Serum 25-hydroxy vitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes

Objective People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxy vitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. Research design and methods The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction, stroke) and microvascular (retinopathy, nephropathy, neuropathy, and amputation) disease were analysed with Cox proportional-hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial. Results 50% of the patients had low vitamin D concentrations, as indicated by median blood 25OH-D concentration of 49nmol/L. These patients with a blood 25OH-D concentration < 50nmol/L had a higher cumulative incidence of macrovascular and microvascular events than those with levels ≥ 50nmol/L. Multivariate analysis, stratified by treatment and adjusted for relevant confounders, identified blood 25OH-D concentration as an independent predictor of macrovascular events. A 50nmol/L difference in blood 25OH-D concentration was associated with a 23% (P=0.007) change in risk of macrovascular complications during the study and further adjustments for seasonality, hs-CRP and physical activity level had little impact. The unadjusted risk of microvascular complications was 18% (P=0.006) higher during the study, though the excess risk declined to 11-14% and lost significance with adjustment for HbA1C, seasonality or physical activity. Conclusions Low blood 25OH-D concentrations are associated with an increased risk of macrovascular and microvascular disease events in type 2 diabetes. However, a causal link remains to be demonstrated

Metastatic colorectal cancer to a primary thyroid cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment

Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 through 3 (VEGFR1-VEGFR3), fibroblast growth factor receptors 1 through 4 (FGFR1-FGFR4), platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in patients with advanced, radioiodine-refractory, differentiated thyroid cancer (RR-DTC)

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Clinical update in aspects of the management of autoimmune thyroid diseases

Aspects of autoimmune thyroid disease updated in this review include: immunoglobulin G4 (IgG4)-related thyroid disease (Riedel's thyroiditis, fibrosing variant of Hashimoto's thyroiditis, IgG4-related Hashimoto's thyroiditis, and Graves' disease with elevated IgG4 levels); recent epidemiological studies from China and Denmark indicating that excess iodine increases the incidence of Hashimoto's thyroiditis and hypothyroidism; immunomodulatory agents (ipilimumab, pembrolizumab, nivolumab) activate immune response by inhibiting T-cell surface receptors which down-regulate immune response, i.e., cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 pathways; alemtuzumab is a humanised monoclonal antibody to CD52 which causes immune depletion and thyroid autoimmune disease especially Graves' hyperthyroidism; small molecule ligand (SML) agonists which activate receptors, SML neutral antagonists, which inhibit receptor activation by agonists, and SML inverse agonists which inhibit receptor activation by agonists and inhibit constitutive agonist independent signaling have been identified. SML antagonism of thyroid-stimulating hormone-receptor stimulatory antibody could treat Graves' hyperthyroidism and Graves' ophthalmopathy; and thyroxine treatment of subclinical hypothyroidism can produce iatrogenic subclinical hyperthyroidism with the risk of atrial fibrillation and osteoporosis. The increased risk of harm from subclinical hyperthyroidism may be stronger than the potential benefit from treatment of subclinical hypothyroidism

Studies on the aetiology and evaluation of thyroid disease

This thesis is concerned with two broad categories of thyroid related research: the aetiology of autoimmune thyroid disease, and the nuclear basis of thyroid hormone action. Whereas the first is directly related to disease, the research in the second area is intended as a contribution to eventual better understanding of the pathophysiology of thyroid dysfunction, and nonthyroidal illness as it affects thyroid hormone action. The research concerning the aetiology of autoimmune thyroid disease utilized the technique of T lymphocyte migration inhibition testing and was designed to test the hypothesis of suppressor T cell deficiency as a pathogenetic mechanism in autoimmune thyroid disease. Migration of T lymphocytes in the presence or absence of specific antigen was displayed by projection microscopy and measured by planimetry. Inhibition in response to thyroid antigen was found in Graves' disease (GD) and Hashimoto's thyroiditis (HT) but not in normal individuals. The addition of a low ratio of normal T lymphocytes to the GD or HT T lymphocytes abolished the migration inhibition whereas admixture with other GD or HT lymphocytes did not, suggesting the possibility that a specific T lymphocyte deficit, i.e. in suppressor cell function, was being corrected

Insulinoma presenting with post-prandial hypoglycaemia following fundoplication

Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (68Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging

Multi-trauma secondary to hypocalcaemia-induced seizure:A case report

AbstractIntroductionFractures are known sequelae of seizures. We present a young male with bilateral acetabula and surgical neck of humerus (SNOH), right neck of femur (NOF) and thoracolumbar fractures in the context of a hypocalcaemic seizure secondary to severe malnutrition, secondary hyperparathyroidism and vitamin D deficiency. The authors believe that numerous severe injuries in a single patient secondary to seizure are extremely rare and have not been seen in the literature.Case reportA 25-year-old male presented to A&E following a collapse. He described limited movement and pain in all four limbs and collateral history described a generalised tonic–clonic seizure. XR and CT identified pelvic, femoral and humeral fractures, as well as compression fractures of T11, T12 and L1 vertebrae. His pelvic, femoral and SNOH fractures all required ORIF with intra-operative biopsy revealing abnormal bone quality. His spinal fractures did not require management.His young age and severe injuries prompted endocrinology and neurological evaluation. These revealed severe malnutrition secondary to behavioural and dietary factors with severe hypocalcaemia, secondary hyperparathyroidism and vitamin D deficiency. His metabolic and nutritional deficits were replaced intravenously and orally and his seizure attributed to hypocalcaemia.Discussion and conclusionClinical suspicion for fractures should be high as the rate of fracture following seizure is approximately 6% [1]. Close evaluation and tertiary survey should be completed as missed musculoskeletal injury has been reported to be over 10% [2] and pre-existing medical and social risk factors may increase the incidence of these injuries [3–4].Given the young man's presentation, a high clinical suspicion was held for an underlying syndrome such as osteomalacia. Secondary to early aggressive treatment, a biopsy performed was non-diagnostic and features of osteomalacia were not present. Due to the potential consequences of a seizure, the authors recommend individuals who present with seizure or collapse be thoroughly examined and investigated to ensure no co-existing injury or pathology

Effect of loop diuretics and nonsteroidal antiinflammatory drugs on thyrotropin release by rat anterior pituitary cells in vitro

Chen-Fee Lim, Nicole M. Loidl, Jennifer A. Kennedy, Duncan J. Topliss, Jan R. Stockig