The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
The Colorado Thyroid Disease Prevalence Study
Abstract
CONTEXT: The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear. OBJECTIVE: To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests. DESIGN: Cross-sectional study. PARTICIPANTS: Participants in a statewide health fair in Colorado, 1995 (N = 25 862). MAIN OUTCOME MEASURES: Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire. RESULTS: The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) in this population was 9.5%, and the prevalence of decreased TSH levels was 2.2%. Forty percent of patients taking thyroid medications had abnormal TSH levels. Lipid levels increased in a graded fashion as thyroid function declined. Also, the mean total cholesterol and low-density lipoprotein cholesterol levels of subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than the corresponding mean lipid levels in euthyroid subjects. Symptoms were reported more often in hypothyroid vs euthyroid individuals, but individual symptom sensitivities were low. CONCLUSIONS: The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.
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In the citing paper
“However, 25-40% of patients on long-term levothyroxine treatment have a TSH concentration below or above the reference range.7,9,10”
From Hypothyroidism (2024) · cites this paper as [10]
In the citing paper
“The prevalence of hypothyroidism (subclinical and overt) ranges from 0•2% to 5•3% in Europe 3, 35- 37 and 0•3% to 3•7% in the USA, 10 depending on the definition used and the population.”
From Hypothyroidism (2024) · cites this paper as [10]
In the citing paper
“Approximately 10-15% of patients express dissatisfaction on levothyroxine despite TSH normalisation, due to persistent, residual symptoms that might reflect ongoing hypothyroidism.10,11”
From Hypothyroidism (2024) · cites this paper as [10]
In the citing paper
“60% of unselected euthyroid individuals have one or more symptom that may be attributable to hypothyroidism. 39”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [39]
In the citing paper
“Patientsaged 70 years or older may have fewer symptoms or signs and are less likely to exhibit someclassicsignssuchascoldintoleranceandweight gain compared with younger individuals (aged ≤ 55 years). 41”
From Hypothyroidism: A Review (2025) · cites this paper as [41]
In the citing paper
“The lack of specificity of hypothyroid symptoms and signs (49) and, particularly in case of autoimmune thyroid disease (AITD), the slow development of the pathologic state, renders difficult the assessment of the adequacy of the replacement therapy on a purely clinical basis.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [49]
In the citing paper
“There is some evidence that patients who report more symptoms and more recently developed symptoms are more likely to have hypothyroidism.10”
From Hypothyroidism (2024) · cites this paper as [10]
In the citing paper
“symptoms consistent with the presence of hypothyroidism are nonspecific and cannot be reliably used to differentiate those with hypothyroidism from euthyroid people. 39 -41”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [39]
In the citing paper
“Common symptoms include fatigue (74%-86%), weight gain (24%59%), cold intolerance (35%-65%), bradycardia (12%-19%), constipation(33%-41%),andcognitiveimpairment(45%-48%),includingmemorylossanddifficultyconcentrating. 41,42”
From Hypothyroidism: A Review (2025) · cites this paper as [41]
In the citing paper
“Common symptoms include fatigue (74%-86%), weight gain (24%59%), cold intolerance (35%-65%), bradycardia (12%-19%), constipation(33%-41%),andcognitiveimpairment(45%-48%),includingmemorylossanddifficultyconcentrating. 41,42”
From Hypothyroidism: A Review (2025) · cites this paper as [41]
In the citing paper
“Common symptoms include fatigue (74%-86%), weight gain (24%59%), cold intolerance (35%-65%), bradycardia (12%-19%), constipation(33%-41%),andcognitiveimpairment(45%-48%),includingmemorylossanddifficultyconcentrating. 41,42”
From Hypothyroidism: A Review (2025) · cites this paper as [41]
In the citing paper
“Common symptoms include fatigue (74%-86%), weight gain (24%59%), cold intolerance (35%-65%), bradycardia (12%-19%), constipation(33%-41%),andcognitiveimpairment(45%-48%),includingmemorylossanddifficultyconcentrating. 41,42”
From Hypothyroidism: A Review (2025) · cites this paper as [41]
In the citing paper
“Common symptoms include fatigue (74%-86%), weight gain (24%59%), cold intolerance (35%-65%), bradycardia (12%-19%), constipation(33%-41%),andcognitiveimpairment(45%-48%),includingmemorylossanddifficultyconcentrating. 41,42”
From Hypothyroidism: A Review (2025) · cites this paper as [41]
In the citing paper
“Common symptoms include fatigue (74%-86%), weight gain (24%59%), cold intolerance (35%-65%), bradycardia (12%-19%), constipation(33%-41%),andcognitiveimpairment(45%-48%),includingmemorylossanddifficultyconcentrating. 41,42”
From Hypothyroidism: A Review (2025) · cites this paper as [41]
In the citing paper
“In this respect it is noteworthy that hypothyroid symptoms were reported, despite a normal serum TSH, by 12.1% of 22,842 participants (1,525 of which were taking thyroid medication) in the Colorado Thyroid Disease Prevalence Study [17] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [17]
In the citing paper
“Despite this, studies show that for many people levothyroxine dosage is not adjusted as they age because either monitoring for thyroid dysfunction may be not be carried out or indicated dose adjustments identified by monitoring may not be implemented.9 10 11 12 13 14”
From Levothyroxine dose and risk of fractures in older adults: nested case-control study (2011) · cites this paper as [11]
In the citing paper
“Our study specifically focused on older adults, who have a higher baseline risk of fracture15 26 56 and are more vulnerable to excessive levothyroxine replacement.11 12 13 14”
From Levothyroxine dose and risk of fractures in older adults: nested case-control study (2011) · cites this paper as [11]
In the citing paper
