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Endocrinol Metab (Seoul)
. 2023 Aug 8;38(4):381–391. doi: 10.3803/EnM.2023.1778
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MANAGEMENT OF SUBCLINICAL HYPOTHYROIDISM: A FOCUS ON PROVEN HEALTH EFFECTS IN
THE 2023 KOREAN THYROID ASSOCIATION GUIDELINES

Eu Jeong Ku


EU JEONG KU

1Department of Internal Medicine, Seoul National University Hospital Healthcare
System Gangnam Center, Seoul, Korea
Find articles by Eu Jeong Ku
1,*, Won Sang Yoo


WON SANG YOO

2Department of Internal Medicine, Dankook University College of Medicine,
Cheonan, Korea
Find articles by Won Sang Yoo
2,*, Hyun Kyung Chung


HYUN KYUNG CHUNG

2Department of Internal Medicine, Dankook University College of Medicine,
Cheonan, Korea
Find articles by Hyun Kyung Chung
2,✉
 * Author information
 * Article notes
 * Copyright and License information

1Department of Internal Medicine, Seoul National University Hospital Healthcare
System Gangnam Center, Seoul, Korea
2Department of Internal Medicine, Dankook University College of Medicine,
Cheonan, Korea
✉

Corresponding author: Hyun Kyung Chung Department of Internal Medicine, Dankook
University College of Medicine, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, Korea
Tel: +82-41-550-3057, Fax: +82-41-556-3256, E-mail: chkendo@dankook.ac.kr

*

These authors contributed equally to this work.

This guideline has been originally written in Korean and published in the
International Journal of Thyroidology 2023;16:32-50.

Received 2023 Jul 15; Revised 2023 Jul 18; Accepted 2023 Jul 20; Issue date 2023
Aug.

Copyright © 2023 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative
Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the
original work is properly cited.

PMC Copyright notice
PMCID: PMC10475969  PMID: 37550859


ABSTRACT

Subclinical hypothyroidism (SCH) is characterized by elevated
thyroid-stimulating hormone (TSH) and normal free thyroxine levels. The Korean
Thyroid Association recently issued a guideline for managing SCH, which
emphasizes Korean-specific TSH diagnostic criteria and highlights the health
benefits of levothyroxine (LT4) treatment. A serum TSH level of 6.8 mIU/L is
presented as the reference value for diagnosing SCH. SCH can be classified as
mild (TSH 6.8 to 10.0 mIU/L) or severe (TSH >10.0 mIU/L), and patients can be
categorized as adults (age <70 years) or elderly (age ≥70 years), depending on
the health effects of LT4 treatment. An initial increase in serum TSH levels
should be reassessed with a subsequent measurement, including a thyroid
peroxidase antibody test, preferably 2 to 3 months after the initial assessment.
While LT4 treatment is not generally recommended for mild SCH in adults, it is
necessary for severe SCH in patients with underlying coronary artery disease or
heart failure and it may be considered for those with concurrent dyslipidemia.
Conversely, LT4 treatment is generally not recommended for elderly patients,
regardless of SCH severity. For those SCH patients who are prescribed LT4
treatment, the dosage should be personalized, and serum TSH levels should be
regularly monitored to maintain the optimal LT4 regimen.

Keywords: Subclinical hypothyroidism, Thyrotropin, Levothyroxine, Diagnosis,
Patient care management


INTRODUCTION

Subclinical hypothyroidism (SCH) is a condition characterized by normal levels
of serum free thyroxine (T4) despite elevated thyroid-stimulating hormone (TSH)
levels. SCH has often sparked considerable debate, primarily because it is
frequently detected during health screenings and can manifest in individuals
without any noticeable symptoms—hence the term “subclinical.” The prevalence of
SCH varies based on different criteria for the normal TSH range, race, iodine
intake, and age, but it is generally estimated to be between 5% and 15% [1]. The
National Health and Nutrition Examination Survey (NHANES) III study in the
United States reported an overall prevalence of 4.3% in the general population,
a figure that rose to 12.7% among individuals over the age of 65 [2]. A cohort
study in Korea found the prevalence to be 6.5% in men and 16.4% in women [3].
Most previously reported prevalence rates have been based on an upper normal
limit of TSH at 4.0 mIU/L [4,5]. However, TSH levels can vary depending on
geographical location, race, age, and sex. As a result, there have been a
continuous effort to establish appropriate TSH reference ranges for each region
[4,5]. Recently, 2023 Korean Thyroid Association (KTA) Management Guidelines for
Patients with Subclinical Hypothyroidism [6] introduced new diagnostic criteria
for SCH, emphasizing a regionspecific TSH reference range of 6.8 mIU/L based on
the sixth Korean National Health and Nutrition Examination Survey (KNHANES) [7].
This innovative approach also recognizes the heterogeneity of SCH and
categorizes the condition into mild and severe types, taking into account the
patient’s age and the distinctive implications of levothyroxine (LT4) treatment
in adults (under 70 years) and the elderly (70 years and older). These recent
KTA guidelines provide comprehensive recommendations on LT4 treatment selection,
stratified by the severity of SCH and the patient’s age. The guidelines also
consider key factors such as underlying coronary artery disease, heart failure,
and dyslipidemia, offering a more personalized approach to treatment. This
aligns with evidence-based clinical guidelines developed by relevant medical
societies worldwide, which have been established based on research findings from
the past decade (Table 1) [4-6,8-10].


TABLE 1.

