The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Thyroid Status, Disability and Cognitive Function, and Survival in Old Age
Abstract
CONTEXT: Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders. OBJECTIVES: To determine whether subclinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age. DESIGN, SETTING, AND PARTICIPANTS: A prospective, observational, population-based follow-up study within the Leiden 85-Plus Study of 87% of a 2-year birth cohort (1912-1914) in the municipality of Leiden, the Netherlands. A total of 599 participants were followed up from age 85 years through age 89 years (mean [SD] follow-up, 3.7 [1.4] years). MAIN OUTCOME MEASURES: Complete thyroid status at baseline; disability in daily life, depressive symptoms, cognitive function, and mortality from age 85 years through 89 years. RESULTS: Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status. The hazard ratio (HR) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 (95% confidence interval [CI], 0.63-0.94; P = .009). The HR for mortality per SD increase of 0.21 ng/dL (2.67 pmol/L) of free thyroxine increased 1.16-fold (95% CI, 1.04-1.30; P = .009). CONCLUSIONS: In the general population of the oldest old, elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span. However, evidence for not treating elderly individuals can only come from a well-designed, randomized placebo-controlled clinical trial.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“epidemiological studies suggest survival advantages both for low thyroid hormones and high TSH concentrations within the normal reference range in older individuals.34,132”
From Hypothyroidism (2024) · cites this paper as [34]
In the citing paper
“the distribution of serum TSH reference interval is right -shifted with age, 24 -26 giving an upper 97.5% confidence interval of around 7.5 mU/L in healthy elderly people. 2,3”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [26]
In the citing paper
“and in older individuals the prevalence is as high as 7% in individuals aged 85-89 years 34 when age-related reference ranges are not used.”
From Hypothyroidism (2024) · cites this paper as [34]
In the citing paper
“Longevity was associated with higher TSH concentrations in the Ashkenazi population (19) and confirmed by two Dutch studies (the Leiden 85-Plus Study and the Leiden Longevity Study) (33–35).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [33]
In the citing paper
“Men and women aged 85 years with abnormally high TSH concentrations according to the general reference range for younger people and abnormally low concentrations of fT4 had the lowest mortality rate during the 3.7-yr follow-up (33).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [33]
In the citing paper
“Epidemiological studies confirm survival advantages, both for low thyroid hormones and high TSH levels within the normal reference range [103, 104].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [103]
In the citing paper
“In addition, several studies of older patients have shown SCH to have either a protective or no impact on CV disease risk (103-105).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [103]
In the citing paper
“although one study of individuals age 85 years showed that a high serum TSH at baseline was associated with a favorable outcome compared with that of euthyroid contemporaries (29).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [29]
In the citing paper
“Notably, the Leiden 85+ study, a cohort study of 85-year-olds with a similar design to our study, found that subclinical hypothyroidism was associated with reduced all-cause mortality and cardiovascular mortality (29).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [29]
In the citing paper
“To examine whether our results were dependent upon the choice of confounders, we repeated analyses using the same confounding factors as Gussekloo et al (29), (age, sex, albumin, CRP, disease count, MMSE score, disability score, subjective health) and restricting survival to 4 years. Results were unchanged with only rT3 showing a significant relationship with mortality.”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [29]
In the citing paper
“In contrast with subclinical hypothyroidism, many previous studies have shown that low serum TSH is associated with poor outcomes, either increased all-cause or vascular mortality, or AF (12–14, 17, 29, 36, 37).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [29]
