The DOI matches its Crossref record; 32 of the 33 references it cites were found in a registry or an index.
Psychological well‐being in patients on ‘adequate’ doses of l‐thyroxine: results of a large, controlled community‐based questionnaire study
Abstract
Summary: objective Over 1% of the UK population is receiving thyroid hormone replacement with l‐thyroxine (T4). However, many patients complain of persistent lethargy and related symptoms on T4 even with normal TSH levels. To date there has been no large study to determine whether this is related to thyroxine replacement or coincidental psychological morbidity. We have therefore attempted to address this issue using a large, community‐based study. design and patients Computerized prescribing records of five general practices were used to identify 961 patients who had been on thyroxine for a minimum of 4 months from a population of 63 000 (1·5%), along with age‐ and sex‐matched controls. All 1922 individuals were sent a two‐page questionnaire, made up of the short form of the General Health Questionnaire (GHQ‐12), designed to detect minor psychiatric disorders in the community, and a 12‐question ‘thyroid symptom questionnaire’ (TSQ) in the same format. A covering letter explained that we were interested in ‘how patients felt on medication’ and made no direct reference to thyroxine. measurements Scores from the GHQ and TSQ were marked for each individual using the GHQ and Likert scoring methods. Patients’ latest TSH measurements were obtained from laboratory records. Comparisons were then made on scores for the total GHQ‐12, TSQ and individual questions between patients (P) and control (C) groups. Separate analyses were made comparing the patients with a normal TSH (nP) and the control group. results Five hundred and ninety‐seven (62%) of the patients (P) and 551 (57%) of the controls (C) responded and fully completed at least one of the two questionnaire. Three hundred and ninety‐seven responding patients (nP) had a TSH estimation performed in the previous 12 months with the last result being in the local laboratory normal range for TSH (0·1–5·5 or 0·2–6·0 mU/l, according to the assay method used). The responding P, nP and C populations were well matched for age (59·96, 59·73, 59·35 years) and sex (85%, 83%, 87% female). The number of individuals scoring 3 or more on the GHQ‐12 (indicating ‘caseness’) was 21% higher in P than C [185/572 (32·3%) vs. 137/535 (25·6%), P = 0·014] and 26% higher in nP than C [131/381 (34·4%) vs. 137/535 (25·6%), P < 0·005]. Stronger differences were seen with the TSQ scores [C = 187/535 (35·0%), P = 273/583 (46·8%), P < 0·001, P vs. C; and nP = 189/381 (48·6%), P < 0·001, nP vs. C]. Differences existed in chronic drug use and chronic disease prevalence between the control and patient groups, but the differences in GHQ and TSQ scores between the groups remained significant even after correction for these factors as well as age and sex in multiple regression analysis. conclusions This community‐based study is the first evidence to indicate that patients on thyroxine replacement even with a normal TSH display significant impairment in psychological well‐being compared to controls of similar age and sex. In view of the large numbers of people on thyroxine replacement, we believe that these differences, although not large, could contribute to significant psychological morbidity in a substantial number of individuals.
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In the citing paper
“Patients on levothyroxine display ongoing substantial impairment of psychological wellbeing compared with controls of similar age and sex.165”
From Hypothyroidism (2024) · cites this paper as [165]
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 [4]
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 [4]
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 [6]
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 [5]
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 [5]
In the citing paper
“Limiting the analysis to patients with serum TSH in a narrow normal range (0.4-4.0 mU/l) gave similar outcomes: caseness was 35.1% in GHQ-12 and 48.5% in TSQ.”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [11]
In the citing paper
“After correction for age, sex, chronic diseases and chronic medication, the proportion of caseness was higher in patients than in controls, both in the GHQ-12 (34.4 vs. 25.6%,p = 0.012, odds ratio (OR) 1.48 [1.09-2.00])and in the TSQ (48.6 vs. 35.0%,p ! 0.001, OR 1.71 [1.29-2.25]).”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [11]
In the citing paper
“After correction for age, sex, chronic diseases and chronic medication, the proportion of caseness was higher in patients than in controls, both in the GHQ-12 (34.4 vs. 25.6%,p = 0.012, odds ratio (OR) 1.48 [1.09-2.00])and in the TSQ (48.6 vs. 35.0%,p ! 0.001, OR 1.71 [1.29-2.25]).”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [11]
In the citing paper
“The study provided evidence that patients on L-T4 replacement even with a normal serum TSH display significant impairment of psychological well-being compared to controls of similar age and sex.”