Summary of Key Contents in Clinical Guidelines for Managing Subclinical
Hypothyroidism

Guidelines Consideration of LT4 treatment Observation without LT4 treatment ATA
(2012) [4] TSH >10 mIU/L, age <70 years TSH <10 mIU/L, age >70 years TSH 4–10
mIU/L, age <65 years, symptoms (+) TSH 4–10 mIU/L, age >65 years ETA (2013) [5]
TSH >10 mIU/L, age <70 years TSH <10 mIU/L symptoms (–), age <70 years TSH <10
mIU/L, age <70 years, symptoms (+) TSH <10 mIU/L, age >70 years TSH <10 mIU/L,
age >70 years, symptoms (+) or high cardiovascular (CV) risk Clinical practice
guideline (2017) [10] TSH >10 mIU/L, age <70 years TSH >10 mIU/L, age >70 years
Especially, symptoms (+) or CV risk factors 6 months of LT4 treatment in the
cases of TSH >4.5 and <7 mIU/L with symptoms or TSH >7 and <10 mIU/L, age <70
years symptoms (+) regardless of age, CV risk factors, TPOAb NICE guideline
(2018) [9] TSH >10 mIU/L, age <70 years TSH >10 mIU/L, age >70 years TSH 4–10
mIU/L, age <65 years, symptoms (+) TSH 4–10 mIU/L, age >65 years Clinical
practice guideline (2019) [8] Only women who are or trying to become pregnant or
patients with TSH >20 mIU/L Almost all adults KTA (2023) [6] TSH >10 mIU/L, age
<70 years TSH 6.8–10 mIU/L, age <70 years All elderly patients

Open in a new tab

LT4, levothyroxine; ATA, American Thyroid Association; TSH, thyroid-stimulating
hormone; ETA, European Thyroid Association; TPOAb, thyroid peroxidase antibody;
NICE, National Institute for Health and Care Excellence; KTA, Korean Thyroid
Association.

This review aims to provide a comprehensive overview of the 2023 KTA guidelines
for SCH management, highlighting their significance in improving the
understanding and management of this highly prevalent but frequently
under-recognized condition. Through this review, we hope to bridge the gap
between these practice guidelines and their application in clinical practice,
ultimately leading to better patient outcomes.


SUMMARY OF KEY CONTENTS OF THE 2023 KTA GUIDELINES FOR SCH MANAGEMENT


NEWLY PROPOSED DIAGNOSTIC CRITERIA FOR SCH

1. The TSH reference range for diagnosing SCH is based on the values obtained
from population studies in different regions and age groups without thyroid
disease (Strong, Moderate).

2. The TSH reference range in Korea is 0.6 to 6.8 mIU/L, based on the Sixth
KNHANES conducted from 2013 to 2015 (Strong, Moderate). However, differences in
measurements among TSH measurement kits must be considered when applying the
results.

3. SCH is classified as mild (TSH 6.8 to 10 mIU/L) or severe (TSH >10 mIU/L).
Given the distinct health effects of LT4 treatment with age, patients are
divided into adults and elderly, using 70 years as the cutoff (Strong,
Moderate).


LT4 TREATMENT SELECTION FOR SCH

1. LT4 treatment is generally not recommended for mild SCH in adults (<70 years)
(Weak, Moderate).

2. For severe SCH in adults (<70 years):

1) LT4 treatment is necessary if SCH is accompanied by underlying coronary
artery disease or heart failure (Strong, Moderate).

2) LT4 treatment can be considered for improving concomitant dyslipidemia (Weak,
Moderate).

3. LT4 treatment is not indicated for mild SCH in the elderly (≥70 years)
(Strong, High).

4. LT4 treatment is generally not recommended for severe SCH in the elderly (≥70
years) (Weak, Moderate).


CLINICAL CONSIDERATIONS IN THE DIAGNOSIS AND TREATMENT OF SCH

1. Following the initial detection of SCH, TSH levels, and thyroid peroxidase
(TPO) antibodies should be measured, preferably after 2 to 3 months, to guide
LT4 treatment decisions and predict the prognosis (Strong, Moderate).

2. High TSH and low free T4 levels at diagnosis, positive TPO antibodies, TSH
doubling upon follow-up, female sex, and thyroiditis are risk factors for
progression to overt hypothyroidism. Therefore, follow-up testing and treatment
should consider these factors (Weak, Moderate).

3. The required dosage of LT4 varies depending on weight and sex, and for
elderly patients or those at risk of cardiovascular disease, treatment should
begin with a dose of 12.5 to 25 μg/day. Thyroid function tests should be
monitored at intervals of 1 to 2 months, and the dosage adjusted with the aim of
normalizing serum TSH levels (Strong, Moderate).

4. SCH that is not treated with LT4 should be periodically monitored, with the
follow-up intervals determined based on the severity (Weak, Moderate).


THE RATIONALE FOR SETTING THE UPPER LIMIT OF NORMAL TSH AT 6.8 MIU/L

The upper limit for the TSH reference range is typically established by
referring to the manufacturer’s manual for the specific assay kit utilized in
the laboratory. It’s important to note that the upper normal limit for TSH can
vary based on geographical location, necessitating data analysis through cohort
studies to establish reference values. For instance, the NHANES in the United
States, which analyzed 17,353 disease-free individuals, reported a TSH upper
limit of 4.5 mIU/L [2]. Similarly, the Hanford Thyroid Disease Study, which
monitored individuals from 1950 to 2000 who showed no evidence of thyroid
disease, had negative anti-thyroid antibodies, were not on thyroid medications,
and had normal ultrasound results, reported a TSH upper limit of 4.1 mIU/L [11].
Based on these studies, the 2012 American Thyroid Association Clinical Practice
Guidelines for Hypothyroidism recommended that for third-generation TSH assays,
each laboratory’s reference range should determine the upper limit of normal. A
normal TSH reference range should consider the upper limit of 4.12 mIU/L in
iodine-sufficient regions [4]. In Europe, the Busselton Health Survey observed
1,100 individuals from 1981 to 1994 and proposed a normal upper limit of 4.10
mIU/L for all age groups [12]. Based on this study, the European Thyroid
Association (ETA) published the 2013 ETA Guideline: Management of Subclinical
Hypothyroidism, which set the TSH threshold at 4.0 mIU/L and classified TSH
levels between 4.0 and 10.0 mIU/L as mildly increased and levels above 10 as
severely increased [5].

TSH levels can fluctuate depending on iodine intake. Meta-analyses have revealed
that TSH levels tend to be higher in iodine-sufficient regions, and as a result,
they were generally higher in Asian and North American countries than in most
European countries [13]. In Korea, which is characterized by excessive iodine
intake due to geographical and cultural factors related to seaweed consumption,
the average urinary iodine concentration (UIC) measured in the KNHANES exceeded
the World Health Organization’s proposed adequate iodine intake level (adequate
level, 100 to 199 μg/L). Specifically, 66.3% of the population had UIC levels
above this range, and the average iodine intake level was 299.3 μg/L
(interquartile range, 158.8 to 699.8), indicating a high level of iodine intake
[14]. Therefore, it can be expected that TSH levels in Korea would be higher
than in other countries.

