Subclinical Hypothyroidism In Older Adults Research Articles

Patient-Reported Satisfaction with Thyroid Hormone Replacement Therapy for Subclinical Hypothyroidism in Older Adults: A Pooled Analysis of Individual Participant Data from Two Randomized Controlled Trials.

Background: The benefit of levothyroxine treatment of subclinical hypothyroidism (SCH) is subject to debate. This study compared treatment satisfaction between older adults with SCH using levothyroxine or placebo. Methods: We analyzed pooled individual participant data from two randomized, double-blind, placebo-controlled trials investigating the effects of levothyroxine treatment in older adults with SCH. Community-dwelling participants aged ≥65 years, with SCH (persistent thyrotropin levels 4.60-19.99 mIU/L for >3 months and normal free T4 level), were included. Intervention dose titration until thyrotropin levels normalized, with a mock dose adjustment of placebo. Treatment satisfaction was determined during the final study visit using the Treatment Satisfaction Questionnaire for Medication (TSQM), encompassing perceived effectiveness, side effects, convenience, and global satisfaction, along with the participants' desire to continue study medication after the trial. Results: We included 536 participants. At baseline, the median (interquartile range [IQR]) age was 74.9 (69.7-81.4) years, and 292 (55%) were women. The median (IQR) thyrotropin levels were 5.80 (5.10-7.00) mIU/L at baseline in both groups; at final visit, 4.97 (3.90-6.35) mIU/L in the placebo and 3.24 (2.49-4.41) mIU/L in the levothyroxine group. After treatment, the groups did not differ significantly in global satisfaction (mean difference [CI] -1.1 [-4.5 to 2.1], p = 0.48), nor in any other domain of treatment satisfaction. These results held true regardless of baseline thyrotropin levels or symptom burden. No major differences were found in the numbers of participants who wished to continue medication after the trial (levothyroxine 35% vs. placebo 27%), did not wish to continue (levothyroxine 27% vs. placebo 30%), or did not know (levothyroxine 37% vs. placebo 42%) (p = 0.14). In a subpopulation with high symptom burden from hypothyroid symptoms at baseline, those using levothyroxine more often desired to continue the medication after the trial than those using placebo (mean difference [CI]: -21.1% [-35.6% to -6.5%]). Conclusion: These pooled data from two RCTs showed no major differences in treatment satisfaction between older adults receiving levothyroxine or placebo. This finding has important implications for decision-making regarding initiating levothyroxine treatment for SCH. Our findings generally support refraining from routinely prescribing levothyroxine in older adults with SCH.

The Rational Use of Hormone Replacement Therapy in Older Adults

Multiple hormone levels are lower in older compared to younger adults, but the clinical implications are controversial. Lower thyroid hormone, testosterone, estrogen and vitamin D are variously associated with metabolic syndrome, sarcopenia, low bone density and cognitive decline, for which treatment has been recommended in the past. However, evidence from the T Trials of testosterone therapy failed to show benefit for endpoints other than sexual function. In the Women’s Health Initiative, a large RCT of estrogen replacement in older women, found evidence of an interaction between estrogen therapy and metabolic risk factors such as diabetes that actually exacerbates risk of cognitive decline. Longitudinal observation of thyroid hormone and thyrotropin patterns in the Baltimore Longitudinal Study of Aging demonstrate heterogeneity that might account for a lack of benefit in studies of treatment for subclinical hypothyroidism in older adults. At the same time, new data suggest the need for a more aggressive threshold for vitamin D in older adults, with a lower threshold associated with a drop in physical function compared to younger adults. Complexity in the regulation of hormonal pathways and the downstream effects on target tissues means multiple individuals with similar hormone levels may have different underlying physiology, with divergent clinical needs. Changes in activity and diet common during aging, and exacerbated by the pandemic, lead to physical and mood changes associated with hormonal dysfunction in popular culture and patient requests for evaluation. The ultimate goal should be personalized treatment decisions based on comprehensive evaluation and pathophysiology.

T3:T4 Ratio Can Distinguish Between Adaptive Changes and True Subclinical Hypothyroidism in Older Adults

Because of heterogeneity in hormonal aging,1 we believe isolated elevated TSH is insufficient to drive clinical decision making for thyroid hormone replacement in older adults. We performed a cross-sectional study involving 63 older adult participants of the BLSA in order to assess the diagnostic value of individual hormone levels or free T3: free T4 ratio for differentiating thyroid-aging phenotypes. We defined two phenotypic groups, central adaptation and primary hypothyroidism, both with a rising TSH and with a rising or falling FT4 respectively. Fifty-four percent of study participants were male, the average age was 78.8 years, and 66.7% had the primary hypothyroidism phenotype. The unadjusted odds ratio of having the central adaptation phenotype is 23.40 (95% CI 3.66-149.73) for every unit increase in the FT3:FT4 ratio. The ROC curve had a C-statistic of 0.815. Similarly, FT4 alone distinguished the phenotypes with a C-statistic of 0.864. In contrast, TSH and FT3 were not predictive (C-statistic of 0.617, and 0.479 respectively). When the analysis is limited to the 24 individuals with elevated TSH, the ratio remains predictive (0.839). Both the higher FT4 and the lower ratio found in individuals with adaptive changes are consistent with a physiology similar to the adaptations seen in acute illness. This supports the hypothesis that elevated TSH can represent a response to stressors with aging and doesn’t always warrant treatment with thyroid hormone. Our findings suggest that full thyroid function panel can be used to make better diagnostic decisions in older adults.

