CoChat
Sign Up
Cited by 38Thyroid Disorders and TreatmentsDementia and Cognitive Impairment ResearchThyroid and Parathyroid Surgery

Endogenous and exogenous thyrotoxicosis and risk of incident cognitive disorders in older adults.

Open access
Adams, Roy, Oh, Esther S., Yasar, Sevil, Lyketsos, Constantine G., Mammen, Jennifer S.·2023·JAMA Internal Medicine
DOI 10.1001/jamainternmed.2023.5619PMC PMC10594176
Open this paper in CoChat — free account

Abstract

Importance: Thyroid hormone is among the most common prescriptions in the US and up to 20% may be overtreated. Endogenous hyperthyroidism may be a risk factor for dementia, but data are limited for iatrogenic thyrotoxicosis. Objective: To determine whether thyrotoxicosis, both endogenous and exogenous, is associated with increased risk of cognitive disorders. Design, Setting, and Participants: This cohort study performed a longitudinal time-varying analysis of electronic health records for patients receiving primary care in the Johns Hopkins Community Physicians Network between January 1, 2014, and May 6, 2023. Patients 65 years and older with at least 2 visits 30 days apart to their primary care physicians were eligible. None of the 65 931 included patients had a history of low thyrotropin (TSH) level or cognitive disorder diagnoses within 6 months of their first visit. Data analysis was performed from January 1 through August 5, 2023. Exposure: The exposure variable was a low TSH level, characterized based on the clinical context as due to endogenous thyrotoxicosis, exogenous thyrotoxicosis, or unknown cause, excluding those attributable to acute illness or other medical factors such as medications. Main Outcomes and Measures: The outcome measure was cognitive disorders, including mild cognitive impairment and all-cause dementia, to improve sensitivity and account for the underdiagnosis of dementia in primary care. Results: A total of 65 931 patients were included in the analysis (median [IQR] age at first visit, 68.0 [65.0-74.0] years; 37 208 [56%] were female; 46 106 [69.9%] were White). Patients exposed to thyrotoxicosis had cognitive disorder incidence of 11.0% (95% CI, 8.4%-14.2%) by age 75 years vs 6.4% (95% CI, 6.0%-6.8%) for those not exposed. After adjustment, all-cause thyrotoxicosis was significantly associated with risk of cognitive disorder diagnosis (adjusted hazard ratio, 1.39; 95% CI, 1.18-1.64; P < .001) across age groups. When stratified by cause and severity, exogenous thyrotoxicosis remained a significant risk factor (adjusted hazard ratio, 1.34; 95% CI, 1.10-1.63; P = .003) with point estimates suggestive of a dose response. Conclusions and Relevance: In this cohort study among patients 65 years and older, a low TSH level from either endogenous or exogenous thyrotoxicosis was associated with higher risk of incident cognitive disorder. Iatrogenic thyrotoxicosis is a common result of thyroid hormone therapy. With thyroid hormone among the most common prescriptions in the US, understanding the negative effects of overtreatment is critical to help guide prescribing practice.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1001/jamainternmed.2023.5619

Cites

23 of 26 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Serum thyrotropin levels below or above the reference range while taking levothyroxine have been associated with increased risk of adverse cardiovascular events.

    “Serum thyrotropin levels below or above the reference range while taking levothyroxine have been associated with increased risk of adverse cardiovascular events. 72-75”

    From Hypothyroidism: A Review (2025) · cites this paper as [75]

    The Results report an association between low TSH, including exogenous thyrotoxicosis, and incident cognitive disorders in older adults. The Introduction mentions elevated TSH, but neither passage addresses whether TSH below or above the reference range during levothyroxine treatment is associated with adverse cardiovascular events. Searches for cardiovascular events and levothyroxine found no such finding in our copy. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Adams, R., Oh, E. S., Yasar, S., Lyketsos, C. G., & Mammen, J. S.
Affiliations
  • Johns Hopkins University (US)
  • Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
Corresponding author
Mammen, Jennifer S.
ORCID
Venue
JAMA Internal Medicine
Publisher
American Medical Association (AMA)
Published
2023-12-01
Volume
183
Issue
12
Pages
1324
ISSN
2168-6106 (ISSN-L)
DOI
10.1001/jamainternmed.2023.5619
PMC
PMC10594176
OpenAlex
W4387865593
Cited by
38
References
25
Citations by year
2026: 11 · 2025: 13 · 2024: 13 · 2023: 1
FWCI
7.75
Type
journal article
Language
en
Open access
Locations
  • JAMA Internal Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (R01AG057725, R01AG064256, K25AG083064, P30AG066507, R01AG076525)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords
thyrotoxicosis, iatrogenic hyperthyroidism, cognitive disorders, dementia, mild cognitive impairment, older adults, primary care, risk factors for cognitive impairment, time-varying exposure, age-stratified analysis
MeSH terms
Aged, Cognition, Dementia, Female, Humans, Iatrogenic Disease, Male, Thyroid Hormones, Thyrotoxicosis, Thyrotropin, Cohort Studies, Cognitive Dysfunction

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