroid hormones and metabolic risk markers were identified which suggest that thyroid function might be one factor that influences body weight and the co-morbidities of obesity.
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There is an intensive link between obesity and thyroid dysfunction, but this relationship in Asians is still unclear. This study was conducted to define the impact of obesity on risk of hypothyroidism and thyroid autoimmunity among Chinese adults. A population-based, cross-sectional study was carried out, which enrolled a total of 2,808 Chinese adults. To assess the associations of obesity with hypothyroidism and thyroid autoimmunity, odds ratio (ORs) with 95% confidence intervals (95%CIs) were calculated through logistic regression model, and the correlations of body mass index (BMI) with TPOAb and TGAb were also analyzed. Obese females had higher risk of hypothyroidism (22.7 vs. 15.0%; OR = 1.66, 95%CI 1.10–2.53; P = 0.02) and higher risk of subclinical hypothyroidism (22.1 vs. 13.4%; OR = 1.83, 95%CI 1.20–2.80; P = 0.005) than non-obese females. Multivariate logistic regression analysis found significant associations of obesity with hypothyroidism (Adjusted OR = 1.54, 95%CI 1.00–2.38; P = 0.05) and subclinical hypothyroidism (Adjusted OR = 1.69, 95%CI 1.09–2.63; P = 0.02) in females after adjustment for confounding factors. No association between obesity and hypothyroidism was observed in male participants. Spearman's correlation analysis suggested BMI was significantly and positively correlated with TPOAb (Spearman's r = 0.062, P = 0.022) in men but not in women. Linear regression analysis suggested an obviously positive correlation of BMI with TPOAb in men (β = 0.018, P = 0.015) and an obviously negative correlation of BMI with TGAb in women (β = −0.025, P = 0.012), respectively. The study suggests sex differences in the associations of obesity with hypothyroidism and thyroid autoimmunity among Chinese adults. Further studies are needed to better understand the exact mechanism of sex difference in the obesity-thyroid relationship.
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Background: Subclinical hypothyroidism known as mild thyroid disorder without significant sign and symptoms. The correlation between subclinical hypothyroidism and some of cardiovascular disease risk factors such as serum lipids, homocysteine levels and also insulin resistance index is not well established and the current study was conducted to clarify this issue. Methods and materials: Seventy four patients with mild elevation in levels of thyroid stimulating hormone (TSH) along with normal levels of T3 and T4 were selected as patients group and 74 age and sex matched individuals were selected as healthy control group. Serum insulin, triglyceride, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and homocysteine levels were measured. Obtained data compared between groups with independent sample t-test. For evaluation of the correlation between mentioned parameters Pearson correlation coefficient method was used. Results: Serum levels of LDL-C and total cholesterol significantly increased in SCH group compared to healthy control group. Homeostatic Model Assessment of Insulin Resistance (HOM-IR) and serum homocysteine level significantly elevated in patients with SCH compared to control group. There was a significant direct correlation between HOM-IR and serum homocysteine levels in SCH patients. Conclusion: Subclinical hypothyroidism likely have significant effect on insulin resistance as major diabetes risk factors and also cardiovascular disease risk factors such as homocysteine. The direct correlation between HOM-IR with serum homocysteine level indicate the possible role of insulin resistance in elevation of serum homocysteine in SCH patient group.