In the citing paper
“These findings, therefore, provide further reassurance that subclinical hypothyroidism is a benign state in advanced older age (2, 29).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [29]
In the citing paper
“some studies suggest an adverse effect of this state (8, 10, 22, 24) whereas others show a neutral or even protective effect on outcome (2, 17, 25, 29, 36, 37).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [29]
In the citing paper
“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 [29]
In the citing paper
“Some studies report increased overall mortality rates in SH subjects (374,379-383), especially older subjects, while others indicate no relation (384)(385)(386)(387).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [379]
Citations
Cites
The Colorado Thyroid Disease Prevalence Study
Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.4.526 · Cited by 2,824
Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study
Møller, J. T., Cluitmans, P. P., Rasmussen, L., Houx, P. J., Rasmussen, H., Canet, J., Rabbitt, P., Jolles, J., Larsen, K., Hanning, C. D., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(97)07382-0 · Cited by 2,407
Bianco, A. C., Salvatore, D., Gereben, B., Berry, M. J., & Larsen, P. R. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0455 · Cited by 1,853
Subclinical Thyroid Disease: Scientific Review and Guidelines for Diagnosis and Management
Surks, M. I., Ortiz, E., Daniels, G. H., Sawin, C. T., Col, N. F., Cobin, R. H., Franklyn, J. A., Hershman, J. M., Burman, K. D., Denke, M. A., et al. (2004) · JAMA · doi:10.1001/jama.291.2.228 · Cited by 1,800
Gueorguieva, R., & Krystal, J. H. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.3.310 · Cited by 1,529
Dwarf mice and the ageing process
Brown‐Borg, H. M., Borg, K. E., Meliska, C. J., & Bartke, A. (1996) · Nature · doi:10.1038/384033a0 · Cited by 1,091
Parle, J. V., Maisonneuve, P., Sheppard, M. C., Boyle, P., & Franklyn, J. A. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06067-6 · Cited by 669
American Thyroid Association guidelines for detection of thyroid dysfunction.
Ladenson, P., Singer, P., Ain, K., Bagchi, N., Bigos, S., Levy, E., Smith, S. A., Daniels, G., & Cohen, H. D. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.11.1573 · Cited by 658
Evolutionary medicine: from dwarf model systems to healthy centenarians?
Longo, V. D., & Finch, C. E. (2003) · Science · doi:10.1126/science.1077991 · Cited by 575
Cooper, D. S. (2001) · New England Journal of Medicine · doi:10.1056/nejm200107263450406 · Cited by 530
Successful Aging in the Oldest Old
von Faber, M., Wiel, A. B. D., van Exel, E. R., Gussekloo, J., Lagaay, A. M., van Dongen, E., Knook, D. L., van der Geest, S., & Westendorp, R. G. J. (2001) · Archives of Internal Medicine · doi:10.1001/archinte.161.22.2694 · Cited by 477
Self-citationLow-T3 syndrome: a strong prognostic predictor of death in patients with heart disease
Iervasi, G., Pingitore, A., Landi, P., Raciti, M., Ripoli, A., Scarlattini, M., L’Abbate, A., & Donato, L. (2003) · Circulation · doi:10.1161/01.cir.0000048124.64204.3f · Cited by 472
L-Thyroxine Therapy in Subclinical Hypothyroidism: A Double-Blind, Placebo-Controlled Trial
COOPER, D. S., HALPERN, R., WOOD, L. C., LEVIN, A. A., & RIDGWAY, E. C. (1984) · Annals of Internal Medicine · doi:10.7326/0003-4819-101-1-18 · Cited by 423
Meier, C., Staub, J.-J., Roth, C.-B., Guglielmetti, M., Kunz, M., Miserez, A. R., Drewe, J., Huber, P., Herzog, R. F. K., & Müller-Stich, B. P. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7973 · Cited by 397
Risk for Ischemic Heart Disease and All-Cause Mortality in Subclinical Hypothyroidism
Imaizumi, M., Akahoshi, M., Ichimaru, S., Nakashima, E., Hida, A., Soda, M., Usa, T., Ashizawa, K., Yokoyama, N., Maeda, R., et al. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031089 · Cited by 373
Accuracy of the 15‐item geriatric depression scale (GDS‐15) in a community sample of the oldest old
de Craen, A. J. M., Heeren, T. J., & Gussekloo, J. (2003) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.773 · Cited by 364 · cited 1×
“Participants with a GDS-15 score of 4 points or more were considered depressed.(19) Global cognitive function was assessed annually with the MMSE.”