The Sixth KNHANES, conducted from 2013 to 2015, analyzed the TSH levels of 6,546
individuals without thyroid disorders. The average TSH concentration was found
to be 2.16 mIU/L. The reference range, which corresponds to the TSH
concentrations of 2.5% to 97.5% of the study population, was between 0.62 and
6.86 mIU/L (Table 2) [7,15]. Another retrospective analysis of health
examination data from approximately 20,000 individuals reported an average TSH
concentration of 2.38 mIU/L, with a reference range of 0.73 to 7.06 mIU/L (Table
3) [16]. TSH levels within the true reference range should not adversely affect
health. Therefore, cohort studies that analyze the health effects of various TSH
levels are necessary. These studies can provide insights into the potential
health impacts of different TSH levels and assist in establishing reference
ranges that accurately reflect health status. A prospective cohort study
conducted in Ansung, South Korea, observed 3,021 individuals over a 12-year
period. This study reported an increase in the prevalence and mortality of
cardiovascular diseases only in cases where TSH levels exceeded 6.57 mIU/L from
the 8th year of observation [3]. Interestingly, patients with TSH levels between
4.0 and 6.5 mIU/L did not exhibit any adverse health effects during the 12-year
observation period. This suggests that a higher upper normal limit of TSH (above
6.5 mIU/L) would not have detrimental health effects. In light of these
findings, the clinical practice guidelines for SCH presented by the KTA in 2023
established the upper normal limit at 6.8 mIU/L.


TABLE 2.

Serum Thyroid-Stimulating Hormone Concentrations (mIU/L) in the Korean Reference
Populationa,b

Study Age, yr All

--------------------------------------------------------------------------------

Men

--------------------------------------------------------------------------------

Women

--------------------------------------------------------------------------------

Mean Percentile

--------------------------------------------------------------------------------

Mean Percentile

--------------------------------------------------------------------------------

Mean Percentile

--------------------------------------------------------------------------------

2.5 Median 97.5 2.5 Median 97.5 2.5 Median 97.5 Kim et al. (2017) [7]a Total NA
0.62 2.23 6.86 NA 0.63 2.15 6.44 NA 0.60 2.31 7.21 Park et al. (2018) [15]b
10–19 2.33 0.63 2.45 7.37 2.44 0.75 2.47 6.92 2.31 0.57 2.39 7.47 20–29 2.15
0.67 2.25 6.05 2.13 0.66 2.22 6.09 2.22 0.67 2.26 6.00 30–39 2.05 0.61 2.07 6.42
2.00 0.68 2.04 6.05 2.12 0.50 2.17 6.54 40–49 2.04 0.58 2.09 6.20 1.94 0.59 1.97
5.96 2.16 0.55 2.20 7.20 50–59 2.20 0.49 2.30 8.11 2.06 0.53 2.08 7.02 2.38 0.42
2.56 9.19 60–69 2.17 0.56 2.21 7.77 2.07 0.53 2.13 7.35 2.26 0.56 2.28 7.87 >70
2.32 0.42 2.28 6.68 2.18 0.28 2.04 6.53 2.48 0.44 2.42 6.80 Total 2.16 0.59 2.23
7.03 2.09 0.62 2.14 6.57 2.24 0.56 2.31 7.43

Open in a new tab

This table was adapted and modified from Kim et al. (2017) [7] and Park et al.
(2018) [15].

NA, not available.

a

The reference population was defined as subjects with no prior history of
thyroid disease, no history of taking medications that could influence thyroid
function, no family history of thyroid disease, negative anti-thyroid peroxidase
antibody results, and serum free thyroxine levels in the reference range (0.89
to 1.76 ng/dL);

b

The reference population was defined as individuals without known thyroid
disease, family history of thyroid dysfunction and positive thyroid peroxidase
antibody, and current pregnancy.


TABLE 3.

Research Findings on the Serum TSH Concentrations in Normal Healthy Korean
Population

The 6th KNHANES Data from health check-ups (Asan Medical Center) Ansung cohorta
KLoSHAb Data from health check-ups (Yeungnam University Medical Center)
Published year 2017 2014 2010 2008 Number 6,564 5,778 3,399a and 940b 1,591 TSH,
mIU/L 2.23 (IQR, 1.55–3.18) 2.38 (95% CI, 0.72–7.79) 2.53±3.31a 3.49±7.12b
1.37±1.95 Reference rangec 0.62–6.86 0.73–7.06 NA 0.38–4.35 for men 0.35–6.42
for women

Open in a new tab

Values are expressed as mean±standard deviation.

TSH, thyroid-stimulating hormone; KNHANES, Korean National Health and Nutrition
Examination Survey; KLoSHA, the Korean Longitudinal Study on Health and Aging;
IQR, interquartile range; CI, confidence interval; NA, not available.

a

Ansung cohort;

b

KLoSHA;

c

2.5–97.5 percentile.


SCH IN DIFFERENT AGE GROUPS: STUDIES IN ELDERLY PATIENTS

Large-scale studies on the effectiveness of LT4 treatment in elderly SCH
patients have recently been published [17-20]. One such study utilized data from
four prospective cohorts within the Towards Understanding Longitudinal
International older People Studies (TULIPS) consortium to examine the
relationship between SCH and functional outcomes in individuals aged 80 years
and older [20]. The findings suggested that thyroid dysfunction was not linked
to disability in daily living, cognitive function, depressive symptoms, physical
function, or mortality in this demographic, indicating limited clinical
significance for this age group. The Thyroid Hormone replacement for Untreated
Older Adults with Subclinical Hypothyroidism (TRUST) study was designed to
explore the potential improvement of clinical symptoms in older adults (≥65
years) with SCH (mean baseline TSH, 6.4 mIU/L) who were administered LT4 (median
dose, 50 μg/day) or a placebo [18]. After 1 year of treatment, changes in
thyroid-related quality of life, hypothyroid symptoms, tiredness score,
hand-grip strength, cognitive function, blood pressure, weight, body-mass index,
and waist circumference were observed. However, no significant differences were
found when compared to the placebo group. In 2019, another randomized controlled
trial (RCT) was conducted with elderly patients (≥80 years), which found that
LT4 treatment for SCH had no impact on thyroid-related symptoms, cognitive
function, gait speed improvement, or reduction in cardiovascular disease and
overall mortality [19]. The Birmingham Elderly Thyroid study, published in 2010,
assessed mental states such as learning, memory, attention, and language skills
in older adults (≥65 years) with SCH after 12 months of LT4 treatment compared
to a placebo group [17]. The results showed no significant improvement.
Therefore, LT4 treatment in elderly patients does not appear to be effective in
preventing cardiovascular diseases, improving cognitive function, or alleviating
thyroid-related symptoms. Particularly in cases of mild SCH with TSH <10 mIU/L,
the KTA guidelines strongly recommend against treatment due to clear evidence.
For cases with TSH >10 mIU/L, research is limited and sufficient evidence is
still lacking. However, unless clear progression to overt hypothyroidism occurs,
it is generally recommended to proceed with caution rather than considering LT4
treatment as the first line of therapy.


