Nicotine increases hepatocyte transthyretin turnover: A possible mechanism for the protective effect of smoking on preeclampsia?

Transthyretin is a thyroid hormone binding protein with a major role in the distribution of thyroid hormones to peripheral tissues. In preeclampsia, the failing placenta releases soluble endoglin into the maternal circulation causing systemic vascular dysfunction. Our group has previously shown that transthyretin binds to soluble endoglin and is taken up as a complex into hepatocytes.

A Case of Enfortumab Vedotin-Associated Diabetic Ketoacidosis With Severe Insulin Resistance in a Nondiabetic Woman.

Enfortumab vedotin is a novel antibody-drug conjugate (ADC) approved to treat urothelial carcinoma. One rarely reported adverse effect has been life-threatening diabetic ketoacidosis (DKA) driven by profound insulin resistance. We report a case of a 62-year-old nondiabetic woman with metastatic urothelial carcinoma who experienced DKA following her third dose of enfortumab vedotin, with extreme insulin requirements of > 1000 units daily, and full resolution of insulin requirement by day 7 of admission.

Subclinical Hyperthyroidism and Cardiovascular Disease.

In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality.

The effect of three years of vitamin D supplementation on erectile dysfunction: Results from the randomized placebo-controlled D-Health Trial.

Background & Aims: Erectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial.

The Effect of Vitamin D Supplementation on Hypothyroidism in the Randomized Controlled D-Health Trial.

Hypothyroidism is common, and in iodine-sufficient areas, it is primarily caused by autoimmune destruction of the thyroid gland. Observational studies have consistently shown an inverse association between serum 25-hydroxyvitamin D concentration and autoimmune diseases; however, there is a lack of evidence from randomized controlled trials to support a benefit of vitamin D supplementation, particularly for autoimmune thyroid diseases. We, therefore, aimed to assess the effect of vitamin D supplementation on the incidence of hypothyroidism.

Obesity and thyroid cancer risk.

Purpose Of Review: This review explores recent evidence assessing the relationship between obesity and thyroid cancer.

Recent Findings: Consistent evidence from observational studies suggests that obesity increases the risk of thyroid cancer. The relationship persists when alternative measures of adiposity are used, but the strength of association may vary according to the timing and duration of obesity and how obesity or other metabolic parameters are defined as exposures.

Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial.

Objective: To investigate whether supplementing older adults with monthly doses of vitamin D alters the incidence of major cardiovascular events.

Design: Randomised, double blind, placebo controlled trial of monthly vitamin D (the D-Health Trial). Computer generated permuted block randomisation was used to allocate treatments.

The effect of vitamin D supplementation on the gut microbiome in older Australians - Results from analyses of the D-Health Trial.

Observational studies suggest a link between vitamin D and the composition of the gut microbiome, but there is little evidence from randomized controlled trials of vitamin D supplementation. We analyzed data from the D-Health Trial, a randomized, double-blind, placebo-controlled trial. We recruited 21,315 Australians aged 60-84 y and randomized them to 60,000 IU of vitamin D or placebo monthly for 5 y.

Thyroid cancer.

The past 5-10 years have brought in a new era in the care of patients with thyroid cancer, with the introduction of transformative diagnostic and management options. Several international ultrasound-based thyroid nodule risk stratification systems have been developed with the goal of reducing unnecessary biopsies. Less invasive alternatives to surgery for low-risk thyroid cancer, such as active surveillance and minimally invasive interventions, are being explored.

The effect of monthly vitamin D supplementation on fractures: a tertiary outcome from the population-based, double-blind, randomised, placebo-controlled D-Health trial.

Background: Low serum 25-hydroxy vitamin D concentration is associated with increased fracture risk. It is uncertain whether vitamin D supplementation reduces fractures, or whether intermittent doses are harmful. We aimed to investigate if supplementing adults living in Australia with monthly doses of 60 000 international units (IU) vitamin D for 5 years or less altered the rate of fractures.

Vitamin D and Sun Exposure: A Community Survey in Australia.

Sun exposure carries both harms and benefits. Exposing the skin to the sun is the main modifiable cause of skin cancers, which exert a considerable health and economic burden in Australia. The most well-established benefit of exposure to ultraviolet (UV) radiation is vitamin D production.

Vitamin D supplementation and hospitalization for infection in older adults: A post-hoc analysis of data from the Australian D-Health Trial.

