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Department of Endocrinology, Gateshead Health NHS Foundation Trust, Gateshead, United Kingdom
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Department of Endocrinology, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
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Department of Endocrinology, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
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Introduction: Serum thyroid-stimulating hormone (TSH) increases with age but target TSH is similar in younger and older hypothyroid patients on treatment. It is unknown if quality of life (QoL), hypothyroid symptoms and cardiovascular risk factors change in older hypothyroid patients treated to an age-appropriate reference range. Objective: To assess if a higher target serum TSH of 4.01–8.0 mU/L is feasible in, and acceptable to, older treated hypothyroid patients. Methods: A single-blind (participant) randomised controlled feasibility trial involving 48 hypothyroid patients aged ≥80 years on established and stable levothyroxine (LT4) therapy with serum TSH levels within the standard reference range (0.4–4.0 mU/L) was conducted. Standard (0.4–4.0 mU/L) or higher (4.1–8.0 mU/L) TSH target (standard TSH [ST] or higher TSH [HT] groups) LT4 for 24 weeks was administered. The outcome measures evaluated were thyroid function tests, QoL, hypothyroid symptoms, cardiovascular risk factors and serum marker of bone resorption in participants that completed the trial (n = 21/24 ST group, n = 19/24 HT group). Results: At 24 weeks, in the ST and HT groups, respectively, median (interquartile range) serum TSH was 1.25 (0.76–1.72) and 5.50 (4.05–9.12) mU/L, mean (± SD) free thyroxine (FT4) was 19.4 ± 3.5 and 15.9 ± 2.4 pmol/L, and daily LT4 dose was 82.1 ± 26.4 and 59.2 ± 23.9 µg. There was no suggestion of adverse impact of a higher serum TSH in the HT group with regard to any of the outcomes assessed. Conclusions: In hypothyroid patients aged ≥80 years on LT4 therapy for 24 weeks, there was no evidence that a higher target serum TSH was associated with an adverse impact on patient reported outcomes, cardiovascular risk factors or bone resorption marker over 24 weeks. Longer-term trials assessing morbidity and mortality outcomes and health-utility in this age group are feasible and should be performed.
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Background: International societies have recommended that levothyroxine should not routinely be prescribed in older individuals for the management of mild subclinical hypothyroidism (SCH). However, it is unknown whether clinicians managing people with SCH are either aware of or adhere to these guidelines. Methods: A web-based survey of members of several international thyroid associations and general practitioners in North-East England was conducted. Respondents were presented with a vignette of an 80-year-old gentleman with mild persistent SCH experiencing tiredness. Multivariable logistic regression analyses were performed to evaluate predictors of awareness of guidelines and responses to treatment. Results: The survey response rate was 21.9% (565/2,583). Only 7.6% of clinicians were unaware of guidelines regarding management of SCH in older people. Twenty percent of clinicians stated that they would treat the older patient with mild SCH, whereas 13% were unsure. Clinicians from North America were more likely to treat the older person with mild SCH than clinicians from elsewhere (OR 2.24 [1.25–3.98]). Likewise, non-endocrinologists were also more likely than endocrinologists to treat the older person with mild SCH (OR 3.26 [1.45–6.47]). Conclusion: The majority of clinicians are aware of guidelines regarding management of SCH in older individuals. However, a considerable proportion of clinicians would still treat an older person with non-specific symptoms and mild SCH. These guidelines need to be disseminated more widely and more research is required to understand barriers to adherence to international recommendations.
Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Queen Elizabeth Hospital, Gateshead, UK
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Subclinical hypothyroidism (SCH) should be considered in two categories according to the elevation in serum thyroid-stimulating hormone (TSH) level: mildly increased TSH levels (4.0-10.0 mU/l) and more severely increased TSH value (>10 mU/l). An initially raised serum TSH, with FT<sub>4</sub> within reference range, should be investigated with a repeat measurement of both serum TSH and FT<sub>4</sub>, along with thyroid peroxidase antibodies, preferably after a 2- to 3-month interval. Even in the absence of symptoms, replacement therapy with <smlcap>L</smlcap>-thyroxine is recommended for younger patients (<65-70 years) with serum TSH >10 mU/l. In younger SCH patients (serum TSH <10 mU/l) with symptoms suggestive of hypothyroidism, a trial of <smlcap>L</smlcap>-thyroxine replacement therapy should be considered. For such patients who have been started on <smlcap>L</smlcap>-thyroxine for symptoms attributed to SCH, response to treatment should be reviewed 3 or 4 months after a serum TSH within reference range is reached. If there is no improvement in symptoms, <smlcap>L</smlcap>-thyroxine therapy should generally be stopped. Age-specific local reference ranges for serum TSH should be considered in order to establish a diagnosis of SCH in older people. The oldest old subjects (>80-85 years) with elevated serum TSH ≤10 mU/l should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. If the decision is to treat SCH, then oral <smlcap>L</smlcap>-thyroxine, administered daily, is the treatment of choice. The serum TSH should be re-checked 2 months after starting <smlcap>L</smlcap>-thyroxine therapy, and dosage adjustments made accordingly. The aim for most adults should be to reach a stable serum TSH in the lower half of the reference range (0.4-2.5 mU/l). Once patients with SCH are commenced on <smlcap>L</smlcap>-thyroxine treatment, then serum TSH should be monitored at least annually thereafter.
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Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Queen Elizabeth Hospital, Gateshead, UK
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Department of Endocrinology, Gateshead Health NHS Foundation Trust, Gateshead, UK
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Department of Cardiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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Department of Cardiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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Objectives
To study the relationship between serum-free T3 (FT3), C-reactive protein (CRP) and all-cause mortality in patients with acute myocardial infarction (AMI).
Design
Prospective multicentre longitudinal cohort study.
Methods
Between December 2014 and December 2016, thyroid function and CRP were analysed in AMI (both ST-elevation (STEMI) and non-ST-elevation) patients from the Thyroxine in Acute Myocardial Infarction study. The relationship of FT3 and CRP at baseline with all-cause mortality up to June 2020 was assessed. Mediation analysis was performed to evaluate if CRP mediated the relationship between FT3 and mortality.
Results
In 1919 AMI patients (29.2% women, mean (s.d.) age: 64.2 (12.1) years and 48.7% STEMI) followed over a median (interquartile range) period of 51 (46–58) months, there were 277 (14.4%) deaths. Overall, lower serum FT3 and higher CRP levels were associated with higher risk of mortality. When divided the patients into tertiles based on the levels of FT3 and CRP; the group with the lowest FT3 and highest CRP levels had a 2.5-fold increase in mortality risk (adjusted hazard ratio (95% CI) of 2.48 (1.82–3.16)) compared to the group with the highest FT3 and lowest CRP values. CRP mediated 9.8% (95% CI: 6.1–15.0%) of the relationship between FT3 and mortality.
Conclusions
In AMI patients, lower serum FT3 levels on admission are associated with a higher mortality risk, which is partly mediated by inflammation. Adequately designed trials to explore the potential benefits of T3 in AMI patients are required.