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The interest in the relationship between thyroid dysfunction and obesity is on the increase. This study compares the triiodothyronine-to-thyroxine (T3/T4) ratio in obese and lean children and adolescents, and correlates thyroid hormones with body mass index (BMI) in obese Nigerian children. It is a retrospective study of records of 76 obese children and adolescents with a BMI of 31.7 ± 0.1 kg/m2 (26 males aged 10.9 ± 0.35 years, and 50 females aged 10.8 ± 0.4 years) that were referred to the laboratory for thyroid hormone evaluation because of their obese status. The controls were 20 age-matched non-obese apparently healthy subjects, with a mean age of 11.0 ± 0.47 years and a BMI of 20.2 ± 0.2 kg/m2. Serum T3, T4, and thyroid stimulating hormone (TSH) were determined using ELECSYS 1010 auto-analyzer (Roche Diagnostics, Penzberg, Germany). The BMI (p < 0.001), T3 (p < 0.01), TSH (p < 0.001) and T3/T4 ratio (p < 0.001) were significantly higher in obese than non-obese children and adolescents. Triiodothyronine (r = 0.230; p < 0.05), TSH (r = 0.272; p < 0.02), and T3/T4 ratio (r = 0.232; p < 0.05) correlated positively with BMI in obese children and adolescents. The T3/T4 ratio (p < 0.005) was significantly higher in obese boys than obese girls. Serum T3, TSH, and T3/T4 ratio correlated positive with BMI in obese Nigerian children and adolescents. Since thyroid dysfunction represents a continuum from asymptomatic to clinical symptomatic disease, it is suggested that obese children be counseled on the need to maintain ideal BMI in order to avoid the risks associated with obesity.
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Aims To determine the association between free triiodothyronine (FT3), free thyroxine (FT4) and free-triiodothyronine-to-free-thyroxine ratio (FT3/FT4) levels and Metabolic Syndrome (MetS). Materials and methods We carried out an analytical cross-sectional study in euthyroid adults of both sexes, who attended the outpatient service of a private clinic in Lima-Peru during the 2014–2016 period. Participants were divided into tertiles (low, intermediate and high) according to their FT3, FT4, and FT3/FT4 ratio values. MetS was defined when three or more metabolic criteria were met by the participants. ROC curves were constructed, and Youden’s Index were used to identify the optimal cut-points of each thyroid marker. We elaborated crude/adjusted Poisson regression models to evaluate the association between the thyroid markers and the presence of MetS. The reported association measure was the prevalence ratio (PR) with their respective 95% confidence intervals (95% CI). Results We analyzed 245 participants, the average age was 38.5±10.3years, 29.8% were males, and the prevalence of MetS was 31%. In the adjusted Poisson regression models, the prevalence of MetS was higher among the high FT3 tertile compared to the low tertile (aPR=2.01; 95% CI: 1.22–3.34). The prevalence of MetS was higher among the intermediate FT3/FT4 ratio tertile and the high FT3/FT4 ratio tertile compared to the low tertile, (aPR=1.78; 95% CI: 1.02–3.10) and (aPR=2.80; 95% CI: 1.67–4.72); respectively. The highest areas under the curve (AUC) were found for FT3 and FT3/FT4 ratio with areas of 0.654 (95% CI: 0.58–0.73) and 0.649 (95% CI: 0.57–0.72); respectively. Conclusion Elevated levels of FT3 and FT3/FT4 ratio were associated with MetS in a euthyroid population
Article
Background Free triiodothyronine (FT3)/free thyroxine (FT4) ratio is an index estimating the peripheral activity of thyroid hormones. In a previous experience, we identified a prognostic role for FT3/FT4 ratio in chemorefractory patients treated with regorafenib. Therefore, we planned this post hoc analysis of the phase III CORRECT trial of regorafenib versus placebo. Methods Seven hundred fifty-eight out of 760 randomised patients (503 in the regorafenib and 255 in the placebo arm) were evaluable for the present analyses, based on availability of FT3 and FT4 baseline values. Co-primary objectives were to explore the predictive role of FT3/FT4 ratio in patients treated with regorafenib compared with placebo and to validate the prognostic value of FT3/FT4 ratio in the CORRECT trial. Results For patients randomised to regorafenib, median overall survival (OS) was 4.0, 7.5 and 9.8 months in low, intermediate and high FT3/FT4 ratio subgroups, respectively. Hazard ratio (HR) for OS was 0.40 (p < 0.0001) when comparing intermediate versus low and 0.32 (p < 0.0001) when comparing high versus low FT3/FT4 ratio. In the placebo arm, median OS was 3.3, 5.6 and 7.7 months, in the three subgroups. HR for OS was 0.47 (p < 0.0001) when comparing intermediate versus low and 0.33 (p < 0.0001) when comparing high versus low. FT3/FT4 ratio retained its association with OS in the multivariate model in both arms. Conclusions While rejecting the predictive effect of baseline FT3/FT4 ratio, present data strengthen the prognostic role of the ratio, pave the way for direct clinical application, underline the need for a better biological understanding and suggest possible therapeutic implications for thyroid hormones.