MethodSelf-citationNyström, E., Caidahl, K., Fager, G., Wikkelsø, C., Lundberg, P. A., & Lindstedt, G. (1988) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1988.tb00250.x · Cited by 306
Helfand, M. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-2-200401200-00015 · Cited by 302
Caraccio, N., Ferrannini, E., & Monzani, F. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.4.8378 · Cited by 294
Euthyroid Sick Syndrome: An Overview
McIver, B., & Gorman, C. A. (1997) · Thyroid · doi:10.1089/thy.1997.7.125 · Cited by 258
Neurocognitive Aspects of Hypothyroidism
Dugbartey, A. T. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.13.1413 · Cited by 252
Toft, A. D. (2001) · New England Journal of Medicine · doi:10.1056/nejmcp010145 · Cited by 229
A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism
Kong, W. M., Sheikh, M. H., Lumb, P. J., Freedman, D. B., Crook, M. A., Doré, C. J., & Finer, N. (2002) · The American Journal of Medicine · doi:10.1016/s0002-9343(02)01022-7 · Cited by 223
The Snell dwarf mutation Pit1dw can increase life span in mice
Flurkey, K., Papaconstantinou, J., & Harrison, D. E. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00339-6 · Cited by 218
Jaeschke, R., Guyatt, G. H., Gerstein, H. C., Patterson, C., Molloy, W., Cook, D., Harper, S., Griffith, L. E., & Carbotte, R. M. (1996) · Journal of General Internal Medicine · doi:10.1007/bf02598988 · Cited by 216
Living Fast, Dying When? The Link between Aging and Energetics
Speakman, J. R., Selman, C., McLaren, J. S., & Harper, E. J. (2002) · Journal of Nutrition · doi:10.1093/jn/132.6.1583s · Cited by 216
A high response is not essential to prevent selection bias
Wiel, A. B. D., van Exel, E. R., de Craen, A. J. M., Gussekloo, J., Lagaay, A. M., Knook, D. L., & Westendorp, R. G. J. (2002) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(02)00505-x · Cited by 203
Self-citationScreening for Mild Thyroid Failure at the Periodic Health Examination
Danese, M. D. (1996) · JAMA · doi:10.1001/jama.1996.03540040029029 · Cited by 193
Col, N. F., Surks, M. I., & Daniels, G. H. (2004) · JAMA · doi:10.1001/jama.291.2.239 · Cited by 192
Testing cognitive function in elderly populations: the PROSPER study
Houx, P. J. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.4.385 · Cited by 153
Prolonged longevity of hypopituitary dwarf mice
Bartke, A., Brown‐Borg, H. M., Mattison, J. A., Kinney, B. A., Hauck, S., & Wright, C. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00205-9 · Cited by 134
Energy Expenditure of Rhesus Monkeys Subjected to 11 Years of Dietary Restriction
Blanc, S., Schoeller, D., Kemnitz, J., Weindruch, R., Colman, R., Newton, W., Wink, K., Baum, S., & Ramsey, J. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020405 · Cited by 128
OLSEN, T., Laurberg, P., & Weeke, J. (1978) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-47-5-1111 · Cited by 108
WHEN TO TREAT MILD HYPOTHYROIDISM
Ayala, A. R., Danese, M. D., & Ladenson, P. W. (2000) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70139-0 · Cited by 101
Pollock, M. A., Sturrock, A., Marshall, K., Davidson, K. M., Kelly, C. J. G., McMahon, A. D., & McLaren, E. H. (2001) · BMJ · doi:10.1136/bmj.323.7318.891 · Cited by 98 · cited 1×
“Furthermore, the outcomes of randomized placebo-controlled clinical trials evaluating the treatment effect of subclinical thyroid disease on symptoms and lipid levels are inconsistent.(5-11) Despite these ambiguities, policy makers have recommended screening and treatment of subclinical thyroid dysfunction to prevent…”
BackgroundThe controversy of the treatment of critically ill patients with thyroid hormone
Stathatos, N., Levetan, C. S., Burman, K. D., & Wartofsky, L. (2001) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1053/beem.2001.0164 · Cited by 90
Cognitive and neuropsychiatric aspects of subclinical hypothyroidism: Significance in the elderly
Davis, J. D., Stern, R. A., & Flashman, L. A. (2003) · Current Psychiatry Reports · doi:10.1007/s11920-003-0073-6 · Cited by 89
Mobbs, C. V., Bray, G. A., Atkinson, R. L., Bartke, A., Finch, C. E., Maratos–Flier, E., Crawley, J. N., & Nelson, J. F. (2001) · The Journals of Gerontology Series A · doi:10.1093/gerona/56.suppl_1.34 · Cited by 78
Pituitary-thyroid activity and longevity in neonatally thyroxine-treated rats
Ooka, H., Fujita, S., & Yoshimoto, E. (1983) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(83)90104-5 · Cited by 71
Disability in the Oldest Old: “Can Do” or “Do Do”?
