Double malnutrition and associated factors in a middle-aged and older, rural South African population.

INTRODUCTION: Double malnutrition (co-existing overnutrition and undernutrition) is increasingly prevalent in sub-Saharan Africa due to rapid epidemiological and nutritional transitions. In this region, studies of double malnutrition have largely been conducted at country and household level, with individual-level studies primarily limited to children and women of reproductive age. We investigated the prevalence and determinants of individual-level double malnutrition in middle-aged and older adults who constitute an increasing proportion of the sub-Saharan African population. METHODS: 250 individuals aged 40-70 years (50% women) and resident in the Agincourt Health and socio-Demographic Surveillance System in rural Mpumalanga province, South Africa, were randomly selected. Double malnutrition was defined as overweight/obesity and anaemia only, overweight/obesity and iodine insufficiency, or overweight/obesity and any micronutrient deficiency (anaemia and/or iodine insufficiency). The Chi-squared goodness of fit test was used to compare the expected and observed numbers of individuals with the type of double malnutrition. Logistic regression was used to investigate determinants of each type of double malnutrition. RESULTS: Double malnutrition was present in 22-36% of participants, depending on the definition used. All types of double malnutrition were more common in women than in men (overweight/obesity and anaemia: 34% vs. 10.2%, p < 0.01; overweight/obesity and iodine insufficiency: 32% vs. 12.2%, p < 0.01 and overweight/obesity and any micronutrient deficiency: 50.5% vs. 20.4%, p < 0.01). There were no differences between the overall expected and observed numbers of individuals with combinations of overweight and micronutrient deficiencies [overweight/obesity and anaemia (p = 0.28), overweight/obesity and iodine insufficiency (p = 0.27) or overweight/obesity and any micronutrient deficiency (p = 0.99)]. In models adjusted for socio-demographic factors, HIV and antiretroviral drug status, and food security or dietary diversity, men were 84-85% less likely than women to have overweight/obesity and anaemia, 65% less likely to have overweight/obesity and iodine insufficiency and 74% less likely to have overweight/obesity and any micronutrient deficiency. CONCLUSIONS: Individual-level double malnutrition is prevalent in middle-aged and older adults in a rural sub-Saharan African community. Interventions to improve nutrition in similar settings should target individuals throughout the life course and a focus on women may be warranted.

Misinformation and the Vaccine Adverse Event Reporting System.

This Viewpoint posits that to improve public understanding of the system, the Vaccine Adverse Event Reporting System (VAERS) could use a more accurate name, well-defined guidance about the reporting system's nature and use, and comprehensible information about an event's verification status.

Association of thyroid dysfunction in individuals ≥ 65 years of age with subclinical cardiac abnormalities.

CONTEXT: The relationship between thyroid dysfunction and measures of myocardial disease in older individuals remains to be defined. OBJECTIVE: To evaluate the impact of thyroid dysfunction on structure and function of the left-heart chambers and blood markers of cardiac disease. DESIGN: Cross-sectional analysis. SETTING: The Cardiovascular Health Study, a community-based cohort of older individuals recruited from four urban areas in the United States. PATIENTS: Of 3163 participants studied, 2477 were euthyroid, 465 had subclinical hypothyroidism (SCH), 47 overt hypothyroidism (OH), 45 endogenous (endo) subclinical hyperthyroidism (endo-SCT), and 129 had exogenous (exo) SCT due to thyroid hormone supplementation. INTERVENTIONS: Clinical evaluation, blood sampling and biomarker measurement, 2-dimensional and speckle-tracking echocardiography. MAIN OUTCOME MEASURE(S): Left heart myocardial deformation, circulating biomarkers of diastolic overload (NT-proBNP), fibrosis (sST2, gal-3), and cardiomyocyte injury (hs-cTnT). RESULTS: SCH was associated with higher NT-proBNP (beta = 0.17, p = 0.004), whereas OH was associated with higher hs-cTnT (beta = 0.29, p = 0.005). There were also suggestive associations of SCH with higher sST2, as well as endo-SCT with higher gal-3 and lower (worse) left atrial reservoir strain. Left ventricular longitudinal strain and end-diastolic strain rate did not differ significantly from euthyroid participants in SCH, OH, or exo-SCT. CONCLUSIONS: In this free-living elderly cohort, subclinical and overt hypothyroidism were associated with abnormalities of blood biomarkers consistent with diastolic overload and myocardial necrosis respectively, whereas subclinical hyperthyroidism tended to be associated with myocardial fibrosis and decreased left atrial strain. Our findings could represent stage B heart failure and illuminate distinct aspects of the pathobiology of heart disease related to thyroid gland dysfunction with potential clinical implications.