“Hypothyroidism is mainly induced by autoimmune thyroid diseases and thyroidectomy (1, 2).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [2]
In the citing paper
“Even though its prevalence has not been precisely documented, non-optimal thyroxine therapy, as evidenced by TSH levels above (or below) the reference range, is common (Table 2)”
From Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report (2017) · cites this paper as [13]
In the citing paper
“The prevalence of hypothyroidism increases with age and subclinical hypothyroidism affects up to 15% of adults 65 years of age or older, when non-age-specific TSH reference ranges are used (9, 12–14).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [9]
In the citing paper
“Hypothyroid symptoms are non-specific and vary among patients, especially in the setting of subclinical hypothyroidism. The same symptoms are also quite common in euthyroid individuals and thus often overlap with the symptoms developed in patients with hypothyroidism (9).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [9]
In the citing paper
“Five to 24 percent of all patients taking L-T4 develop iatrogenic thyrotoxicosis (9, 11, 78, 81–83), a proportion that is even higher in the elderly [up to 41% (79)].”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [9]
In the citing paper
“It is recognized that up to one-quarter of the healthy normal population may have 'hypothyroid' symptoms such as lethargy and weight gain.14”
From Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee (2016) · cites this paper as [14]
In the citing paper
“Hypothyroidism is associated with a small but significant increase in lipid parameters (31), in particular, an elevation of low-density lipoproteins (LDLs) (32).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [31]
In the citing paper
“Overt hypothyroidism is diagnosed when serum TSH is elevated and circulating THs are low and is prevalent in 0.2% to 2% of nonpregnant adults (31,37).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [31]
In the citing paper
“The stated prevalence of SCH in published reports ranges from 4% to 10% of the adult population, being more common in women and older individuals (31,37).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [31]
In the citing paper
“most (at least 80%) patients with hypothyroidism have SCH (31).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [31]
Citations
Cites
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SERUM CHOLESTEROL, BLOOD PRESSURE, AND MORTALITY: IMPLICATIONS FROM A COHORT OF 361 662 MEN
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L-Thyroxine Therapy in Subclinical Hypothyroidism: A Double-Blind, Placebo-Controlled Trial
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Applications of a New Chemiluminometric Thyrotropin Assay to Subnormal Measurement*
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Relationship Between Vitamin D and Thyroid: An Enigma
Ashok, T., Palyam, V., Azam, A. T., Odeyinka, O., Alhashimi, R., Thoota, S., & Sange, I. (2022) · Cureus · doi:10.7759/cureus.21069 · Cited by 23
Levothyroxine sodium pentahydrate tablets – formulation considerations
Kaur, N., & Suryanarayanan, R. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.08.006 · Cited by 19
Managing symptoms in hypothyroid patients on adequate levothyroxine: a narrative review
Razvi, S., Mrabeti, S., & Luster, M. (2020) · Endocrine Connections · doi:10.1530/ec-20-0205 · Cited by 15
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The economic impact of switching from synthroid for the treatment of hypothyroidism
Khandelwal, N., Johns, B., Hepp, Z., & Castelli-Haley, J. (2018) · Journal of Medical Economics · doi:10.1080/13696998.2018.1443110 · Cited by 10
Oteri, V., Volpe, S., Lopes, M., Sceusa, G., Tumminia, A., Belfiore, A., Frasca, F., & Gullo, D. (2024) · Endocrine · doi:10.1007/s12020-024-04016-7 · Cited by 9
Subclinical thyroid dysfunction symptoms in older adults: cross-sectional study in UK primary care
McCahon, D., Haque, M. S., Parle, J., Hobbs, F. R., & Roberts, L. M. (2020) · British Journal of General Practice · doi:10.3399/bjgp20x708065 · Cited by 8
Hypothyroid Symptoms in Levothyroxine-Treated Patients
Freeman, M., Adunlin, G. A., Mercadel, C., Danzi, S., & Klein, I. (2019) · INNOVATIONS in pharmacy · doi:10.24926/iip.v10i3.2026 · Cited by 8
“The severity of each sign and symptom was rated on a scale from 0 to 4 points with the following numerical designations: absent (0), minimal (1), mild (2), moderate (3), and severe (4).”
Are multisource levothyroxine sodium tablets marketed in Egypt interchangeable?
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Biological variation in thyroid function tests in older adults and clinical implications
Riis, J., Westergaard, L., Karmisholt, J., Andersen, S. L., & Andersen, S. (2023) · Clinical Endocrinology · doi:10.1111/cen.14973 · Cited by 5
Pharmacodynamic and Therapeutic Actions of Levothyroxine
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Metadata
- Authors
- Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C.
- Affiliations
- University of Nebraska Medical Center (US)
- Abbott (United States) (US)
- University of Colorado Denver (US)
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2000-02-28
- Volume
- 160
- Issue
- 4
- Pages
- 526
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2140936682
- Cited by
- 2,824
- References
- 50
- Citations by year
- 2026: 49 · 2025: 64 · 2024: 86 · 2023: 138 · 2022: 158 · 2021: 151 · 2020: 191 · 2019: 147 · 2018: 148 · 2017: 166 · 2016: 161 · 2015: 140 · 2014: 144 · 2013: 147 · 2012: 132
- FWCI
- 31.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (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
- thyroid dysfunction, hypothyroidism, thyroid-stimulating hormone, thyroxine, serum lipids, cholesterol, LDL cholesterol, thyroid medication, cardiovascular risk
- MeSH terms
- Adult, Age Factors, Aged, Colorado, Cross-Sectional Studies, Diagnosis, Differential, Female, Humans, Lipids, Male, Middle Aged, Surveys and Questionnaires, Sex Factors, Thyroid Diseases, Thyroid Hormones, Prevalence
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