From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [11]
In the citing paper
“However, a proportion of individuals continue to suffer with symptoms despite achieving adequate biochemical correction.”
From Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee (2016) · cites this paper as [22]
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).”
In the citing paper
“Hypothyroid subjects on long-term LT4 alone have (a) a 15% excess of psychological caseness (5)”
In the citing paper
“We observed that in individuals on LT4 alone (n = 573), homozygosity for the Thr92Ala polymorphism was associated with reduced QoL (5).”
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Combination Treatment with T4 and T3: Toward Personalized Replacement Therapy in Hypothyroidism?
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“…decrements in general health status, psychological function, and specific cognitive domains (perception, attention, and working memory) in hypothyroid subjects with normal TSH levels compared to euthyroid controls or population norms, despite similar TSH and triiodothyronine (T3) levels (28–30).”
Hypothyroidism in the Elderly: Pathophysiology, Diagnosis and Treatment
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“A clinical trial investigating symptoms found that patients receiving L-thyroxine monotherapy, even with a normal TSH, displayed substantial impairment in psychological well-being compared with controls of similar age and sex (3).”
Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism
Wiersinga, W. M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.258 · Cited by 114
Hypothyroidism and Thyroiditis
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“Three questionnaires for hypothyroid patients have been developed [7–10], but studies evaluating the validity of these measures are still awaited.”
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“Following baseline measurements, the 22 patients with HypoTþPT were included in a randomized controlled trial on replacement therapy with PTH(1-84).”
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Guldvog, I., Reitsma, L. C., Johnsen, L., Lauzike, A., Gibbs, C., Carlsen, E., Lende, T. H., Narvestad, J. K., Omdal, R., Kvaløy, J. T., et al. (2019) · Annals of Internal Medicine · doi:10.7326/m18-0284 · Cited by 99
“Persistent symptoms are thought to be related to autoimmune disease rather than to hypothyroidism (13).”
BackgroundNeuropsychiatric Manifestations of Thyroid Disease
Feldman, A. Z., Shrestha, R. T., & Hennessey, J. V. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.05.005 · Cited by 98
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Wouters, H. J. C. M., van Loon, H. C. M., van der Klauw, M. M., Elderson, M. F., Slagter, S. N., Kobold, A. M., Kema, I. P., Links, T. P., van Vliet-Ostaptchouk, J. V., & Wolffenbuttel, B. H. R. (2017) · Thyroid® · doi:10.1089/thy.2016.0199 · Cited by 97
“Unfortunately, some patients continue to experience symptoms and disturbed well-being despite the fact that they are biochemically euthyroid (3-5).”
McAninch, E. A., Rajan, K. B., Miller, C. H., & Bianco, A. C. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01361 · Cited by 94
“4536 McAninch et al Thyroid Hormone Status in Levothyroxine Therapy J Clin Endocrinol Metab, December 2018, 103(12):4533–4542”
BackgroundInfluentialCarlé, A., Pedersen, I. B., Knudsen, N., Perrild, H., Ovesen, L., & Laurberg, P. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0481 · Cited by 95
Genetic determination of the hypothalamic–pituitary–thyroid axis: where do we stand?
Medici, M., Visser, W. E., Visser, T. J., & Peeters, R. P. (2015) · Endocrine Reviews · doi:10.1210/er.2014-1081 · Cited by 92
“replacement have decreased well-being (15).”
BackgroundCappola, A. R., Desai, A. S., Medici, M., Cooper, L. S., Egan, D., Sopko, G. S., Fishman, G. I., Goldman, S., Cooper, D. S., Mora, S., et al. (2019) · Thyroid · doi:10.1089/thy.2018.0416 · Cited by 95
Levothyroxine Dose Adjustment to Optimise Therapy Throughout a Patient’s Lifetime
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“The existence of residual symptoms in LT4-treated patients was first documented through a patient survey (5) and later through questionnaires that evaluated thyroid-specific symptoms and quality of life (QoL) (6), as well as sophisticated cognitive tests (7).”
