Subclinical thyroid disease

Cooper, David S; Biondi, Bernadette

doi:10.1016/s0140-6736(11)60276-6

Cited by 1,039Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Subclinical thyroid disease

Cooper, David S, Biondi, Bernadette·2012·The Lancet

DOI 10.1016/s0140-6736(11)60276-6

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Abstract

Subclinical thyroid diseases--subclinical hyperthyroidism and subclinical hypothyroidism--are common clinical entities that encompass mild degrees of thyroid dysfunction. The clinical significance of mild thyroid overactivity and underactivity is uncertain, which has led to controversy over the appropriateness of diagnostic testing and possible treatment. In this Seminar, we discuss the definition, epidemiology, differential diagnoses, risks of progression to overt thyroid disease, potential effects on various health outcomes, and management of subclinical hyperthyroidism and subclinical hypothyroidism. Treatment recommendations are based on the degree to which thyroid-stimulating hormone concentrations have deviated from normal and underlying comorbidities. Large-scale randomised trials are urgently needed to inform how to best care for individuals with subclinical thyroid disease.

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Subnormal serum TSH concentrations are frequently observed in black people and in some healthy cigarette smokers.
“Finally, subnormal serum TSH concentrations are frequently observed in black people and in some healthy cigarette smokers [3,5,25] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [5]
Serum free T4 and free T3 levels are generally normal to low-normal in people with central causes of low serum TSH.
“Serum free T 4 and free T 3 levels are generally normal to low-normal in people with the latter conditions [3,5,18] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [5]
The degree of TSH suppression is the best parameter for predicting the progression from subclinical to overt hyperthyroidism.
“The degree of TSH suppression is the best parameter for predicting the progression from subclinical to overt hyperthyroidism [3,5,18,31] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [5]
Endogenous subclinical hyperthyroidism is most commonly due to Graves' disease, toxic adenoma, and toxic multinodular goitre.
“Endogenous SHyper is most commonly due to Graves' disease (GD), toxic adenoma (TA) and toxic multinodular goitre (MNG) [3,5] ( table 1 ).”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [5]
Differences in the degree of TSH suppression, causes of subclinical hyperthyroidism, patient age, and duration of TSH suppression may influence the adverse consequences of endogenous subclinical hyperthyroidism.
“Differences in the degree of TSH suppression, causes of SHyper, patient age and duration of TSH suppression may influence the adverse consequences of Endo SHyper [3,5,30] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [5]

