The Cross-sectional and Longitudinal Association Between Thyroid Function and Depression: A Population-Based Study.

CONTEXT: An association of thyroid function with mood disorders has been widely suggested, but very few studies have examined this association longitudinally. OBJECTIVE: We assessed the cross-sectional and longitudinal association between thyroid function and depression in a population-based cohort. METHODS: A total of 9471 individuals were included in cross-sectional analyses, of whom 8366 had longitudinal data. At baseline, we assessed thyroid function using serum samples (thyrotropin [TSH], free thyroxine (FT4), and thyroid peroxidase antibodies) and depressive symptoms using the Centre for Epidemiologic Studies Depression (CES-D) scale. Incident depressive events (n = 1366) were continuously followed up with the CES-D and clinical interviews. We analyzed the cross-sectional association of thyroid function and thyroid disease with depressive symptoms using linear and logistic regression, and the longitudinal association with Cox proportional hazard models for depressive events. RESULTS: Lower TSH levels and lower and higher FT4 levels were cross-sectionally associated with more depressive symptoms with a B value of -0.07 per 1 unit increase of natural log-transformed TSH (95% CI -0.11; -0.04). Furthermore, hypothyroidism was cross-sectionally associated with less depressive symptoms and hyperthyroidism with more depressive symptoms. Longitudinally, there was a U-shaped association between FT4 and incident depressive events but only in euthyroid participants. CONCLUSION: We show a cross-sectional association between thyroid (dys)function with depressive symptoms, and a U-shaped association between FT4 and incident depressive events in euthyroid individuals. Our findings suggest an association of thyroid function with the risk of developing depression, albeit small. Reverse causation and additional underlying factors may also contribute to the association.

Thyroid Function and the Risk of Prediabetes and Type 2 Diabetes.

CONTEXT: Thyroid hormones are important regulators of glucose metabolism, and studies investigating the association between thyroid function and type 2 diabetes incidence have shown conflicting results. OBJECTIVE: We aimed to combine the evidence from prospective studies addressing the association between thyroid function and type 2 diabetes risk. METHODS: We systematically searched in Embase, Medline (Ovid), Web of Science, Cochrane, and Google Scholar for prospective studies assessing the association of thyroid function and incident type 2 diabetes. Data extraction was performed using a standardized protocol by 2 independent reviewers. We assessed study quality using the Newcastle-Ottawa Scale and pooled hazard ratios (HRs) and 95% CI using random-effects models. RESULTS: From the 4574 publications identified, 7 met our inclusion criteria and were included in the qualitative synthesis. Six publications were included in the meta-analysis. Studies assessed hypothyroidism (6 studies), hyperthyroidism (5 studies), thyrotropin (TSH) in the reference range (4 studies), and free thyroxine (FT4) in the reference range (3 studies) in relation to incident type 2 diabetes. The pooled HR for the risk of type 2 diabetes was 1.26 (95% CI, 1.05-1.52) for hypothyroidism, 1.16 (95% CI, 0.90-1.49) for hyperthyroidism, 1.06 (95% CI, 0.96-1.17) for TSH in the reference range, and 0.95 (95% CI, 0.91-0.98) for FT4 in the reference range. CONCLUSION: Current evidence suggests an increased type 2 diabetes risk in people with hypothyroidism and lower FT4 levels in the reference range. Further population-based studies are needed to address this association given the limited evidence.

Thyroid Status and Brain Circulation: The Rotterdam Study.

CONTEXT: Whether thyroid dysfunction is related to altered brain circulation in the general population remains unknown. OBJECTIVE: We determined the association of thyroid hormones with different markers of brain circulation within community-dwelling elderly people. METHODS: This was a population-based study of 3 subcohorts of the Rotterdam Study, starting in 1989, 2000, and 2006. A total of 5142 participants (mean age, 63.8 years; 55.4% women), underwent venipuncture to measure serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Between 2005 and 2015, all participants underwent phase-contrast brain magnetic resonance imaging to assess global brain perfusion (mL of blood flow/100 mL of brain/minute). Arteriolar retinal calibers were assessed using digitized images of stereoscopic fundus color transparencies in 3105 participants as markers of microcirculation. We investigated associations of TSH, FT4 with brain circulation measures using (non)linear regression models. RESULTS: FT4 (in pmol/L) levels had an inverse U-shaped association with global brain perfusion, such that high and low levels of FT4 were associated with lower global brain perfusion than middle levels of FT4. The difference in global brain perfusion between high FT4 levels (25 pmol/L) and middle FT4 levels (FT4 = 15 pmol/L; P nonlinearity = .002) was up to -2.44 mL (95% CI -4.31; -0.56). Higher and lower levels of FT4, compared with middle FT4 levels, were associated with arteriolar retinal vessels (mean difference up to -2.46 µm, 95% CI -4.98; 0.05 for lower FT4). CONCLUSION: These results suggest that thyroid dysfunction could lead to brain diseases such as stroke or dementia through suboptimal brain circulation that is potentially modifiable.