CORONARY ARTERY DISEASE, HEART FAILURE, AND DYSLIPIDEMIA: IMPACT ON SCH
MANAGEMENT

SCH is associated not only with left ventricular diastolic dysfunction, but also
with a reduction in left ventricular systolic function during both rest and
exercise, heightened vascular resistance, arterial stiffness, endothelial
dysfunction, and a higher risk of atherosclerosis [21-25]. Moreover, numerous
intervention studies, inclusive of RCTs, have demonstrated that LT4 treatment
for SCH enhances cardiac structure and functional markers [26,27]. This suggests
that alterations in myocardial function, metabolic indicators, and vascular
function caused by SCH heighten the risk of major cardiovascular diseases, and
that these risks can be mitigated through LT4 treatment.

Recent meta-analyses that included large-scale cohort studies have reported
associations between specific cardiovascular conditions and SCH. Although these
meta-analyses did not conclusively establish an association between SCH and
cardiovascular diseases in general, they did reveal significantly increased
risks of congestive heart failure, coronary artery disease, and mortality
related to coronary artery disease in patients with severe SCH (TSH >10 mIU/L)
when compared to the euthyroid population [28-30]. Furthermore, a meta-analysis
that incorporated 35 retrospective cohort studies reported a 1.33-fold increased
risk of cardiovascular disease in SCH. This trend was more pronounced in the
high-risk group for cardiovascular disease, but it did not significantly
increase in individuals aged 65 or older [31].

Large-scale epidemiological studies have identified a linear correlation between
TSH levels and dyslipidemia. SCH is a condition that falls between overt
hypothyroidism and normal thyroid function, and it is characterized by elevated
levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C)
[32]. The European Prospective Investigation into Cancer (EPIC)-Norfolk study
specifically found that only women with SCH showed increases in total
cholesterol, LDL-C, and triglycerides, suggesting there may be gender-specific
variations in how SCH affects serum lipid profiles [33]. Recent meta-analyses
have further corroborated these findings, showing higher levels of total
cholesterol, LDL-C, and triglycerides in patients with SCH compared to those
with normal thyroid function [34]. However, no significant association was found
between SCH and high-density lipoprotein cholesterol levels.

In a small-scale RCT, LT4 treatment in patients with SCH reduced total
cholesterol and LDL-C levels, particularly in adults with severe SCH (TSH >12
mIU/L) [24,35-37]. Recent meta-analyses and systematic reviews have further
substantiated that LT4 therapy significantly decreases total cholesterol by 11.2
mg/dL and LDL-C by 8.5 mg/dL [38,39]. These findings suggest that LT4 treatment
could be a viable option for improving dyslipidemia in adults with severe SCH.
However, the effectiveness of LT4 treatment for dyslipidemia in patients with
mild SCH has produced inconsistent results [39].

Meanwhile, consistent benefits of LT4 treatment have not been proven in studies
targeting patients with SCH and concomitant depression, cognitive impairment,
and dementia [18,40]. Therefore, the 2023 KTA guidelines for SCH management do
not recommend LT4 treatment for the purpose of improving depression and
cognitive function.


LT4 TREATMENT: WHEN IS IT NECESSARY?

SCH may occur transiently or due to external factors such as environmental
conditions or the use of certain medications. Consequently, it is crucial to
conduct repeated thyroid function tests to verify the persistence of SCH. The
frequency of these tests may differ based on the patient’s age and the severity
of the condition. During follow-up, it is advisable to measure TPO antibodies to
evaluate the existence of autoimmune thyroiditis (Fig. 1).


FIG. 1.



Open in a new tab

Algorithm for levothyroxine (LT4) treatment in patients with subclinical
hypothyroidism (SCH).

Once a diagnosis of persistent SCH is confirmed, the treatment strategy should
consider the patient’s age and any existing health conditions. For elderly
patients (those aged 70 or older), it is generally preferable to monitor the
condition without treatment, especially in mild cases (TSH levels between 6.8
and 10 mIU/L). This is because the benefits of LT4 therapy are not substantiated
for this group. Conversely, for adults under 70, LT4 treatment is recommended,
particularly for severe cases (TSH levels above 10 mIU/L). This approach aims to
lower the risk of cardiovascular diseases through proactive medication.
Furthermore, LT4 treatment should be contemplated if TSH levels continue to
escalate, or if the patient has concurrent chronic thyroiditis, thyroid nodules,
or a history of thyroidectomy. A careful evaluation of these factors will assist
in determining the most suitable treatment plan for individuals with SCH, taking
into account their unique circumstances and potential risks.

A notable change from previous guidelines is that the presence of
hypothyroidism-related symptoms is no longer the sole criterion for initiating
LT4 treatment. Symptoms often associated with hypothyroidism, such as fatigue,
muscle discomfort, cold intolerance, dry skin, voice changes, and constipation,
are largely nonspecific. Despite this, earlier guidelines suggested considering
treatment for SCH based on symptom presence [4,5]. It is important to note;
however, that the studies used as evidence for these guidelines were primarily
small-scale observational studies. There is often uncertainty in classifying the
severity of the condition, which limits interpretation. Approximately 30% of
individuals with SCH did not exhibit symptoms, while conversely, 20% to 25% of
euthyroid individuals reported experiencing related symptoms [32]. Therefore,
the relationship between symptoms and biochemical TSH levels remains unclear.
Recent RCTs on SCH have prompted a shift in the perceived need for symptom-based
treatment. In a United Kingdom-based RCT involving 100 patients with SCH, the
group treated with LT4 showed lower levels of fatigue than the placebo group.
However, there were no significant differences in most other symptoms or quality
of life scores [41]. Meta-analyses have also demonstrated that LT4 treatment
does not significantly improve quality of life or symptom resolution [40]. In
the TRUST study involving elderly patients with SCH, those who received LT4
treatment did not show significant differences from the placebo group in symptom
improvement or fatigue reduction [18].