Skeletal Effects of Levothyroxine for Subclinical Hypothyroidism in Older Adults: A TRUST Randomized Trial Nested Study.

Both thyroid dysfunction and levothyroxine (LT4) therapy have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results. To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo. Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration versus placebo with computerized mock titration. 196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment. One-year percentage changes of BMD, TBS, and 2 serum BTMs (serum CTX-1 [sCTX] and procollagen type 1 N-terminal polypeptide [P1NP]). Student's t-test for unadjusted analyses and linear regression adjusted for clinical center and sex were performed. Mean age was 74.3 years ± 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (-0.6%; between-groups difference +1.4%: 95% confidence interval [CI] -0.1 to 2.9, P = .059). Likewise, there were no between-group differences in 1-year change in TBS (-1.3%: 95% CI -3.1 to 0.6, P = .19), total hip BMD (-0.2%: 95% CI -1.1 to 0.1, P = .61), or BTMs levels (sCTX +24.1%: 95% CI -7.9 to 56.2, P = .14), or after adjustment for clinical centers and sex. Over 1-year levothyroxine had no effect on bone health in older adults with SHypo. ClinicalTrial.gov NCT01660126 and NCT02491008.

Unstable Thyroid Function in Older Adults Is Caused by Alterations in Both Thyroid and Pituitary Physiology and Is Associated with Increased Mortality

Average thyrotropin (TSH) levels are known to be higher in older adults when measured in cross-sectional populations. Possible etiologies include differential survival, neutral aging changes, or increased disease prevalence at older ages. This study aimed to elucidate the mechanisms underlying changing thyroid function during aging, and to determine the association of changes with survival, by analyzing the individual thyroid axis over time. Individual patterns of changing TSH and free thyroxine (fT4) were determined in 640 participants in the Baltimore Longitudinal Study of Aging who had at least three measures of serum TSH and fT4, not on medications, over an average of seven years of follow-up. Participants with changing phenotypes were identified based on quintiles for both slopes. Those with alterations in primary thyroid gland function demonstrated intact negative feedback (rising TSH with declining fT4 or declining TSH with rising fT4). Other participants had a parallel rise or fall of TSH and fT4 levels, consistent with pituitary dysfunction. Predictors of phenotype were analyzed by logistic regression. Differential survival between thyroid aging phenotypes was analyzed using multivariate Cox regression. While the majority of participants at all ages had stable thyroid function, changes were more common among older adults, with 32.3% of those aged >80 years but only 9.5% of those aged <60 years demonstrating thyroid function changes in the highest and lowest quintiles. Regression to the mean accounts for some of the changes, for example increased baseline TSH was associated with a falling TSH pattern (odds ratio = 1.4 [confidence interval 1.1-1.7] per 1 mIU/L). Importantly, changing thyroid function in either the upper or lower quintiles of slope for TSH and fT4 was associated with increased risk of death compared to stable thyroid status (hazard ratio = 5.4 [confidence interval 3.1-9.5]). Changing thyroid hormone function is increasingly common at older ages and is associated with decreased survival. Nonetheless, the tendency for abnormal thyroid function tests to resolve, along with altered pituitary responsiveness underlying some TSH elevations, suggests that an elevated TSH level should be not assumed to represent subclinical hypothyroidism in older adults. Thus, caution is appropriate when determining the need for thyroid hormone supplements in older adults.

Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults

As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We found no association between treatment rate and other physician characteristics. GPs were more reluctant to initiate treatment in 85-year-old than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). There are strong variations in treatment strategies for elderly patients with subclinical hypothyroidism across different Swiss regions, including use of higher starting doses than the recommended 25 µg in the Swiss guidelines, which recommend a starting dose of 25 µg. These variations likely reflect the current uncertainty about the benefits of treatment, which arise from the current lack of evidence from adequately powered clinical trials.

International variation in GP treatment strategies for subclinical hypothyroidism in older adults: a case-based survey.