Article
Importance Subclinical hypothyroidism, defined as an elevated serum thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) level with normal levels of free thyroxine (FT4) affects up to 10% of the adult population. Observations Subclinical hypothyroidism is most often caused by autoimmune (Hashimoto) thyroiditis. However, serum thyrotropin levels rise as people without thyroid disease age; serum thyrotropin concentrations may surpass the upper limit of the traditional reference range of 4 to 5 mU/L among elderly patients. This phenomenon has likely led to an overestimation of the true prevalence of subclinical hypothyroidism in persons older than 70 years. In patients who have circulating thyroid peroxidase antibodies, there is a greater risk of progression from subclinical to overt hypothyroidism. Subclinical hypothyroidism may be associated with an increased risk of heart failure, coronary artery disease events, and mortality from coronary heart disease. In addition, middle-aged patients with subclinical hypothyroidism may have cognitive impairment, nonspecific symptoms such as fatigue, and altered mood. In the absence of large randomized trials showing benefit from levothyroxine therapy, the rationale for treatment is based on the potential for decreasing the risk of adverse cardiovascular events and the possibility of preventing progression to overt hypothyroidism. However, levothyroxine therapy may be associated with iatrogenic thyrotoxicosis, especially in elderly patients, and there is no evidence that it is beneficial in persons aged 65 years or older. Conclusions and Relevance Subclinical hypothyroidism is common and most individuals can be observed without treatment. Treatment might be indicated for patients with subclinical hypothyroidism and serum thyrotropin levels of 10 mU/L or higher or for young and middle-aged individuals with subclinical hypothyroidism and symptoms consistent with mild hypothyroidism.
Article
In euthyroidism, as thyroid Stimulating hormone (TSH) levels increase, the free triiodothyronine (FT3) to free thyroxine (FT4) ratio increases. The aim of this study was to assess if beyond the euthyroid range of TSH levels FT3/FT4 ratio continues to increase and if levothyroxine treatment reduces this ratio, possibly through TSH suppression. This cross sectional retrospective study included a total of 77 832 patients [age 22.76±15.17 years (4 days to 112 years)] evaluated and treated in community clinics between January 2009 and September 2013. Blood samples drawn in community clinics for which TSH, FT4, FT3, age, and gender were available were included. Tests with TSH below 0.5 IU/l were excluded as were samples taken during pregnancy. The FT3/FT4 ratio continued to increase significantly even with TSH above 50 mIU/l (p for trend<0.001) with an increase of more than 50% over the entire TSH range. With increasing age and female gender, the phenomenon was less prominent (p<0.001). Levothyroxine treated patients had significantly lower FT3/FT4 ratios in comparison to untreated patients up to TSH levels of 5.0 mIU/l. In conclusion, increasing TSH increases FT3/FT4 ratio even with severe hypothyroidism, less so with aging. With levothyroxine therapy, a ratio similar to untreated patients is achieved at TSH of above 5.0 mIU/l. Since T3 suppresses TSH better than T4, administration of T3 would likely normalize the FT3/FT4 ratio at a lower, ostensibly more physiological, TSH level. This could be seen as a rationale for add-on T3 therapy.
Article
Objective: The interrelation between TSH, thyroid hormones, and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome. Design: This is a cross-sectional study that included subjects in a medical health check-up program at a single institution. Patients: The study included 132,346 participants (66,991 men and 65,355 women) aged over 18 years who had TSH, free T4 (FT4), and free T3 (FT3) levels within the institutional reference ranges. Measurements: TSH, FT4, FT3, and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, insulin, and glucose were measured. Results: There was a positive association between FT3/FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status, and menopausal status (in women). The FT3/FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women. Conclusions: TSH levels were positively associated with FT3/FT4 ratio within the euthyroid range. The higher FT3/FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/FT4 ratio has a better predictive power for metabolic syndrome than TSH. This article is protected by copyright. All rights reserved.