Based on these findings, the KTA treatment guidelines do not recommend LT4
treatment solely for the improvement of comorbid symptoms. The KTA guideline
also does not advocate for routine LT4 treatment. The link between SCH and
conditions such as depression, cognitive dysfunction, and dementia lacks
consistent and conclusive evidence, leading to their exclusion from treatment
consideration. Treatment is only recommended when there is clear evidence of
effectiveness, such as in cases with a high likelihood of progressing to overt
hypothyroidism, individuals at high-risk of cardiovascular disease, or for the
purpose of improving dyslipidemia. The 2019 publication by Bekkering et al. [8],
entitled “Thyroid hormones treatment for subclinical hypothyroidism: a clinical
practice guideline,” takes a similar position. The guideline strongly emphasizes
that general LT4 treatment in SCH is not beneficial. However, exceptions are
made for women preparing for pregnancy, individuals with TSH levels exceeding 20
mIU/L, those experiencing severe symptoms, and individuals under 30 years of age
[8].


UNMET NEEDS IN THE 2023 KTA GUIDELINES FOR SCH MANAGEMENT

Several issues have not been fully addressed in the 2023 KTA guidelines for SCH
management. First, the TSH fluctuations did not account for the variations among
different kits used in clinical settings. Table 4 summarizes the TSH measurement
kits used in each of the studies that provided the reference ranges for TSH
[1,3,7,11,12,15,16,42]. The reference range provided by the KNHANES, which
serves as the basis for the guidelines, is based on TSH results obtained through
a single assay method (electrochemiluminescence immunoassay, Roche Diagnostics,
Mannheim, Germany). However, different hospitals and institutions currently
utilize reference ranges provided by various kit manufacturers. This can lead to
discrepancies in the interpretation of normal versus abnormal results for the
same TSH elevation, causing confusion for patients. Therefore, it is essential
to clearly communicate and promote the intentions and recommendations of the
guidelines, while also considering potential variations in results when
different kits are used in healthcare facilities. Further research in this area
is anticipated in the near future.


TABLE 4.

Summary of TSH Measurement Kits Used in Studies Providing TSH Reference Ranges

Study Nation Study Method Kit Biondi et al. (2019) [1] USA NHANES III
Chemiluminescence immunometric assay Nichols Institute Diagnostics, San Juan
Capistrano, CA, USA Choi et al. (2010) [3] South Korea Ansung cohort and KLoSHA
Immunoradiometric assay CIS Bio International, IBA, Gif-sur-Yvette, France Kim
et al. (2017) [7] South Korea The 6th KNHANES Electrochemiluminescence
immunoassay Roche Diagnostics, Mannheim, Germany Hamilton et al. (2008) [11] USA
The Hanford Thyroid Disease Study Enzyme-linked immunosorbent assay Abbott IMX,
Abbott Laboratories, Abbott Park, IL, USA Bremner et al. (2012) [12] Western
Australia The Busselton Health Study Chemiluminescence immunoassay Siemens
Healthcare Diagnostics Products, Deerfield, IL, USA Park et al. (2017) [15]
South Korea The 6th KNHANES Electrochemiluminescence immunoassay Roche
Diagnostics, Mannheim, Germany Kim et al. (2015) [16] South Korea Data from
health check-ups of Asan Medical Center Immunoradiometric assay TSH-CTK-3 kit,
DiaSorin S.p.A., Saluggia, Italy Jang et al. (2008) [42] South Korea Data from
health check-ups of Yeungnam University Medical Center Enzyme-amplified
chemilumnescence Immulite 2000, third generation TSH, Los Angeles, CA, USA

Open in a new tab

TSH, thyroid-stimulating hormone; NHANES, National Health and Nutrition
Examination Survey; KLoSHA, the Korean Longitudinal Study on Health and Aging;
KNHANES, Korean National Health and Nutrition Examination Survey.

Second, while increasing the TSH threshold may reduce overdiagnosis, it could
potentially lead to an increase in undiagnosed conditions that necessitate
active treatment. This is especially crucial for women planning to become
pregnant or for children in their growth phases. It’s important to remember that
during the development of these recent KTA guidelines, children, adolescents,
pregnant women, and women attempting to conceive were not included in the target
group. According to the recently updated “Diagnosis and management of thyroid
disease during pregnancy and postpartum” by the KTA, it is recommended that
women planning to conceive maintain a TSH level below 4.0 mIU/L, and active
treatment for SCH is strongly recommended [43,44].

Lastly, there are certain ambiguities in some treatment guidelines. Although
there is a clear stance against treatment in elderly patients, guidelines are
not explicit about when treatment should commence. They suggest that treatment
should be considered when there is a progression in TSH elevation or when it
nears overt hypothyroidism. However, given the wide range of clinical
situations, it is challenging to apply a one-size-fits-all approach. The ETA,
the Latin American Thyroid Society, and the Society for Endocrinology,
Metabolism and Diabetes of South Africa have also recommended against LT4
treatment for elderly patients with mild SCH, where the health benefits have not
been proven [5,45,46]. Yet, the reality is that most clinicians, despite being
aware of the updated SCH management guidelines, continue to administer LT4
treatment to a significant number of elderly patients with mild SCH [47]. More
efforts are needed to widely disseminate the guidelines and understand the
obstacles to adherence in order to encourage appropriate management of SCH in
older individuals. Additionally, to establish more comprehensive and clear
treatment plans, adequate research is needed on the effects of LT4 treatment in
younger age groups, appropriate intervals and durations for follow-up
observations, and attempts to discontinue LT4 treatment.