There is limited evidence about the impact of treatment for subclinical hypothyroidism, especially among older people. To investigate the variation in GP treatment strategies for older patients with subclinical hypothyroidism depending on country and patient characteristics. Case-based survey of GPs in the Netherlands, Germany, England, Ireland, Switzerland, and New Zealand. The treatment strategy of GPs (treatment yes/no, starting-dose thyroxine) was assessed for eight cases presenting a woman with subclinical hypothyroidism. The cases differed in the patient characteristics of age (70 versus 85 years), vitality status (vital versus vulnerable), and thyroid-stimulating hormone (TSH) concentration (6 versus 15 mU/L). A total of 526 GPs participated (the Netherlands n = 129, Germany n = 61, England n = 22, Ireland n = 21, Switzerland n = 262, New Zealand n = 31; overall response 19%). Across countries, differences in treatment strategy were observed. GPs from the Netherlands (mean treatment percentage 34%), England (40%), and New Zealand (39%) were less inclined to start treatment than GPs in Germany (73%), Ireland (62%), and Switzerland (52%) (P = 0.05). Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old females (pooled odds ratio [OR] 0.74 [95% confidence interval [CI] = 0.63 to 0.87]). Females with a TSH of 15 mU/L were more likely to get treated than those with a TSH of 6 mU/L (pooled OR 9.49 [95% CI = 5.81 to 15.5]). GP treatment strategies of older people with subclinical hypothyroidism vary largely by country and patient characteristics. This variation underlines the need for a new generation of international guidelines based on the outcomes of randomised clinical trials set within primary care.

Thyroid status and functional and cognitive status at baseline and survival after 3 years of follow-up: the OCTABAIX study

Subclinical thyroid disorders are common in older individuals. Health risks associated with subclinical hypothyroidism in older adults are unclear. The aim of the study is to evaluate whether thyroid status in elderly subjects correlates with physical and cognitive function at baseline and with 3-year mortality. A population-based, prospective cohort of the OCTABAIX study (307 inhabitants aged 85 years at baseline). Chronic drug prescription, functional status (Barthel and Lawton indices) and cognitive status according to the Spanish version of the Mini-Mental State Examination were recorded. Quality of life was assessed using the visual analogue scale of the quality of life test. Concentrations of TSH and thyroxine were measured. Participants were classified in accordance with clinical categories of thyroid function. Twenty (6.5%) individuals had subclinical hypothyroidism and five (1.6%) had subclinical hyperthyroidism. Compared with euthyroid subjects (n=280; 91.8%), subclinical hypo- and hyperthyroidism subjects were not significantly associated with poor physical or cognitive function at baseline. Fifty-one (15.1%) subjects died during the 36 months of follow-up. TSH values and subclinical hypo- and hyperthyroidism were not associated with an increased overall mortality risk (hazard ratio (HR) 1.086, 95% CI 0.987-1.196 and HR 0.905, 95% CI 0.902-1.053 respectively). This study does not support the association of TSH or thyroid disorders with physical or cognitive function at baseline or with 3-year mortality in the oldest old subjects.

International variation in GP treatment strategies for subclinical hypothyroidism in older adults

International variation in GP treatment strategies for subclinical hypothyroidism in older adults

Natural History of Subclinical Hypothyroidism in Older Adults

Because thyroid testing is performed widely in older adults, clinicians often encounter cases of subclinical hypothyroidism (i.e., elevated serum

Subclinical Hypothyroidism and Functional Mobility in Older Adults

Health risks associated with subclinical hypothyroidism in older adults are unclear. Our objective was to compare the functional mobility of people aged 70 to 79 years by thyroid function categorized by thyrotropin (TSH) level as euthyroid (>or=0.4 to <4.5 mIU/L), mild subclinical hypothyroid (>or=4.5 to <7.0 mIU/L), or moderate subclinical hypothyroid (>or=7.0 to <or=20.0 mIU/L with a normal free thyroxine level) cross-sectionally and over 2 years. A total of 2290 community-dwelling residents participating in the year 2 clinic visit (July 1998-June 1999) of the Health, Aging, and Body Composition (Health ABC) Study, who had measured TSH level, had the capacity to walk 20 m unaided, and were not taking thyroid medication or had TSH levels consistent with hyperthyroidism or hypothyroidism. Main outcome measures included self-reported and performance-based measures of mobility (usual and rapid gait speed and endurance walking ability) assessed at study baseline (year 2) and 2 years later. In age- and sex-adjusted analyses, the mild subclinical hypothyroid group (vs the euthyroid group) demonstrated better mobility (faster mean usual and rapid gait speed [1.20 vs 1.15 m/s and 1.65 vs 1.56 m/s, respectively; P < .001] and had a higher percentage of those with good cardiorespiratory fitness and reported walking ease [39.2% vs 28.0% and 44.7% vs 36.5%, respectively; P < .001]). After 2 years, persons with mild subclinical hypothyroidism experienced a similar decline as the euthyroid group but maintained their mobility advantage. Persons with moderate subclinical hypothyroidism had similar mobility and mobility decline as the euthyroid group. Generally, well-functioning 70- to 79-year-old individuals with subclinical hypothyroidism do not demonstrate increased risk of mobility problems, and those with mild elevations in TSH level show a slight functional advantage.