The Effects of Levothyroxine Replacement or Suppressive Therapy on Health Status, Mood, and Cognition
Open accessAbstract
CONTEXT: TSH-suppressive doses of levothyroxine (L-T4) have adverse effects on bone and cardiac function, but it is unclear whether central nervous system function is also affected. OBJECTIVE: The aim of the study was to determine whether women receiving TSH-suppressive L-T4 doses have decrements in health status, mood, or cognitive function. DESIGN AND SETTING: A cross-sectional comparison was made among three groups of women in an academic medical center research clinic. PATIENTS: Twenty-four women receiving chronic TSH-suppressive L-T4 doses, 35 women receiving chronic replacement L-T4 doses, and 20 untreated control women participated in the study. INTERVENTIONS: Subjects underwent testing at a single outpatient visit. MAIN OUTCOME MEASURES: We measured health status (SF-36), mood (Profile of Mood States, Symptom Checklist 90-R, Affective Lability Scale), and cognitive function (declarative memory [Paragraph Recall], working memory [N-back, Subject Ordered Pointing], motor learning [Pursuit Rotor, Motor Sequence Learning Test], and executive function [Letter Cancellation Test, Trail Making Test, Iowa Gambling Test]). RESULTS: Women receiving TSH-suppressive or replacement L-T4 doses had decrements in health status and mood compared to healthy controls. These decrements were more pronounced in women receiving replacement, rather than suppressive, L-T4 doses. Memory and executive function were not affected in either treated group, compared to healthy controls. CONCLUSIONS: Women receiving TSH-suppressive doses of L-T4 do not have central nervous system dysfunction due to exogenous subclinical thyrotoxicosis, but TSH-suppressed and L-T4-replaced women have slight decrements in health status and mood that may be related to self-knowledge of the presence of a thyroid condition or other uncharacterized factors. These mood alterations do not impair cognitive function.
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A proportion of individuals have significant dissatisfaction with levothyroxine, including ongoing significant impairment in psychological well-being compared to controls of similar age and sex.
“a proportion of individuals have significant dissatisfaction with it, including ongoing significant impairment in psychological well -being compared to controls of similar age and sex. 4 -8”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [6]
The Results (health status and mood; page not available in our copy) report significantly worse mental-health scores in women receiving levothyroxine than in healthy controls; the groups were matched for age, and all participants were women. The paper does not measure dissatisfaction with levothyroxine or establish what proportion of patients are dissatisfied. Its summary describes the health-status and mood decrements as slight. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPersistent symptoms in patients treated for hypothyroidism are common.
“Persistent symptoms in patients treated for hypothyroidism are common.”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [6]
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- Authors
- Samuels, M. H., Kolobova, I., Smeraglio, A., Peters, D., Janowsky, J. S., & Schuff, K. G.
- Affiliations
- Oregon Health & Science University (US)
- Division of Endocrinology, Diabetes, and Clinical Nutrition (M.H.S., I.K., A.S., K.G.S.), Portland, Oregon 97239
- Division of Biostatistics (D.P.), Portland, Oregon 97239
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-03-01
- Volume
- 99
- Issue
- 3
- Pages
- 843-851
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3942231
- OpenAlex
- W2018940624
- Cited by
- 48
- References
- 34
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 2
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000128)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK075496)
- National Center for Research Resources (UL1 RR 024120, K01RR024120)
- National Center for Advancing Translational Sciences
- 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
- levothyroxine, TSH suppression, thyroid hormone replacement, subclinical hyperthyroidism, mood, health status, cognitive function, executive function, memory, women
- MeSH terms
- Adult, Affect, Cognition, Cross-Sectional Studies, Dose-Response Relationship, Drug, Female, Health Status, Humans, Middle Aged, Thyroid Function Tests, Thyrotropin, Thyroxine, Case-Control Studies, Hormone Replacement Therapy, Young Adult
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 ›
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