Subclinical hyperthyroidism may progress to overt hyperthyroidism and may be associated with increased cardiovascular and skeletal risk.
“SHyper may progress to overt hyperthyroidism and may be associated with increased cardiovascular and skeletal risk [3,5,18] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [5]
Autoimmune hypothyroidism is the most common cause of hypothyroidism at all ages, and the prevalence of thyroid autoimmunity increases with aging.
“Autoimmune hypothyroidism is the most common cause of hypothyroidism at all ages and the prevalence of thyroid autoimmunity increases with aging (23, 26, 27).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [27]
The presence of thyroid antibodies is associated with an increased risk of progression from subclinical to overt hypothyroidism.
“The presence of thyroid antibodies, which is associated with an increased risk of progression from subclinical to overt hypothyroidism, suggests a closer monitoring of thyroid function in subjects with thyroid antibodies (27, 52).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [27]
Subclinical hypothyroidism or high-normal TSH concentrations are associated with dyslipidemia, increased insulin resistance, and hypertension.
“Other epidemiological studies4,5,6,7 have also found an association between subclinical hypothyroidism or high-normal TSH concentrations (ie, serum TSH concentrations at the upper end of the normal range) and dyslipidemia, increased insulin resistance, and hypertension—components of metabolic syndrome.”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [4]
Elevated thyroid hormone levels negatively affect quality of life and cognitive function as well as the cardiovascular system in young and middle-aged populations.
“Elevated thyroid hormone levels have been reported to negatively affect quality of life and cognitive function as well as the cardiovascular system in young and middle-aged populations.4”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [4]
Women are at an increased risk of progression from subclinical to overt hypothyroidism.
“In general, it is well established that women are at an increased risk of progression from subclinical to overt hypothyroidism.4”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [4]
Treatment with levothyroxine is recommended when serum TSH concentrations reach 10 mIU/L or greater.
“A previous meta-analysis8 reported that subclinical hypothyroidism is associated with higher CVD risk, and thus treatment with levothyroxine is recommended when serum TSH concentrations reach 10 mIU/L or greater.4,31”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [4]
Randomized controlled trials of thyroid hormone treatment for subclinical hypothyroidism have given inconsistent evidence of benefit.
“The evidence for benefit in randomized controlled trials of thyroid hormone treatment in subclinical hypothyroidism is inconsistent and further studies are needed.3,15”
From Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee (2016) · cites this paper as [3]
Trials of levothyroxine in subclinical hypothyroidism using surrogate markers have shown improvement in left ventricular function, vascular endothelial function, atherogenic lipid particles, or cardiac mitochondrial function.
“Trials of levothyroxine in SCH using surrogate markers have shown improvement in LV function, vascular endothelial function, atherogenic lipid particles, or cardiac mitochondrial function (4,91,105-108).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [106]
It has widely been assumed that these associations are caused by subclinical hyperthyroidism with detrimental effects of excess thyroid hormone, despite serum thyroid hormones being within reference range.
“It has widely been assumed that these associations are caused by subclinical hyperthyroidism with detrimental effects of excess thyroid hormone, for instance its proarrhythmic effect on the heart leading to AF, despite the fact that serum thyroid hormones are within reference range (1, 13–15, 29, 41, 42).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [1]
Mild subclinical thyroid disease progresses slowly, at roughly 1% over five years, which suggests a need for long-term screening.
“Mild subclinical thyroid disease can progress at a low rate, suggesting a long-term screening program.”
From Thyroid dysfunction and diabetes mellitus: two closely associated disorders (2019) · cites this paper as [4]
Most studies of endogenous SH show decreased bone mineral density in postmenopausal women, but not in men or premenopausal women.
“Most studies of endogenous SH show decreased bone mineral density in postmenopausal women, but not in men or premenopausal women (406).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [406]

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Subclinical and Overt Thyroid Dysfunction and Risk of All-Cause Mortality and Cardiovascular Events: A Large Population Study
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MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease
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Authors: Cooper, D. S., & Biondi, B.
Affiliations: Johns Hopkins University (US)
University of Naples Federico II (IT)
Corresponding author: Cooper, David S
ORCID: Cooper, David S
Biondi, Bernadette
Venue: The Lancet
Publisher: Elsevier BV
Published: 2012-03
Volume: 379
Issue: 9821
Pages: 1142-1154
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(11)60276-6
OpenAlex: W2160393206
Cited by: 1,039
References: 151
Citations by year: 2026: 29 · 2025: 56 · 2024: 64 · 2023: 107 · 2022: 72 · 2021: 82 · 2020: 69 · 2019: 86 · 2018: 68 · 2017: 61 · 2016: 74 · 2015: 71 · 2014: 74 · 2013: 79 · 2012: 33
FWCI: 11.42
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: subclinical hyperthyroidism, subclinical hypothyroidism, thyroid dysfunction, thyroid-stimulating hormone, health outcomes, treatment guidelines, comorbidities, differential diagnosis
MeSH terms: Atrial Fibrillation, Cardiovascular Diseases, Diagnosis, Differential, Female, Humans, Hyperthyroidism, Hypothyroidism, Nutrition Surveys, Osteoporosis, Pregnancy, Pregnancy Complications, Quality of Life, Thyroid Hormones, Thyroiditis, Thyrotropin, Thyroxine, United States, Comorbidity, Disease Progression, Dyslipidemias

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