Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects

Samuels, Mary H.; Kolobova, Irina; Niederhausen, Meike; Janowsky, Jeri S.; Schuff, Kathryn G.

doi:10.1210/jc.2017-02668

Cited by 67 publications

(51 citation statements)

References 31 publications

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“…A limitation of the present study is that changes in plasma TSH within the reference range following the switch are not addressed. However, TSH changes within the reference range following a small dose change are unlikely to result in changes in hypothyroid symptoms, well-being, or quality of life (10,11).Furthermore, in the Nivel-PCD prescriptions from the GPs, no actual dispensing data are known, while the reverse is true for PHARMO. Therefore some patients might have a prescription which they did not collect at the pharmacy.…”

Section: Discussionmentioning

confidence: 99%

Impact of a Forced Dose-Equivalent Levothyroxine Brand Switch on Plasma Thyrotropin: A Cohort Study

Flinterman

Kuiper

Korevaar

et al. 2020

Thyroid

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Section: Discussionmentioning

confidence: 99%

Impact of a Forced Dose-Equivalent Levothyroxine Brand Switch on Plasma Thyrotropin: A Cohort Study

Flinterman

Kuiper

Korevaar

et al. 2020

Thyroid

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“…However, another possibility is that many symptoms are not due to the abnormal thyroid hormone status caused by HT but are directly attributable to the autoimmune condition itself. This is supported by many well-controlled studies in which adjustment of levothyroxine or use of alternative thyroid hormone therapies has not proven efficacious (2,3). Data indicate that TPOAb may cross-react with tissues other than the thyroid and may contribute to inflammation and systemic symptoms.…”

Section: Summary Backgroundmentioning

confidence: 97%

Thyroidectomy Improves Quality of Life and Fatigue in Patients with Hashimoto's Disease and Persistent Symptoms Compared to Adequate Thyroid Hormone Replacement

AngellTrevor

2019

Clinical Thyroidology

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“…The expression of dissatisfaction may be partly explained by raised awareness of the problem, based on unspecific subjective criteria, and the possible contribution of a lack in certainty of the diagnostic process discussed above [11, 29–45]. Patient expectations introduce a confounding influence on perceived outcomes [11, 53, 54]. This is difficult to address, particularly since expectation bias extends to RCTs, regarded as the highest class of evidence in Evidenced-Based Medicine [53].…”

Section: Main Textmentioning

confidence: 99%

“…A thyroid-specific QoL has only recently been developed and validated [51]. Simpson’s paradox (also known as amalgamation bias or collider stratification bias) may explain, at least in part, why otherwise well-performed studies failed to provide a convincing relationship between symptoms and thyroid function tests [27, 54, 59–61]. The paradox is a relevant factor for the relationship of patient complaints, biochemical markers and treatment response to LT4 [60].…”

Section: Main Textmentioning

confidence: 99%

Time for a reassessment of the treatment of hypothyroidism

Midgley

Toft²,

Larisch³

et al. 2019

BMC Endocr Disord

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Background In the treatment for hypothyroidism, a historically symptom-orientated approach has given way to reliance on a single biochemical parameter, thyroid stimulating hormone (TSH). Main body The historical developments and motivation leading to that decision and its potential implications are explored from pathophysiological, clinical and statistical viewpoints. An increasing frequency of hypothyroid-like complaints is noted in patients in the wake of this directional shift, together with relaxation of treatment targets. Recent prospective and retrospective studies suggested a changing pattern in patient complaints associated with recent guideline-led low-dose policies. A resulting dramatic rise has ensued in patients, expressing in various ways dissatisfaction with the standard treatment. Contributing factors may include raised problem awareness, overlap of thyroid-related complaints with numerous non-specific symptoms, and apparent deficiencies in the diagnostic process itself. Assuming that maintaining TSH anywhere within its broad reference limits may achieve a satisfactory outcome is challenged. The interrelationship between TSH, free thyroxine (FT4) and free triiodothyronine (FT3) is patient specific and highly individual. Population-based statistical analysis is therefore subject to amalgamation problems (Simpson’s paradox, collider stratification bias). This invalidates group-averaged and range-bound approaches, rather demanding a subject-related statistical approach. Randomised clinical trial (RCT) outcomes may be equally distorted by intra-class clustering. Analytical distinction between an averaged versus typical outcome becomes clinically relevant, because doctors and patients are more interested in the latter. It follows that population-based diagnostic cut-offs for TSH may not be an appropriate treatment target. Studies relating TSH and thyroid hormone concentrations to adverse effects such as osteoporosis and atrial fibrillation invite similar caveats, as measuring TSH within the euthyroid range cannot substitute for FT4 and FT3 concentrations in the risk assessment. Direct markers of thyroid tissue effects and thyroid-specific quality of life instruments are required, but need methodological improvement. Conclusion It appears that we are witnessing a consequential historic shift in the treatment of thyroid disease, driven by over-reliance on a single laboratory parameter TSH. The focus on biochemistry rather than patient symptom relief should be re-assessed. A joint consideration together with a more personalized approach may be required to address the recent surge in patient complaint rates.

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Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects

Cited by 67 publications

References 31 publications

Impact of a Forced Dose-Equivalent Levothyroxine Brand Switch on Plasma Thyrotropin: A Cohort Study

Impact of a Forced Dose-Equivalent Levothyroxine Brand Switch on Plasma Thyrotropin: A Cohort Study

Thyroidectomy Improves Quality of Life and Fatigue in Patients with Hashimoto's Disease and Persistent Symptoms Compared to Adequate Thyroid Hormone Replacement

Time for a reassessment of the treatment of hypothyroidism

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