Thyroid Function and Physical Activity: A Population-Based Cohort Study.

Background: Thyroid hormones are important metabolic regulators exerting effects in multiple systemic functions including muscular and cardiorespiratory function. Thyroid hormones may influence physical activity levels. However, there are currently no studies evaluating the association between thyroid function and physical activity levels in the general population. Methods: In a population-based cohort study between 2006 and 2013, we assessed the cross-sectional and longitudinal (with a mean follow-up time of 5 years) association of serum thyrotropin (TSH) and free thyroxine (fT4) with physical activity (metabolic equivalent task [MET] hours per week). Information on physical activity was collected using a validated questionnaire (Longitudinal Aging Study Amsterdam, median 22.50 MET hours per week). The association of TSH and fT4 with physical activity was examined using linear regression models in the cross-sectional and longitudinal analyses, adjusted for age, sex, lifestyle factors, and cardiovascular disease. In sensitivity analyses, we examined the association between thyroid function and physical activity including only participants within the reference range of thyroid function. We additionally examined moderate and vigorous physical activity separately as outcomes. Results: We included 2470 participants for the cross-sectional analysis (mean age 57.3 years, 58% women) and 1907 participants for the longitudinal analysis (mean age 56.9 years). There was no association between TSH (mIU/L) or fT4 (ng/dL) and physical activity (ß = 0.65, 95% confidence interval [CI, -1.67 to 2.98] and ß = 2.76, [CI -7.15 to 12.66], respectively) on cross-sectional analysis. Similarly, in the longitudinal analyses, we observed no association of TSH (ß = 1.16, [CI -1.31 to 3.63]) or fT4 (ß = -6.63, [CI -17.06 to 3.80]) with physical activity. Conclusions: We did not observe an association between the endogenous thyroid hormone level and total physical activity. Further studies need to be performed to evaluate whether thyroid hormone replacement therapy is associated with physical activity.

Opciones terapéuticas frente a especies de Candida resistentes a las equinocandinas / Therapeutic options in the management of echinocandin resistant Candida species

Introducción: La infección por levaduras del género Candida representa la causa más común de infecciones fúngicas invasivas. Su alta incidencia y la creciente resistencia frente a los azoles y, recientemente, a las equinocandinas ha generado la necesidad de buscar nuevas alternativas farmacológicas. Esta revisión presenta las principales alternativas farmacológicas en estudio frente a Candida resistente a equinocandinas. Métodos: Se buscó literatura referente al tema en las bases de datos Bireme, Clinical Key, Embase, Cochrane, Lilacs, Pubmed y Scopus. Se incluyeron 15 artículos en esta revisión. Resultados: Se exploran diferentes alternativas, incluyendo el aumento de dosis de las equinocandinas, su combinación con otros medicamentos y nuevos compuestos en estudio. Conclusión: A pesar de que las infecciones por Candida resistente a equinocandinas aún representan un desafío, dos alternativas farmacológicas se presentan como promisorias: la combinación con medicamentos existentes como el diclofenaco y nuevos compuestos que se encuentran actualmente en fase II de estudios clínicos.

Introduction: Candida yeasts infections represent the most common cause of invasive fungal infections. Its high incidence and increasing resistance to azoles and, recently, to echinocandins has generated the need to find new therapeutic options. This review presents the main pharmacological alternatives in research against echinocandins resistant Candida. Methods: A search was conducted in the databases of Bireme, Clinical Key, Embase, Cochrane, Lilacs, Pubmed and Scopus. 15 articles were included in this review. Results: Several alternatives are explored, including increased doses of echinocandins, combination with other drugs and new compounds under study. Conclusion: Although resistant Candida infections still represent a challenge, two pharmacological approaches show promise: The combination with existing medicaments such as diclofenac, and new compounds that are currently in Phase II of clinical trials.