Wiel, A. B. D., Gussekloo, J., de Craen, A. J. M., et al. (2001) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2001.49181.x · Cited by 65
Self-citationEffects of chronic hyperthyroidism on the lifespan of the rat
Ooka, H., & Shinkai, T. (1986) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(86)90052-7 · Cited by 57
Reporting delay and corrected incidence of multiple sclerosis
Esbjerg, S., Keiding, N., & Koch‐Henriksen, N. (1999) · Statistics in Medicine · doi:10.1002/(sici)1097-0258(19990715)18:13 · Cited by 38
High serum TSH levels are associated with depression in the elderly
Chueire, V. B., Silva, E. T. B., Perotta, E., Romaldini, J. H., & Ward, L. S. (2003) · Archives of Gerontology and Geriatrics · doi:10.1016/s0167-4943(02)00173-5 · Cited by 38
Nonthyroidal illness syndrome in off-pump coronary artery bypass grafting
Cerillo, A. G., Sabatino, L., Bevilacqua, S., Farneti, P. A., Scarlattini, M., Forini, F., & Glauber, M. (2003) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(02)03919-x · Cited by 28
Cited by
Sorted by citations
Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938
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
“There are observational data showing decreased mortality rates (258) and improved measures of well-being (259) in elderly persons with TSH levels that are above the traditional reference range (i.”
Global epidemiology of hyperthyroidism and hypothyroidism
Taylor, P. N., Albrecht, D., Scholz, A., Gutierrez-Buey, G., Lazarus, J. H., Dayan, C. M., & Okosieme, O. E. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2018.18 · Cited by 1,552
The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418
Subclinical 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
Self-citation
Metadata
- Authors
- Gussekloo, J.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Gussekloo, Jacobijn
- ORCID
- Gussekloo, Jacobijn
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2004-12-01
- Volume
- 292
- Issue
- 21
- Pages
- 2591
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2087194312
- Cited by
- 899
- References
- 44
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 28 · 2023: 30 · 2022: 70 · 2021: 50 · 2020: 32 · 2019: 39 · 2018: 52 · 2017: 49 · 2016: 49 · 2015: 55 · 2014: 53 · 2013: 67 · 2012: 56
- FWCI
- 17.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- 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 › Hormonal and reproductive studies
- Keywords
- subclinical thyroid dysfunction, older adults, oldest old, thyroid-stimulating hormone, free thyroxine, mortality, disability, cognitive function, depressive symptoms, thyroid screening, Leiden 85-plus Study
- MeSH terms
- Activities of Daily Living, Aged, Aged, 80 and over, Cognition Disorders, Depression, Female, Disabled Persons, Persons with Disabilities, Humans, Hypothyroidism, Male, Mortality, Prospective Studies, Thyroid Diseases, Thyrotropin, Thyroxine, Triiodothyronine, Proportional Hazards Models, Survival Analysis
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