BackgroundThvilum, M., Brandt, F., Almind, D., Christensen, K., Brix, T. H., & Hegedüs, L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075789 · Cited by 92
Saravanan, P., Visser, T. J., & Dayan, C. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0414 · Cited by 90
“sectional study (16) and may reflect selection bias in subjects”
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“study confirmed that patients, even with a normal TSH, display significant impairment in psychological well-being, compared with sex- and age-matched controls (1).”
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Optimal thyroid hormone replacement
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Novel insights into thyroid hormones from the study of common genetic variation
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“Large-scale community-based studies have demonstrated impaired well-being in euthyroid patients on LT4 treatment for primary hypothyroidism, indicating that restoration of euthyroidism is not the only predictor of good quality of life in patients with AIT [15,16].”
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Self-citationDesign of New Questionnaires to Measure Quality of Life and Treatment Satisfaction in Hypothyroidism
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“Patients on thyroxine replacement can have significant impairment in psychological well-being compared to controls of similar age and sex (and who had not had throid disease), even though their TSH levels are within the normal laboratory reference range (5).”
Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?
Ettleson, M. D., & Bianco, A. C. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa430 · Cited by 75
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“Furthermore, a proportion of individuals remain symptomatic despite appearing to be biochemically euthyroid.(15) The management of these patients is challenging and often unsatisfactory for patient and clinician alike.”
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“Surprisingly, only few studies evaluating HRQL in thyroid patients have been published [12–19], and a validated disease-specific HRQL-measure is only available for”
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Faasse, K., Cundy, T., & Petrie, K. J. (2009) · BMJ · doi:10.1136/bmj.b5613 · Cited by 72
“Hypothyroid patients, even those taking thyroxine replacement therapy, have been found to have greater levels of emotional distress and more physical symptoms than people without hypothyroidism.”
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Quality of life in patients with primary hypothyroidism related to BMI
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TSH cut off point based on depression in hypothyroid patients
Talaei, A., Rafee, N., Rafei, F., & Chehrei, A. (2017) · BMC Psychiatry · doi:10.1186/s12888-017-1478-9 · Cited by 70
“In hypothyroid patients treated with levothyroxine, psychological symptoms, especially depression, may persist even when they achieve a euthyroid state ([15]).”
BackgroundThe relation between thyroid dysregulation and impaired cognition/behaviour: An integrative review
Eslami‐Amirabadi, M., & Sajjadi, S. A. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12948 · Cited by 80
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Treated hypothyroidism, cognitive function, and depressed mood in old age: the Rancho Bernardo Study
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“Treatment duration was 4 months after optimization of serum TSH levels.”
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“In another study, impaired psychological well-being was found in patients with normal TSH levels during treatment [47].”
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Metadata
- Authors
- Saravanan, P., Chau, W. ‐., Roberts, N., Vedhara, K., Greenwood, R., & Dayan, C. M.
- Affiliations
- Weston General Hospital (GB)
- Bristol Royal Infirmary (GB)
- University of Bristol (GB)
- Corresponding author
- Dayan, C. M.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2002-10-22
- Volume
- 57
- Issue
- 5
- Pages
- 577-585
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W1888479777
- Cited by
- 514
- References
- 33
- Citations by year
- 2026: 12 · 2025: 27 · 2024: 26 · 2023: 30 · 2022: 45 · 2021: 33 · 2020: 37 · 2019: 33 · 2018: 27 · 2017: 26 · 2016: 31 · 2015: 21 · 2014: 25 · 2013: 15 · 2012: 16
- FWCI
- 7.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- 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, thyroid hormone replacement, psychological well-being, thyroid symptoms, thyroid-stimulating hormone, psychiatric morbidity, lethargy, General Health Questionnaire, community-based study, adverse drug reactions, quality of life
- MeSH terms
- Adolescent, Adult, Aged, Drug Administration Schedule, Female, Humans, Hypothyroidism, Male, Middle Aged, Psychiatric Status Rating Scales, Surveys and Questionnaires, Regression Analysis, Thyrotropin, Thyroxine, Chi-Square Distribution, Case-Control Studies
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