Health Status, Psychological Symptoms, Mood, and Cognition in L-Thyroxine-Treated Hypothyroid Subjects

Samuels, Mary H.; Schuff, Kathryn G.; Carlson, Nichole E.; Carello, Phyllis; Janowsky, Jeri S.

doi:10.1089/thy.2006.0252

Cited by 124Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Health Status, Psychological Symptoms, Mood, and Cognition in L-Thyroxine-Treated Hypothyroid Subjects

Samuels, Mary H., Schuff, Kathryn G., Carlson, Nichole E., Carello, Phyllis, Janowsky, Jeri S.·2007·Thyroid

DOI 10.1089/thy.2006.0252

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Abstract

Objective Many hypothyroid subjects receiving L-thyroxine (L-T4) complain of psychological symptoms or cognitive dysfunction. However, there is limited validated information on these self-reports. Design Cross-sectional comparison of 20 euthyroid and 34 treated hypothyroid subjects, aged 20-45 years, with normal thyroid-stimulating hormone (TSH) levels. Subjects underwent the following validated measures: Short Form 36 (SF-36); Symptom Checklist 90-Revised (SCL-90-R); Profile of Mood States (POMS); and tests of declarative memory (Paragraph Recall, Complex Figure), working memory (N-Back, Subject Ordered Pointing, Digit Span Backwards), and motor learning (Pursuit Rotor). Main outcomes L-T4-treated subjects had higher mean TSH and free T4 levels, but free triiodothyronine (T3) levels were comparable to controls. L-T4-treated subjects had decrements on SF-36 and SCL-90-R summary scales and subscales. These subjects performed slightly worse on N-Back and Pursuit Rotor tests. Neither TSH nor thyroid hormone levels were associated with performance on psychological or cognitive measures. Conclusions This group of L-T4-treated subjects had decrements in health status, psychological function, working memory, and motor learning compared to euthyroid controls. Higher mean TSH levels suggest this may be related to suboptimal treatment, although there were no correlations between TSH levels and outcomes. These findings are limited by potential selection bias, and randomized studies targ…

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For some patients, the success of LT4 was limited by persistence of residual cognitive symptoms and decrements in quality of life.
“For some patients, however, the success story was limited by the persistence of residual cognitive symptoms and decrements in the quality of life (5–7).”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [7]
A minority of patients with hypothyroidism remain symptomatic despite normalization of serum thyrotropin levels.
“However, a minority of the patients remain symptomatic despite the normalization of serum thyrotropin levels.”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [7]
In a US study, 34 L-T4-treated subjects had decrements in health status, psychological function, working memory, and motor learning compared to 22 euthyroid controls, with no correlations between serum TSH levels and outcomes.
“In a study from the USA recruiting women mostly by advertisement, 34 L-T4treated subjects had decrements in health status, psychological function, working memory, and motor learning compared to 22 euthyroid controls.There were no correlations between serum TSH levels and outcomes [16] .”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [16]