CONCLUSIONS

The 2023 KTA guidelines for SCH management introduce new diagnostic criteria,
region-specific TSH reference ranges, and a classification of SCH into mild and
severe types based on age. These guidelines also provide comprehensive
recommendations for selecting LT4 treatment, considering the severity of SCH,
the patient’s age, and specific proven health effects. These guidelines are in
line with evidence-based clinical guidelines from other global medical
societies, underscoring the importance of personalized management. However,
there are still some unresolved issues, such as the variation in TSH reference
ranges among different kits, the effect of increased TSH thresholds on missed
diagnoses, the adjustment of treatment goals for patients with overt
hypothyroidism, and the need for more explicit guidelines on when to initiate
treatment, particularly in elderly patients. Bridging this gap between
guidelines and clinical practice will result in improved outcomes for patients
with this common but often overlooked condition.


ACKNOWLEDGMENTS

This research was supported by a grant from the Patient Centered Clinical
Research Coordinating Center funded by the Ministry of Health & Welfare,
Republic of Korea (grant number: HC19C0103040020). The funding source had no
role in the collection of the data or in the decision to submit the manuscript
for publication. The funding sources did not have a role in the design, data
collection, analysis, interpretation of data, or writing of the manuscript of
this study. We thank all members of the task force team (Yea Eun Kang, Kyeong
Jin Kim, Bo Hyun Kim, Tae-Yong Kim, Chang Ho Ahn, Jee Hee Yoon, Jong Min Lee,
Eui Dal Jung, Jae Hoon Chung, Yun Jae Chung, Won Bae Kim, Ka Hee Yi, Ho-Cheol
Kang, and Do Joon Park) who participated in the work of the 2023 Korean Thyroid
Association (KTA) Management Guidelines for Patients with Subclinical
Hypothyroidism and we also thank Young Joo Park and Eun Kyung Lee, the director
and secretary of the Practice Guideline Committee of KTA.


FOOTNOTES

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.


