The DOI matches its Crossref record; 528 of the 539 references it cites were found in a registry or an index.
The Clinical Significance of Subclinical Thyroid Dysfunction
Abstract
Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's age.
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“Cardiac AEs, including tachycardia, palpitations and atrial fibrillation, arise from increased myocardial oxygen consumption and enhanced β‐adrenergic sensitivity.”
From Risk of cardiac, neuropsychiatric and musculoskeletal adverse events with levothyroxine: Systematic review (2026) · cites this paper as [5]
In the citing paper
“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 [3]
In the citing paper
“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 [3]
In the citing paper
“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 [3]
In the citing paper
“These results are consistent with literature observing changes in type I interferon activity (Li et al. 2015) and thyroid hormone signaling with aging (Biondi and Cooper 2008; Gesing et al. 2012; Visser et al. 2016), as well as our differential expression analysis.”
From Murine single-cell RNA-seq reveals cell-identity- and tissue-specific trajectories of aging (2019) · cites this paper as Biondi and Cooper 2008
In the citing paper
“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 [3]
In the citing paper
“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 [3]
In the citing paper
“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 [3]
In the citing paper
“Suppression of TSH may also be iatrogenic (exogenous) due to thyroid hormone overtreatment, either intentionally (in patients with thyroid cancer), unintentionally (in patients with hypothyroidism) or surreptitiously [2,3] ( table 1 ).”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [3]
In the citing paper
“In addition, increased arterial stiffness and a low renin state are contributory factors leading to blood pressure and vascular dysregulation due to the lack of the normal vasodilatory effects of T 3 (4,43)”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [4]
In the citing paper
“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 [4]
In the citing paper
“Consequently, definitions of hypothyroidism or hyperthyroidism were adjusted, introducing new laboratory-based and TSH-derived disease entities of subclinical hypothyroidism and hyperthyroidism, which are defined by an abnormal TSH level while FT3 and FT4 still dwell within their reference ranges (176–178).”
From Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment (2015) · cites this paper as [177]
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Mandel, S. J., Spencer, C. A., & Hollowell, J. G. (2005) · Thyroid · doi:10.1089/thy.2005.15.44 · Cited by 184
Psychopathological and cognitive features in subclinical hypothyroidism
Baldini, I., Vita, A., Mauri, M. C., Amodei, V., Carrisi, M., Bravin, S., & CANTALAMESSA, L. (1997) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(97)00089-4 · Cited by 183
STATISTICAL METHODS APPLIED TO THE DIAGNOSIS OF HYPOTHYROLDISM
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Hamblin, P. S., Dyer, S. A., MOHR, V. S., GRAND, B. A. L., Lim, C., Tuxen, D. V., Topliss, D. J., & Stockigt, J. R. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-62-4-717 · Cited by 182
Tunbridge, W. M. G., Evered, D. C., Hall, R., Appleton, D. R., BREWIS, M., CLARK, F., Evans, J. G., Young, E. T., Bird, T., & Smith, P. (1977) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1977.tb01341.x · Cited by 177
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Lack of association between serum TSH or free T4 and body mass index in euthyroid subjects
Manji, N., Boelaert, K., Sheppard, M. C., Holder, R. L., Gough, S. C. L., & Franklyn, J. A. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02433.x · Cited by 167
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Flagged first, then by citations
11 of the 539 references couldn’t be matched to a known paper.
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Cited by
Sorted by citations
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
“It is well known that in mild primary hypothyroidism, serum T3 is kept normal in the face of a low serum T4 and mildly elevated TSH (4).”
Self-citationSubclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality
Rodondi, N., den Elzen, W. P. J., Bauer, D. C., Cappola, A. R., Razvi, S., Walsh, J. P., Åsvold, B. O., Iervasi, G., Imaizumi, M., Collet, T.-H., et al. (2010) · JAMA · doi:10.1001/jama.2010.1361 · Cited by 1,216
The epidemiology of thyroid disease
Vanderpump, M. P. J. (2011) · British Medical Bulletin · doi:10.1093/bmb/ldr030 · Cited by 1,179
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Bailey, L. B., Stover, P. J., McNulty, H., Fenech, M. F., Gregory, J. F., Mills, J. L., Pfeiffer, C. M., Fazili, Z., Zhang, M., Ueland, P. M., et al. (2015) · Journal of Nutrition · doi:10.3945/jn.114.206599 · Cited by 1,170
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Metadata
- Authors
- Biondi, B., & Cooper, D. S.
- Affiliations
- University of Naples Federico II (IT)
- Johns Hopkins University (US)
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2007-11-08
- Volume
- 29
- Issue
- 1
- Pages
- 76-131
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2043015190
- Cited by
- 1,418
- References
- 539
- Citations by year
- 2026: 58 · 2025: 62 · 2024: 55 · 2023: 63 · 2022: 83 · 2021: 70 · 2020: 75 · 2019: 83 · 2018: 83 · 2017: 87 · 2016: 85 · 2015: 81 · 2014: 82 · 2013: 96 · 2012: 101
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (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 thyroid dysfunction, subclinical hyperthyroidism, subclinical hypothyroidism, thyroid-stimulating hormone, free thyroxine, free T3, cardiovascular risk, bone metabolism, thyroid hormone replacement, thyroid screening, tissue effects
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Calcification, Physiologic, Cardiovascular Diseases, Child, Child, Preschool, Cognition, Diagnosis, Differential, Humans, Hyperthyroidism, Hypothalamus, Hypothyroidism, Infant, Infant, Newborn, Middle Aged, Pituitary Gland, Quality of Life, Reference Values, Risk Factors, Thyroid Diseases, Thyroid Gland, Thyrotropin, Thyroxine, Triiodothyronine, Neonatal Screening, MEDLINE
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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