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Using Natural Language Processing to Extract and Classify Symptoms Among Patients with Thyroid Dysfunction.

In the United States, more than 12% of the population will experience thyroid dysfunction. Patient symptoms often reported with thyroid dysfunction include fatigue and weight change. However, little is understood about the relationship between these symptoms documented in the outpatient setting and ordering patterns for thyroid testing among various patient groups by age and sex. We developed a natural language processing and deep learning pipeline to identify patient-reported outcomes of weight change and fatigue among patients with a thyroid stimulating hormone test. We built upon prior works by comparing 5 open-source, Bidirectional Encoder Representations from Transformers (BERT) to determine which models could accurately identify these symptoms from clinical texts. For both fatigue (f) and weight change (wc), Bio_ClinicalBERT achieved the highest F1-score (f: 0.900; wc: 0.906) compared BERT (f: 0.899; wc: 0.890), DistilBERT (f: 0.852; wc: 0.912), Biomedical RoBERTa (f: 0.864; wc: 0.904), and PubMedBERT (f: 0.882; wc: 0.892).

Strategies to Improve Medical Communication.

This JAMA Insights summarizes strategies for effective medical communication, with considerations for the message delivered, the messenger source, and the social context.

The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

Hormones and Aging: An Endocrine Society Scientific Statement.

Multiple changes occur across various endocrine systems as an individual ages. The understanding of the factors that cause age-related changes and how they should be managed clinically is evolving. This statement reviews the current state of research in the growth hormone, adrenal, ovarian, testicular, and thyroid axes, as well as in osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism, with a specific focus on older individuals. Each section describes the natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, key points, and scientific gaps. The goal of this statement is to inform future research that refines prevention and treatment strategies in age-associated endocrine conditions, with the goal of improving the health of older individuals.

Barriers to and solutions for representative inclusion across the lifespan and in life course research: The need for structural competency highlighted by the COVID-19 pandemic.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating strategies" "Un-Meeting" to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

Subclinical thyroid dysfunction and incident diabetes: a systematic review and an individual participant data analysis of prospective cohort studies.

Objective: Few prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes. Methods: We performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up. Results: Among 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88-1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82-1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87-1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88-1.29). The results were robust in all sub-group and sensitivity analyses. Conclusions: This is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes. Significance statement: Evidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future.

Addressing Online Health Privacy Risks for Older Adults: A Perspective on Ethical Considerations and Recommendations.

The rise in online health information seeking among older adults promises significant benefits but also presents potentially serious privacy risks. In light of these risks, we argue that ongoing research and advocacy aimed at promoting online health information seeking among older adults must be coupled with efforts to identify and address threats to their online privacy. We first detail how internet users reveal sensitive health information to third parties through seemingly innocuous web browsing. We then describe ethical concerns raised by the inadvertent disclosure of health information, which include the potential for dignitary harms, subjective injuries, online health scams, and discrimination. After reviewing ways in which existing privacy laws fail to meet the needs of older adults, we provide recommendations for individual and collective action to protect the online privacy of older adults.

Incorporating Baseline Outcome Data in Individual Participant Data Meta-Analysis of Non-randomized Studies.

Background: In non-randomized studies (NRSs) where a continuous outcome variable (e.g., depressive symptoms) is assessed at baseline and follow-up, it is common to observe imbalance of the baseline values between the treatment/exposure group and control group. This may bias the study and consequently a meta-analysis (MA) estimate. These estimates may differ across statistical methods used to deal with this issue. Analysis of individual participant data (IPD) allows standardization of methods across studies. We aimed to identify methods used in published IPD-MAs of NRSs for continuous outcomes, and to compare different methods to account for baseline values of outcome variables in IPD-MA of NRSs using two empirical examples from the Thyroid Studies Collaboration (TSC). Methods: For the first aim we systematically searched in MEDLINE, EMBASE, and Cochrane from inception to February 2021 to identify published IPD-MAs of NRSs that adjusted for baseline outcome measures in the analysis of continuous outcomes. For the second aim, we applied analysis of covariance (ANCOVA), change score, propensity score and the naïve approach (ignores the baseline outcome data) in IPD-MA from NRSs on the association between subclinical hyperthyroidism and depressive symptoms and renal function. We estimated the study and meta-analytic mean difference (MD) and relative standard error (SE). We used both fixed- and random-effects MA. Results: Ten of 18 (56%) of the included studies used the change score method, seven (39%) studies used ANCOVA and one the propensity score (5%). The study estimates were similar across the methods in studies in which groups were balanced at baseline with regard to outcome variables but differed in studies with baseline imbalance. In our empirical examples, ANCOVA and change score showed study results on the same direction, not the propensity score. In our applications, ANCOVA provided more precise estimates, both at study and meta-analytical level, in comparison to other methods. Heterogeneity was higher when change score was used as outcome, moderate for ANCOVA and null with the propensity score. Conclusion: ANCOVA provided the most precise estimates at both study and meta-analytic level and thus seems preferable in the meta-analysis of IPD from non-randomized studies. For the studies that were well-balanced between groups, change score, and ANCOVA performed similarly.