REFERENCES

 * 1.Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: a review.
   JAMA. 2019;322:153–60. doi: 10.1001/jama.2019.9052. [DOI] [PubMed] [Google
   Scholar]
 * 2.Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA,
   et al. Serum TSH, T(4), and thyroid antibodies in the United States
   population (1988 to 1994): National Health and Nutrition Examination Survey
   (NHANES III) J Clin Endocrinol Metab. 2002;87:489–99. doi:
   10.1210/jcem.87.2.8182. [DOI] [PubMed] [Google Scholar]
 * 3.Choi HS, Park YJ, Kim HK, Choi SH, Lim S, Park DJ, et al. Prevalence of
   subclinical hypothyroidism in two population based-cohort: Ansung and KLoSHA
   cohort in Korea. J Korean Thyroid Assoc. 2010;3:32–40. [Google Scholar]
 * 4.Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al.
   Clinical practice guidelines for hypothyroidism in adults: cosponsored by the
   American Association of Clinical Endocrinologists and the American Thyroid
   Association. Thyroid. 2012;22:1200–35. doi: 10.1089/thy.2012.0205. [DOI]
   [PubMed] [Google Scholar]
 * 5.Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al.
   2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J.
   2013;2:215–28. doi: 10.1159/000356507. [DOI] [PMC free article] [PubMed]
   [Google Scholar]
 * 6.Chung HK, Ku EJ, Yoo WS, Kang YE, Kim KJ, Kim BH, et al. 2023 Korean
   Thyroid Association management guidelines for patients with subclinical
   hypothyroidism. Int J Thyroidol. 2023;16:32–50. [Google Scholar]
 * 7.Kim WG, Kim WB, Woo G, Kim H, Cho Y, Kim TY, et al. Thyroid stimulating
   hormone reference range and prevalence of thyroid dysfunction in the Korean
   population: Korea National Health and Nutrition Examination Survey 2013 to
   2015. Endocrinol Metab (Seoul) 2017;32:106–14. doi:
   10.3803/EnM.2017.32.1.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
 * 8.Bekkering GE, Agoritsas T, Lytvyn L, Heen AF, Feller M, Moutzouri E, et al.
   Thyroid hormones treatment for subclinical hypothyroidism: a clinical
   practice guideline. BMJ. 2019;365:l2006. doi: 10.1136/bmj.l2006. [DOI]
   [PubMed] [Google Scholar]
 * 9.National Institute for Health and Care Excellence . London: NICE; 2018. CKS
   is only available in the UK [Internet] [cited 2023 Jul 20]. Available from:
   https://cks.nice.org.uk/hypothyroidism#!scenario:1. [Google Scholar]
 * 10.Peeters RP. Subclinical hypothyroidism. N Engl J Med. 2017;376:2556–65.
   doi: 10.1056/NEJMcp1611144. [DOI] [PubMed] [Google Scholar]
 * 11.Hamilton TE, Davis S, Onstad L, Kopecky KJ. Thyrotropin levels in a
   population with no clinical, autoantibody, or ultrasonographic evidence of
   thyroid disease: implications for the diagnosis of subclinical
   hypothyroidism. J Clin Endocrinol Metab. 2008;93:1224–30. doi:
   10.1210/jc.2006-2300. [DOI] [PMC free article] [PubMed] [Google Scholar]
 * 12.Bremner AP, Feddema P, Leedman PJ, Brown SJ, Beilby JP, Lim EM, et al.
   Age-related changes in thyroid function: a longitudinal study of a
   community-based cohort. J Clin Endocrinol Metab. 2012;97:1554–62. doi:
   10.1210/jc.2011-3020. [DOI] [PubMed] [Google Scholar]
 * 13.Xing D, Liu D, Li R, Zhou Q, Xu J. Factors influencing the reference
   interval of thyroid-stimulating hormone in healthy adults: a systematic
   review and meta-analysis. Clin Endocrinol (Oxf) 2021;95:378–89. doi:
   10.1111/cen.14454. [DOI] [PMC free article] [PubMed] [Google Scholar]
 * 14.Joung JY, Cho YY, Park SM, Kim TH, Kim NK, Sohn SY, et al. Effect of
   iodine restriction on thyroid function in subclinical hypothyroid patients in
   an iodine-replete area: a long period observation in a large-scale cohort.
   Thyroid. 2014;24:1361–8. doi: 10.1089/thy.2014.0046. [DOI] [PubMed] [Google
   Scholar]
 * 15.Park SY, Kim HI, Oh HK, Kim TH, Jang HW, Chung JH, et al. Age- and
   gender-specific reference intervals of TSH and free T4 in an iodine-replete
   area: data from Korean National Health and Nutrition Examination Survey IV
   (2013-2015) PLoS One. 2018;13:e0190738. doi: 10.1371/journal.pone.0190738.
   [DOI] [PMC free article] [PubMed] [Google Scholar]
 * 16.Kim M, Kim TY, Kim SH, Lee Y, Park SY, Kim HD, et al. Reference interval
   for thyrotropin in a ultrasonography screened Korean population. Korean J
   Intern Med. 2015;30:335–44. doi: 10.3904/kjim.2015.30.3.335. [DOI] [PMC free
   article] [PubMed] [Google Scholar]
 * 17.Parle J, Roberts L, Wilson S, Pattison H, Roalfe A, Haque MS, et al. A
   randomized controlled trial of the effect of thyroxine replacement on
   cognitive function in community-living elderly subjects with subclinical
   hypothyroidism: the Birmingham Elderly Thyroid study. J Clin Endocrinol
   Metab. 2010;95:3623–32. doi: 10.1210/jc.2009-2571. [DOI] [PubMed] [Google
   Scholar]
 * 18.Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RG, Mooijaart SP, et
   al. Thyroid hormone therapy for older adults with subclinical hypothyroidism.
   N Engl J Med. 2017;376:2534–44. doi: 10.1056/NEJMoa1603825. [DOI] [PubMed]
   [Google Scholar]
 * 19.Mooijaart SP, Du Puy RS, Stott DJ, Kearney PM, Rodondi N, Westendorp RG,
   et al. Association between levothyroxine treatment and thyroid-related
   symptoms among adults aged 80 years and older with subclinical
   hypothyroidism. JAMA. 2019;322:1977–86. doi: 10.1001/jama.2019.17274. [DOI]
   [PMC free article] [PubMed] [Google Scholar]
 * 20.Du Puy RS, Poortvliet RK, Mooijaart SP, den Elzen WP, Jagger C, Pearce SH,
   et al. Outcomes of thyroid dysfunction in people aged eighty years and older:
   an individual patient data meta-analysis of four prospective studies (towards
   understanding longitudinal international older people studies consortium)
   Thyroid. 2021;31:552–62. doi: 10.1089/thy.2020.0567. [DOI] [PubMed] [Google
   Scholar]
 * 21.Yazici M, Gorgulu S, Sertbas Y, Erbilen E, Albayrak S, Yildiz O, et al.
   Effects of thyroxin therapy on cardiac function in patients with subclinical
   hypothyroidism: index of myocardial performance in the evaluation of left
   ventricular function. Int J Cardiol. 2004;95:135–43. doi:
   10.1016/j.ijcard.2003.05.015. [DOI] [PubMed] [Google Scholar]
 * 22.Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, et al.
   Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism:
   beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab.
   2003;88:3731–7. doi: 10.1210/jc.2003-030039. [DOI] [PubMed] [Google Scholar]
 * 23.Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, et al.
   Effect of levothyroxine on cardiac function and structure in subclinical
   hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol
   Metab. 2001;86:1110–5. doi: 10.1210/jcem.86.3.7291. [DOI] [PubMed] [Google
   Scholar]
 * 24.Monzani F, Caraccio N, Kozakowa M, Dardano A, Vittone F, Virdis A, et al.
   Effect of levothyroxine replacement on lipid profile and intima-media
   thickness in subclinical hypothyroidism: a double-blind, placebo-controlled
   study. J Clin Endocrinol Metab. 2004;89:2099–106. doi:
   10.1210/jc.2003-031669. [DOI] [PubMed] [Google Scholar]
 * 25.Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC.
   Subclinical hypothyroidism is an independent risk factor for atherosclerosis
   and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern
   Med. 2000;132:270–8. doi: 10.7326/0003-4819-132-4-200002150-00004. [DOI]
   [PubMed] [Google Scholar]
 * 26.Shakoor SK, Aldibbiat A, Ingoe LE, Campbell SC, Sibal L, Shaw J, et al.
   Endothelial progenitor cells in subclinical hypothyroidism: the effect of
   thyroid hormone replacement therapy. J Clin Endocrinol Metab. 2010;95:319–22.
   doi: 10.1210/jc.2009-1421. [DOI] [PubMed] [Google Scholar]
 * 27.Cabral MD, Teixeira PF, Silva NA, Morais FF, Soares DV, Salles E, et al.
   Normal flow-mediated vasodilatation of the brachial artery and carotid artery
   intima-media thickness in subclinical hypothyroidism. Braz J Med Biol Res.
   2009;42:426–32. doi: 10.1590/s0100-879x2009000500005. [DOI] [PubMed] [Google
   Scholar]
 * 28.Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, et al.
   Subclinical hypothyroidism and the risk of coronary heart disease and
   mortality. JAMA. 2010;304:1365–74. doi: 10.1001/jama.2010.1361. [DOI] [PMC
   free article] [PubMed] [Google Scholar]
 * 29.Gencer B, Collet TH, Virgini V, Bauer DC, Gussekloo J, Cappola AR, et al.
   Subclinical thyroid dysfunction and the risk of heart failure events: an
   individual participant data analysis from 6 prospective cohorts. Circulation.
   2012;126:1040–9. doi: 10.1161/CIRCULATIONAHA.112.096024. [DOI] [PMC free
   article] [PubMed] [Google Scholar]
 * 30.Chaker L, Baumgartner C, den Elzen WP, Ikram MA, Blum MR, Collet TH, et
   al. Subclinical hypothyroidism and the risk of stroke events and fatal
   stroke: an individual participant data analysis. J Clin Endocrinol Metab.
   2015;100:2181–91. doi: 10.1210/jc.2015-1438. [DOI] [PMC free article]
   [PubMed] [Google Scholar]
 * 31.Moon S, Kim MJ, Yu JM, Yoo HJ, Park YJ. Subclinical hypothyroidism and the
   risk of cardiovascular disease and allcause mortality: a meta-analysis of
   prospective cohort studies. Thyroid. 2018;28:1101–10. doi:
   10.1089/thy.2017.0414. [DOI] [PubMed] [Google Scholar]
 * 32.Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease
   prevalence study. Arch Intern Med. 2000;160:526–34. doi:
   10.1001/archinte.160.4.526. [DOI] [PubMed] [Google Scholar]
 * 33.Boekholdt SM, Titan SM, Wiersinga WM, Chatterjee K, Basart DC, Luben R, et
   al. Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk
   prospective population study. Clin Endocrinol (Oxf) 2010;72:404–10. doi:
   10.1111/j.1365-2265.2009.03640.x. [DOI] [PubMed] [Google Scholar]
 * 34.Liu XL, He S, Zhang SF, Wang J, Sun XF, Gong CM, et al. Alteration of
   lipid profile in subclinical hypothyroidism: a meta-analysis. Med Sci Monit.
   2014;20:1432–41. doi: 10.12659/MSM.891163. [DOI] [PMC free article] [PubMed]
   [Google Scholar]
 * 35.Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical
   hypothyroidism: response to levothyroxine replacement, a randomized
   placebo-controlled study. J Clin Endocrinol Metab. 2002;87:1533–8. doi:
   10.1210/jcem.87.4.8378. [DOI] [PubMed] [Google Scholar]
 * 36.Meier C, Staub JJ, Roth CB, Guglielmetti M, Kunz M, Miserez AR, et al.
   TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical
   symptoms in subclinical hypothyroidism: a double blind, placebo-controlled
   trial (Basel Thyroid Study) J Clin Endocrinol Metab. 2001;86:4860–6. doi:
   10.1210/jcem.86.10.7973. [DOI] [PubMed] [Google Scholar]
 * 37.Teixeira PF, Reuters VS, Ferreira MM, Almeida CP, Reis FA, Melo BA, et al.
   Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a
   placebo-controlled double-blind clinical trial. Horm Metab Res. 2008;40:50–5.
   doi: 10.1055/s-2007-993216. [DOI] [PubMed] [Google Scholar]
 * 38.Abreu IM, Lau E, de Sousa Pinto B, Carvalho D. Subclinical hypothyroidism:
   to treat or not to treat, that is the question!: a systematic review with
   meta-analysis on lipid profile. Endocr Connect. 2017;6:188–99. doi:
   10.1530/EC-17-0028. [DOI] [PMC free article] [PubMed] [Google Scholar]
 * 39.Li X, Wang Y, Guan Q, Zhao J, Gao L. The lipid-lowering effect of
   levothyroxine in patients with subclinical hypothyroidism: a systematic
   review and meta-analysis of randomized controlled trials. Clin Endocrinol
   (Oxf) 2017;87:1–9. doi: 10.1111/cen.13338. [DOI] [PubMed] [Google Scholar]
 * 40.Feller M, Snel M, Moutzouri E, Bauer DC, de Montmollin M, Aujesky D, et
   al. Association of thyroid hormone therapy with quality of life and
   thyroid-related symptoms in patients with subclinical hypothyroidism: a
   systematic review and meta-analysis. JAMA. 2018;320:1349–59. doi:
   10.1001/jama.2018.13770. [DOI] [PMC free article] [PubMed] [Google Scholar]
 * 41.Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial
   effect of L-thyroxine on cardiovascular risk factors, endothelial function,
   and quality of life in subclinical hypothyroidism: randomized, crossover
   trial. J Clin Endocrinol Metab. 2007;92:1715–23. doi: 10.1210/jc.2006-1869.
   [DOI] [PubMed] [Google Scholar]
 * 42.Jang YY, Kim CY, Hwang TY, Kim KD, Lee CH. Reference interval of serum
   thyroid hormones in healthy Korean adults. J Prev Med Public Health.
   2008;41:128–34. doi: 10.3961/jpmph.2008.41.2.128. [DOI] [PubMed] [Google
   Scholar]
 * 43.Ahn HY, Yi KH. Diagnosis and management of thyroid disease during
   pregnancy and postpartum: 2023 revised Korean Thyroid Association Guidelines.
   Endocrinol Metab (Seoul) 2023;38:289–94. doi: 10.3803/EnM.2023.1696. [DOI]
   [PMC free article] [PubMed] [Google Scholar]
 * 44.Yi KH, Ahn HY, Kim JH, Park SY, Yoo WS, Jung KY, et al. 2023 Revised
   Korean Thyroid Association guidelines for the diagnosis and management of
   thyroid disease during pregnancy and postpartum. Int J Thyroidol.
   2023;16:51–88. doi: 10.3803/EnM.2023.1696. [DOI] [PMC free article] [PubMed]
   [Google Scholar]
 * 45.Brenta G, Vaisman M, Sgarbi JA, Bergoglio LM, Andrada NC, Bravo PP, et al.
   Clinical practice guidelines for the management of hypothyroidism. Arq Bras
   Endocrinol Metabol. 2013;57:265–91. doi: 10.1590/s0004-27302013000400003.
   [DOI] [PubMed] [Google Scholar]
 * 46.Dave JA, Klisiewicz A, Bayat Z, Mohamed NA, Stevens Z, Mollentze WF, et
   al. SEMDSA/ACE-SA guideline for the management of hypothyroidism in adults. J
   Endocrinol Metab Diabetes S Afr. 2015;20:18–26. [Google Scholar]
 * 47.Razvi S, Arnott B, Teare D, Hiu S, O’Brien N, Pearce SH. Multinational
   survey of treatment practices of clinicians managing subclinical
   hypothyroidism in older people in 2019. Eur Thyroid J. 2021;10:330–8. doi:
   10.1159/000509228. [DOI] [PMC free article] [PubMed] [Google Scholar]

--------------------------------------------------------------------------------

Articles from Endocrinology and Metabolism are provided here courtesy of Korean
Endocrinology Society


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 * Abstract
 * INTRODUCTION
 * SUMMARY OF KEY CONTENTS OF THE 2023 KTA GUIDELINES FOR SCH MANAGEMENT
 * THE RATIONALE FOR SETTING THE UPPER LIMIT OF NORMAL TSH AT 6.8 mIU/L
 * SCH IN DIFFERENT AGE GROUPS: STUDIES IN ELDERLY PATIENTS
 * CORONARY ARTERY DISEASE, HEART FAILURE, AND DYSLIPIDEMIA: IMPACT ON SCH
   MANAGEMENT
 * LT4 TREATMENT: WHEN IS IT NECESSARY?
 * UNMET NEEDS IN THE 2023 KTA GUIDELINES FOR SCH MANAGEMENT
 * CONCLUSIONS
 * Acknowledgments
 * Footnotes
 * REFERENCES


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