Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism

Wekking, Ellie M; Appelhof, Bente C; Fliers, Eric; Schene, Aart H; Huyser, Jochanan; Tijssen, Jan G P; Wiersinga, Wilmar M

doi:10.1530/eje.1.02025

Cited by 299Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryDementia and Cognitive Impairment Research

Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism

Wekking, Ellie M, Appelhof, Bente C, Fliers, Eric, Schene, Aart H, Huyser, Jochanan, Tijssen, Jan G P, Wiersinga, Wilmar M·2005·European Journal of Endocrinology

DOI 10.1530/eje.1.02025

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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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Persistent 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 [5]
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 [5]
A fraction of LT4-treated hypothyroid patients with normal serum TSH levels remains symptomatic.
“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]
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 [6]
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 [6]

In the Dutch study, neither serum TSH nor anti-thyroid antibodies were determinants of neurocognitive functioning or well-being.
“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 a Dutch community-based study, 141 L-T4-treated patients with autoimmune hypothyroidism and serum TSH 0.11-4.0 mU/l showed poor performance on various domains of neurocognitive functioning compared with Dutch general population reference values (p = 0.001), especially on a complex attention task and verbal memory tests.
“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 same Dutch study, levels of well-being were significantly lower for patients compared with the general population (p = 0.001).
“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]
Approximately 10%-15% of subjects with hypothyroidism on L-thyroxine (LT4) alone have persistent symptoms affecting their quality of life (QoL).
“Approximately 10%–15% of subjects with hypothyroidism on L-thyroxine (LT4) alone have persistent symptoms affecting their quality of life (QoL).”
From Designing a combined liothyronine (LT3), L- thyroxine (LT4) trial in symptomatic hypothyroid subjects on LT4 - the importance of patient selection, choice of LT3 and trial design (2023) · cites this paper as [4]

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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)
ORCID: Wekking, Ellie M
Fliers, Eric
Schene, Aart H
Tijssen, Jan G P
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
DOI: 10.1530/eje.1.02025
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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Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism

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