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Thyroid Disease and Cognition
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Self-citation
Quality of life following lobectomy versus total thyroidectomy is significantly related to hypothyroidism
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Hypothyroidism and Its Rapid Correction Alter Cardiac Remodeling
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Brain Fog in Hypothyroidism: What Is It, How Is It Measured, and What Can Be Done About It
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Self-citation
Thyroid hormone and its metabolites in relation to quality of life in patients treated for differentiated thyroid cancer
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Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life
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“Samuels et al demonstrated no clear association among TSH levels, cognition, and psychological performance while titrating on LT4 monotherapy.(33) For synthetic therapy, a randomized parallel design trial to evaluate FT3 substitution did not show any beneficial effects on psychometric performance, quality of life, and…”
Background
Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study
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Health Status, Mood, and Cognition in Experimentally Induced Subclinical Thyrotoxicosis
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Thyroid hormones are associated with longitudinal cognitive change in an urban adult population
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Thyroid Status, Quality of Life, and Mental Health in Patients on Hemodialysis
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Structural and functional MRI study of the brain, cognition and mood in long-term adequately treated Hashimoto's thyroiditis
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Emerging Therapies in Hypothyroidism
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Chronic Endocrinopathies in Traumatic Brain Injury Disease
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Serum leptin, thyroxine and thyroid-stimulating hormone levels interact to affect cognitive function among US adults: evidence from a large representative survey
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Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats
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Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects
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What Is the Quality of Life in Patients Treated with Levothyroxine for Hypothyroidism and How Are We Measuring It? A Critical, Narrative Review
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The impact of traumatic brain injury on pituitary function
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Endocrine and Metabolic Disorders in Survivors of Childhood Cancers and Health-Related Quality of Life and Physical Activity
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Oral Manifestations of Hypothyroidism: A Case Report
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Resting Energy Expenditure in Obese Women with Primary Hypothyroidism and Appropriate Levothyroxine Replacement Therapy
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Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?
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Experimentally induced subclinical hypothyroidism causes decreased functional connectivity of the cuneus: A resting state fMRI study
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A survey of the young person’s experience of Graves’ disease and its management
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Levothyroxin replacement therapy restores hypothyroidism induced impairment of L-LTP induction: Critical role of CREB
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Thyroid Hormone Transport into Cellular Tissue
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Cognitive Function and Quality of Life in Mild Thyroid Hormone Deficiency
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Does Combination T4 And T3 Therapy Make Sense?
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Effect of thyroxine on synaptotagmin 1 and SNAP-25 expression in dorsal hippocampus of adult-onset hypothyroid rats
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Thyroxine Monotherapy After Thyroidectomy
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Change in Thyroid Hormone Metabolite Concentrations Across Different Thyroid States
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Genetic Difference of Hypothyroidism-Induced Cognitive Dysfunction in C57BL/6j and 129/Sv Mice
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Hipotiroidismo Subclínico no Idoso
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Disease Experience of Patients With Differentiated Thyroid Cancer at Different Phases Based on Timing It Right Framework
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Temporal Pole Responds to Subtle Changes in Local Thyroid Hormone Signaling
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Traumatic Brain Injury
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Health Status, Mood, and Cognition in Experimentally Induced Subclinical Thyrotoxicosis
Samuels, M. H., Schuff, K. G., Carlson, N. E., Carello, P., & Janowsky, J. S. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1957 · Cited by 39 · see citing works
Self-citation
Health Status, Mood, and Cognition in Experimentally Induced Subclinical Hypothyroidism
Samuels, M. H., Schuff, K. G., Carlson, N. E., Carello, P., & Janowsky, J. S. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0011 · Cited by 102 · see citing works
Self-citation
The Effects of Levothyroxine Replacement or Suppressive Therapy on Health Status, Mood, and Cognition
Samuels, M. H., Kolobova, I., Smeraglio, A., Peters, D., Janowsky, J. S., & Schuff, K. G. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3686 · Cited by 48 · see citing works
Self-citation
Neuropsychological functions and metabolic aspects in subclinical hypothyroidism: The effects of l-thyroxine
Baldini, M., Colasanti, A., Orsatti, A., Airaghi, L., Mauri, M. C., & Cappellini, M. D. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.04.009 · Cited by 30 · see citing works
Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects
Samuels, M. H., Kolobova, I., Niederhausen, M., Janowsky, J. S., & Schuff, K. G. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-02668 · Cited by 83 · see citing works
Self-citation

Authors: Samuels, M. H., Schuff, K. G., Carlson, N. E., Carello, P., & Janowsky, J. S.
Affiliations: Oregon Health & Science University (US)
ORCID: Samuels, Mary H.
Carlson, Nichole E.
Venue: Thyroid
Publisher: SAGE Publications
Published: 2007-03
Volume: 17
Issue: 3
Pages: 249-258
ISSN: 1050-7256 (ISSN-L)
1557-9077
DOI: 10.1089/thy.2006.0252
OpenAlex: W2033152833
Cited by: 124
References: 67
Citations by year: 2025: 7 · 2024: 3 · 2023: 9 · 2022: 5 · 2021: 10 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 2 · 2016: 9 · 2015: 8 · 2014: 13 · 2013: 10 · 2012: 6
FWCI: 3.90
Type: journal article
Language: en
Open access: closed
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations: Thyroid (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R21DK062787)
National Center for Research Resources (M01RR00334, M01RR000334)
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: hypothyroidism, levothyroxine, thyroid hormone replacement, psychological symptoms, mood, cognitive function, working memory, motor learning, health status, thyroid-stimulating hormone, free triiodothyronine, young adults
MeSH terms: Adult, Affect, Cognition, Female, Humans, Hypothyroidism, Memory, Middle Aged, Motor Skills, Neuropsychological Tests, Thyroid Gland, Thyroid Hormones, Thyrotropin, Thyroxine, Case-Control Studies

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Health Status, Psychological Symptoms, Mood, and Cognition in L-Thyroxine-Treated Hypothyroid Subjects

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