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.

Is Season of Diagnosis a Predictor of Cancer Survival? Results from the Zurich Cancer Registry.

In Switzerland, there is a large seasonal variation in sunlight, and vitamin D deficiency is relatively common during winter. The season of diagnosis may be linked to cancer survival via vitamin D status. Using data from the Cancer Registry of Zurich, Zug, Schaffhausen, and Schwyz with more than 171,000 cancer cases registered since 1980, we examined the association of the season of diagnosis with survival for cancers including prostate (ICD10 code C61; International Categorization of Diseases, version 10), breast (C50), colorectal (C18-21), lung (C34), melanoma (C43), and all sites combined. Cox proportional hazards regression models were used to assess the differences in the all-cause mortality by the season of the diagnosis. Winter was used as the reference season. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for all the cancers combined (excluding nonmelanoma skin cancer) and for prostate (in men), breast (in women), colorectal, lung cancer, and melanomas, separately. A diagnosis in summer and/or autumn was associated with improved survival in all the sites combined for both sexes (men: HR 0.97 [95% CI 0.96-0.99]; women: HR 0.97 [95% CI 0.94-0.99]) and in colorectal (HR 0.91 [95% CI 0.84-0.99]), melanoma (HR 0.81 [95% CI 0.65-1.00]), and breast cancer (HR 0.91 [95% CI 0.94-0.99]) in women. Our study results suggest that a cancer diagnosis in summer and/or autumn is associated with a better prognosis. The improved seasonal survival coincides with the seasonal variation of sun-induced vitamin D, and vitamin D may play a protective and beneficial role in cancer survival.

Parathyroid Hormone in Pregnancy: Vitamin D and Other Determinants.

We aimed to assess the parathyroid hormone (PTH) concentration in pregnant women at the beginning of pregnancy (1st trimester) and within days before delivery (3rd trimester) and evaluate its determinants. From September 2014 through December 2015 in a cross-sectional study, 204 women in the 1st trimester of pregnancy and 203 women in the 3rd trimester of pregnancy were recruited. Blood samples were collected to measure PTH and circulating 25-hydroxy-vitamin D (25(OH)D) concentrations. Lifestyle and demographic data were collected using a questionnaire. Serum 25(OH)D and PTH were inversely correlated in both early and late pregnancy. Our analyses suggest that in the 3rd trimester of pregnancy, a 25(OH)D level of 18.9 ng/mL (47.3 nmol/L) could serve as an inflection point for the maximal suppression of PTH. Statistically significant determinants of PTH concentrations in multiple regression were 25(OH)D concentrations, season, multiparity and education of the partner (all p < 0.05) in early pregnancy. In late pregnancy, 25(OH)D concentrations and country of origin were statistically significant determinants of PTH concentrations (all p < 0.05). These factors and their effect on PTH appear to be vastly determined by 25(OH)D; however, they might also affect PTH through other mechanisms besides 25(OH)D.

Body weight and self-perception are associated with depression: Results from the National Health and Nutrition Examination Survey (NHANES) 2005-2016.

BACKGROUND: Despite evidence suggesting that perceptual body image measurements are strongly associated with depression, few studies examined the association between perceptual body image and depression in adults. This study aimed to investigate the association of different measures of perceptual body image measurements with depression. METHODS: We analyzed data of 22,735 adults participating in the National Health and Nutrition Examination Survey between 2005 and 2016. Depression was ascertained using the validated Patient Health Questionnaire (PHQ-9) and depression was defined as PHQ score ≥10. The associations of measured body mass index (BMI) and body image (i.e., self-reported BMI, BMI discordance, perceived weight, and desired weight) with depression were assessed using logistic regression. RESULTS: Women perceiving themselves as overweight or reporting their BMI as obese had significantly higher odds of depression (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.17-1.72 and 1.29, 1.04-1.60, respectively) compared to women perceiving themselves as about the right weight or reporting their BMI as normal. The association between perceived overweight and depression was independent of measured BMI (OR 1.37, 95% CI 1.09-1.72). Men perceiving themselves as underweight had higher odds of depression (OR 1.50, 95% CI 1.06-2.11) than men perceiving themselves as about the right weight. In women, but not in men, measured obesity was associated with higher odds of depression. LIMITATIONS: The study's cross-sectional design and missing information on comorbidities. CONCLUSION: Weight perception (in women and men), measured BMI and BMI discordance in women are associated with depression..

Occurrence of metachronous second primary cancer in head and neck cancer survivors: A systematic review and meta-analysis of the literature.

OBJECTIVE: Head and neck cancer (HNC) is the sixth leading cancer worldwide with approximately 600,000 new cases per year. Several studies suggest that HNC survivors may have an increased risk of developing second primary cancers (SPCs). A systematic review and meta-analysis was performed aiming to quantify the overall and site-specific risk of metachronous SPCs in HNC survivors. METHODS: PubMed, Web of Science and Scopus were searched to identify studies published until October 2019. Studies investigating the standardised incidence ratio (SIR) of metachronous SPC were included. A random-effects meta-analysis was performed to calculate the overall and site-specific SIRs. Newcastle-Ottawa Scale was used to assess the study's quality. Heterogeneity was quantified using the I2 statistics and explored using meta-regression. RESULTS: Twenty-six studies were included in the systematic review. Studies differed by the definition of metachronous SPC used. For the meta-analyses, the studies were grouped according to these definitions. In the three groups, the overall risk of metachronous SPC was increased. The highest SPC risk was for oropharynx, oesophagus and lung. CONCLUSIONS: Head and neck cancer survivors are at increased overall risk of metachronous SPCs. The canonical upper aerodigestive sites, HNLE (head and neck, oesophagus and lung), were the SPC sites with the highest risk. IMPLICATION FOR CANCER SURVIVORS: Our results emphasise the importance of targeted surveillance strategies aimed at early detection and tertiary preventive interventions.