Evaluation and disposition of older adults presenting to the emergency department with abdominal pain.

BACKGROUND: Abdominal pain is the most common chief complaint in US emergency departments (EDs) among patients over 65, who are at high risk of mortality or incident disability after the ED encounter. We sought to characterize the evaluation, management, and disposition of older adults who present to the ED with abdominal pain. METHODS: We performed a survey-weighted analysis of the National Hospital Ambulatory Medical Care Survey (NHAMCS), comparing older adults with a chief complaint of abdominal pain to those without. Visits from 2013 to 2017 to nationally representative EDs were included. We analyzed 81,509 visits to 1211 US EDs, which projects to 531,780,629 ED visits after survey weighting. We report the diagnostic testing, evaluation, management, additional reasons for visit, and disposition of ED visits. RESULTS: Among older adults (≥65 years), 7% of ED visits were for abdominal pain. Older patients with abdominal pain had a lower probability of being triaged to the "Emergent" (ESI2) acuity on arrival (7.1% vs. 14.8%) yet were more likely to be admitted directly to the operating room than older adults without abdominal pain (3.6% vs. 0.8%), with no statistically significant differences in discharge home, death, or admission to critical care. Ultrasound or CT imaging was performed in 60% of older adults with abdominal pain. A minority (39%) of older patients with abdominal pain received an electrocardiogram (EKG). CONCLUSIONS: Abdominal pain in older adults presenting to EDs is a serious condition yet is triaged to "emergent" acuity at half the rate of other conditions. Opportunities for improving diagnosis and management may exist. Further research is needed to examine whether improved recognition of abdominal pain as a syndromic presentation would improve patient outcomes.

Osteoporosis, Rather Than Sarcopenia, Is the Predominant Musculoskeletal Disease in a Rural South African Community Where Human Immunodeficiency Virus Prevalence Is High: A Cross-Sectional Study.

The rollout of antiretroviral therapy globally has increased life expectancy across Southern Africa, where 20.6 million people now live with human immunodeficiency virus (HIV). We aimed to determine the prevalence of age-related osteoporosis and sarcopenia, and investigate the association between HIV, bone mineral density (BMD), muscle strength and lean mass, and gait speed. A cross-sectional community-based study of individuals aged 20-80 years in rural South Africa collected demographic and clinical data, including HIV status, grip strength, gait speed, body composition, and BMD. Sarcopenia was defined by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) guidelines, and osteoporosis as BMD T-score ≤ -2.5 (if age ≥50 years). The mean ± standard deviation (SD) age of 805 black South African participants was 44.6 ± 14.8 years, 547 (68.2%) were female; 34 (13.2%) were men, and 129 (23.6%) women had HIV, with 88% overall taking anti-retroviral therapy. A femoral neck T-score ≤ -2.5, seen in four of 95 (4.2%) men and 39 of 201 (19.4%) women age ≥50 years, was more common in women with than without HIV (13/35 [37.1%] versus 26/166 [15.7%]; p = 0.003). Although no participant had confirmed sarcopenia, probable sarcopenia affected more men than women (30/258 [11.6%] versus 24/547 [4.4%]; p = .001]. Although appendicular lean mass (ALM)/height2 index was lower in both men and women with HIV, there were no differences in grip strength, gait speed, or probable sarcopenia by HIV status. Older age, female sex, lower ALM/height2 index, slower gait speed, and HIV infection were all independently associated with lower femoral neck BMD. In conclusion, osteoporosis rather than sarcopenia is the common musculoskeletal disease of aging in rural South Africa; older women with HIV may experience greater bone losses than women without HIV. Findings raise concerns over future fracture risk in Southern Africa, where HIV clinics should consider routine bone health assessment, particularly in aging women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Sex Differences in Recovery Across Multiple Domains Among Older Adults With Hip Fracture.

