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Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism
Abstract
Objective: Hypothyroidism is associated with neurocog.nitive impairment. Sparse data suggest that treatment of hypothyroidism, resulting in a return to euthyroidism, may be associated with only partial recovery of overall neurocognitive functioning. The aim of this study was to assess neurocognitive functioning and well-being in euthyroid patients with primary hypothyroidism on adequate thyroxine (T4) treatment. We also investigated whether serum TSH and thyroid antibodies are determinants of neurocognitive functioning and well-being. Design: We assessed neurocognitive functioning and well-being in 141 patients with primary hypothyroidism. Methods: Neurocognitive test results and scores on questionnaires measuring well-being of 141 patients were compared with the reference values for these tests as published and used in Dutch clinical neuropsychological practice. Assessment of neurocognitive functioning included tests for cognitive or psychomotor speed, attention, working memory as well as learning and memory. Well-being was measured with the Symptom Check List-90 total score and the Rand 36-item Health Survey subscales for ‘mental health’ and ‘vitality’. Results: Patients showed poor performance on various domains of neurocognitive functioning compared with mean standard reference values, especially on a complex attention task and on verbal memory tests. Levels of well-being were significantly lower for patients compared with those of the general population. Neither serum TSH nor thyroid antibodies were determinants of neurocognitive functioning and well-being. Conclusion: The results of this study suggest that neurocognitive functioning as well as psychological well-being may not be completely restored in patients with hypothyroidism, despite T4 treatment.
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In the citing paper
“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 [5]
In the citing paper
“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 [5]
In the citing paper
“There is now a consensus that a fraction of the LT4-treated hypothyroid patients with normal serum TSH levels remains symptomatic ( 6 , 7 , 23 , 24 ).”
From Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism (2021) · cites this paper as [7]
In the citing paper
“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 [6]
In the citing paper
“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 [6]
In the citing paper
“Neither serum TSH nor anti-thyroid antibodies were determinants of neurocognitive functioning or well-being.”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [13]
In the citing paper
“Patients showed poor performance on various domains of neurocognitive functioning compared with standard reference values (p = 0.001), especially on a complex attention task and on verbal memory tests.”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [13]
In the citing paper
“Levels of well-being were significantly lower for patients compared with those of the general population (p = 0.001).”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [13]
In the citing paper
“Approximately 10%–15% of subjects with hypothyroidism on L-thyroxine (LT4) alone have persistent symptoms affecting their quality of life (QoL).”
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Metadata
- Authors
- Wekking, E. M., Appelhof, B. C., Fliers, E., Schene, A. H., Huyser, J., Tijssen, J. G. P., & Wiersinga, W. M.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-12
- Volume
- 153
- Issue
- 6
- Pages
- 747-753
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2122267743
- Cited by
- 299
- References
- 20
- Citations by year
- 2026: 4 · 2025: 20 · 2024: 17 · 2023: 17 · 2022: 22 · 2021: 30 · 2020: 16 · 2019: 18 · 2018: 13 · 2017: 21 · 2016: 21 · 2015: 16 · 2014: 16 · 2013: 6 · 2012: 15
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- primary hypothyroidism, thyroxine replacement, euthyroidism, neurocognitive function, psychological well-being, attention, verbal memory, serum TSH, thyroid autoantibodies, SCL-90
- MeSH terms
- Adult, Aged, Antibodies, Attention, Autoimmune Diseases, Cognition, Cognition Disorders, Female, Humans, Hypothyroidism, Iodide Peroxidase, Male, Memory, Mental Health, Middle Aged, Thyroxine, Hormone Replacement Therapy
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