Background: Evidence suggests that vitamin D influences the immune system. Recent studies indicate that vitamin D supplementation may reduce the severity of infections, but this has not been confirmed.

Objectives: The objective of this study was to assess the effect of vitamin D supplementation on hospitalization for infection.

Vitamin D supplementation and cognition-Results from analyses of the D-Health trial.

Background: Observational studies have consistently found a link between low serum 25-hydroxyvitamin D concentration and higher risk of cognitive impairment. Results from randomized controlled trials have been mixed, and few have been conducted in the general population.

Methods: We recruited 21,315 community-dwelling Australians aged between 60 and 84 years to participate in the D-Health Trial, a randomized, double-blind, placebo-controlled trial.

Transthyretin binds soluble endoglin and increases its uptake by hepatocytes: A possible role for transthyretin in preeclampsia?

Background: Preeclampsia is a common but life-threatening condition of pregnancy. It is caused by poor placentation resulting in release of trophoblast material (including soluble endoglin (sEng)) into the maternal circulation leading to maternal vascular dysfunction and to the life-threatening condition of eclampsia. The only cure is early delivery, which can have lifelong consequences for the premature child.

Effect of vitamin D supplementation on depression in older Australian adults.

Objectives: To investigate whether vitamin D supplementation reduces depressive symptoms and incidence of antidepressant use.

Methods: We used data from the D-Health Trial (N = 21,315), a randomized double-blind placebo-controlled trial of monthly vitamin D for the prevention of all-cause mortality. Participants were Australians aged 60-84 years.

The effect of vitamin D supplementation on pain: an analysis of data from the D-Health randomised controlled trial.

Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial).

Vitamin D Supplementation and the Incidence of Cataract Surgery in Older Australian Adults.

Purpose: Observational studies suggest that higher serum 25-hydroxy vitamin D (25(OH)D) concentration may be associated with lower risk of cataract. However, no randomized controlled trials have assessed the effect of vitamin D supplementation on the incidence of cataract. We aimed to assess whether vitamin D supplementation reduces the incidence of cataract surgery.

The effect of vitamin D supplementation on risk of keratinocyte cancer: an exploratory analysis of the D-Health randomized controlled trial.

Background: Vitamin D may play a role in prevention of keratinocyte cancer (KC), but observational studies examining the association between serum 25-hydroxy vitamin D concentration and KC are largely uninformative because sun exposure causes both KC and vitamin D production. There is scant evidence from clinical trials of supplementary vitamin D.

Objectives: To examine the effect of vitamin D supplementation on the risk of developing KC.

Vitamin D Supplementation and Antibiotic Use in Older Australian Adults: An Analysis of Data From the D-Health Trial.

Background: Vitamin D supplementation may reduce the risk or severity of infection, but this has been investigated in few large population-based trials. We analyzed data from the D-Health Trial, using prescription of antibiotics as a surrogate for infection.

Methods: The D-Health Trial is a randomized, double-blind, placebo-controlled trial in which 21 315 Australians aged 60-84 years were randomized to 60 000 IU of supplementary vitamin D3 or placebo monthly for 5 years.

Thyroid Dysfunction from Treatments for Solid Organ Cancers.

In recent years, cancer care has been transformed by immune-based and targeted treatments. Although these treatments are effective against various solid organ malignancies, multiple adverse effects can occur, including thyroid dysfunction. In this review, the authors consider treatments for solid organ cancers that affect the thyroid, focusing on immune checkpoint inhibitors, kinase inhibitors, and radioactive iodine-conjugated treatments (I-131-metaiodobenzylguanidine).

Pre-existing Thyroid Autoimmunity and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study of US Active-Duty Personnel.

Purpose: Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies.

Methods: We conducted a case-control study nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date.

Nicotine binds to the transthyretin-thyroxine complex and reduces its uptake by placental trophoblasts.

Background: A supply of maternal thyroid hormone (thyroxine, T4) is essential for normal human fetal development. Human placental trophoblasts synthesize, secrete and take up the T4 binding protein transthyretin, providing a route for maternal T4 to enter the placenta. Transthyretin is also involved in T4 transport in other tissues such as the brain choroid plexus.

The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality.

Background: The effect of supplementing unscreened adults with vitamin D on mortality is unclear. We aimed to determine whether monthly doses of vitamin D influenced mortality in older Australians.

Methods: We did a randomised, double-blind, placebo-controlled trial of oral vitamin D supplementation (60 000 IU per month) in Australians 60 years or older who were recruited across the country via the Commonwealth electoral roll.