BACKGROUND: Hip fractures are a public health problem among older adults, but most research on recovery after hip fracture has been limited to females. With growing numbers of hip fractures among males, it is important to determine how recovery outcomes may differ between the sexes. METHODS: 168 males and 171 females were enrolled within 15 days of hospitalization with follow-up visits at 2, 6, and 12 months postadmission to assess changes in disability, physical performance, cognition, depressive symptoms, body composition, and strength, and all-cause mortality. Generalized estimating equations examined whether males and females followed identical outcome recovery assessed by the change in each outcome. RESULTS: The mean age at fracture was similar for males (80.4) and females (81.4), and males had more comorbidities (2.5 vs 1.6) than females. Males were significantly more likely to die over 12 months (hazard ratio 2.89, 95% confidence interval: 1.56-5.34). Changes in outcomes were significantly different between males and females for disability, gait speed, and depressive symptoms (p < .05). Both sexes improved from baseline to 6 months for these measures, but only males continued to improve between 6 and 12 months. There were baseline differences for most body composition measures and strength; however, there were no significant differences in change by sex. CONCLUSIONS: Findings confirm that males have higher mortality but suggest that male survivors have continued functional recovery over the 12 months compared to females. Research is needed to determine the underlying causes of these sex differences for developing future prognostic information and rehabilitative interventions.

Changes in the Hierarchy of Functional Impairment From Middle Age to Older Age.

BACKGROUND: Understanding the hierarchy of functional impairment in older adults has helped illuminate mechanisms of impairment and inform interventions, but little is known about whether hierarchies vary by age. We compared the pattern of new-onset impairments in activities of daily living (ADLs) and instrumental ADLs (IADLs) from middle age through older age. METHODS: We conducted a cohort study using nationally representative data from 32 486 individuals enrolled in the Health and Retirement Study. The outcomes were new-onset impairment in each ADL and IADL, defined as self-reported difficulty performing each task, assessed yearly for 9 years. We used multistate models and competing risks survival analysis to estimate the cumulative incidence of impairment in each task by age group (ages 50-64, 65-74, 75-84, and 85 or older). RESULTS: The pattern of incident ADL impairments differed by age group. Among individuals ages 50-64 and 65-74 who were independent at baseline, over 9 years' follow-up, difficulties dressing and transferring were the most common impairments to develop. In individuals ages 75-84 and 85 or older who were independent at baseline, difficulties bathing, dressing, and walking were most common. For IADLs, the pattern of impairments was similar across age groups; difficulty shopping was most common followed by difficulty managing money and preparing meals. Complementary analyses demonstrated a similar pattern. CONCLUSIONS: These findings suggest that the hierarchy of ADL impairment differs by age. These findings have implications for the development of age-specific interventions to prevent or delay functional impairment.

Subclinical hypothyroidism in older individuals.

Subclinical hypothyroidism, which is defined as a thyroid-stimulating hormone concentration higher than the reference range (generally 4·5 mIU/L or higher) with normal free thyroxine concentrations, is frequently found in older individuals. International guidelines differ in recommendations for management of subclinical hypothyroidism in older individuals. We assessed published data during the past decade on the clinical significance and treatment of subclinical hypothyroidism in individuals aged 65 years and older. Meta-analyses, randomised clinical trials, and cohort studies are discussed in this narrative Review. Studies showed no significantly increased incidence in adverse cardiovascular, musculoskeletal, or cognitive outcomes in individuals aged 65 years or older when serum thyroid-stimulating hormone concentration was 4·5-7·0 mIU/L versus a euthyroid group. Moreover, in older individuals with subclinical hypothyroidism, symptoms of hypothyroidism and cardiac and bone parameters did not improve after levothyroxine treatment. These data suggest that treatment with levothyroxine should be considered for individuals aged 65 years or older with subclinical hypothyroidism when thyroid-stimulating hormone concentration is persistently 7 mIU/L or higher and to not initiate treatment with thyroid-stimulating hormone concentrations of less than 7 mIU/L. Levothyroxine doses should be personalised according to age, comorbidities, and life expectancy.