Journal: Endocrine connections
Background: The water deprivation test is the gold standard test to differentiate central or nephrogenic diabetes insipidus (DI) from primary polydipsia (PP) in patients with polyuria and polydipsia. Few studies have addressed the diagnostic performance of this test. Methods: The aim of this retrospective cohort study was to evaluate the diagnostic performance of the standard water deprivation test, including plasma arginine vasopressin (AVP) measurements, in 40 consecutive patients with polyuria. We compared initial test results to the final clinical diagnosis, i.e., no DI, central DI or nephrogenic DI. Median length of follow up was 8 years. In a subset of 10 patients, the novel marker copeptin (CP) was measured in plasma. Results: Using the final diagnosis as gold standard, a threshold for urine osmolality of > 800 mOsmol/kg after water deprivation yielded a sensitivity and specificity of 96% and 100% for diagnosing PP. Sensitivity increased to 100% if the cut off value for urine osmolalilty was set at 680 mOsmol/kg. Plasma AVP levels did not differ between patient groups and did not differentiate between central DI, nephrogenic DI or PP. In all three patients with central DI, plasma CP was <2.5 pmol/L with plasma osmolality > 290 mOsmol/kg, and >2.5 pmol/L in patients without DI. Conclusions: The optimal cut-off value for differentiating PP from DI during a water deprivation test was urine osmolality > 680 mOsmol/kg. Differentiating between central and nephrogenic DI should be based on clinical judgement since AVP levels did not discriminate.
The growth hormone (GH)-insulin-like growth factor (IGF)-I axis is a key endocrine mechanism regulating linear growth in children. While paediatricians have a good knowledge of GH secretion and assessment, understanding and use of measurements of the components of the IGF system are less current in clinical practice. The physiological function of this axis is to increase the anabolic cellular processes of protein synthesis and mitosis, and reduction of apoptosis, with each being regulated in the appropriate target tissue. Measurement of serum IGF-I and IGFBP-3 concentrations can complement assessment of GH status in the investigation of short stature and contribute to prediction of growth response during GH therapy. IGF-I monitoring during GH therapy also informs the clinician about adherence and provides a safety reference to avoid over-dosing during long-term management.
Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. Besides hyperandrogenism, oligomenorrhea and fertility issues, it is associated with a high prevalence of metabolic disorders and cardiovascular risk factors. Several genetic polymorphisms have been identified for possible associations with cardiometabolic derangements in PCOS. Different PCOS phenotypes differ significantly in their cardiometabolic risk which is worsening with severity of androgen excess. Due to methodological difficulties longer time-scale data about cardiovascular morbidity and mortality in PCOS and about possible beneficial effects of different treatment interventions is missing leaving many issues regarding cardiovascular risk unresolved.
Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increase blood flow and triglyceride clearance in subcutaneous abdominal adipose tissue in lean humans. The present experiments were performed to determine whether the increase involves capillary recruitment. Eight lean healthy volunteers were studied before and after 1-h infusion of GIP or saline during a hyperglycemic-hyperinsulinemic clamp, raising plasma glucose and insulin to postprandial levels. Subcutaneous abdominal adipose tissue blood flow (ATBF) was measured by the 133Xenon clearance technique, and microvascular blood volume was determined by contrast-enhanced ultrasound imaging. During infusion of saline and the clamp, both ATBF (2.7 ± 0.5 ml/min, 100 g/tissue) and microvascular blood volume remained unchanged throughout the experiments. During GIP infusion and the clamp, ATBF increased ~fourfold to 11.4 ± 1.9 ml/min 100 g/tissue, P<0.001. Likewise, the contrast-enhanced ultrasound signal intensity, a measure of the microvascular blood volume, increased significantly one hour after infusion of GIP and the clamp (P=0.003), but not in the control experiments. In conclusion, the increase in ATBF during GIP infusion involves recruitment of capillaries in healthy lean subjects, which probably increases the interaction of circulating lipoproteins with lipoprotein lipase, thus promoting adipose tissue lipid uptake.
Concern has been raised over chemical induced disruption of ovarigenesis during fetal life resulting in long-lasting consequences only manifesting themselves much later during adulthood. A growing body of evidence suggest that prenatal exposure to the mild analgesic acetaminophen/paracetamol can cause such a scenario. In this Review, we therefore discuss three recent reports that collectively indicating that prenatal exposure in a window around 13.5 days post coitum in both rats and mouse can result in reduced female reproductive health. The combined data show that the exposure results in reduction in primordial follicles, irregular cycling, premature absence of corpus luteum, as well as reduced fertility, resembling premature ovarian insufﬁciency syndrome in humans that is linked to premature menopause. This could be problematic in the Western world where the age at childbirth is continuously being delayed and because acetaminophen is recommended during pregnancy for pain, fever. We therefore highlight an urgent need for more studies to verify these data including both experimental and epidemiological approaches.
This review covers recent findings on the main categories of thyroid hormone disrupting chemicals and their effects on brain development. We draw mostly on epidemiological and experimental data published in the last decade. For each chemical class considered, we deal with not only the thyroid hormone disrupting effects but also briefly mention the main mechanisms by which the same chemicals could modify estrogen and/or androgen signalling, thereby exacerbating adverse effects on endocrine-dependent developmental programs. Further, we emphasize recent data showing how maternal thyroid hormone signalling during early pregnancy affects not only offspring IQ, but also neurodevelopmental disease risk. These recent findings add to established knowledge on the crucial importance of iodine and thyroid hormone for optimal brain development. We propose that prenatal exposure to mixtures of thyroid hormone-disrupting chemicals provides a plausible biological mechanism contributing to current increases in incidence of neurodevelopmental disease and IQ loss.
Neuroinflammatory responses are implicated in depression. The aim was to explore whether depression in patients with type 1 diabetes (T1D) was associated with high circulating galectin-3, controlling for metabolic variables, s-creatinine, life style factors, medication, and cardiovascular complications.
Chromogranin A (CgA) is the major soluble protein co-stored and co-released with catecholamines and can function as prohromone giving rise to several bioactive peptides. This review focuses on these molecules summarizing their physiological functions, their pathogenetic implications and their recent use as biomarkers in several pathological conditions. A thorough literature search of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized key-words such Chromogranin A, Vasostatin-1 and 2, Chromofungin, Chromacin, Pancreastatin, Catestatin, WE-14, Chromostatin, GE-25, Parastatin and Serpinin, and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular and the immune systems and by affecting the glucose or calcium homeostasis. Since some peptides exert similar effects, but other elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenetic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumours, but also in cardiovascular, inflammatory and neuropsychiatric diseases.
Type 2 diabetes (T2D) is a serious disease. The gut microbiota has recently been identified as a new potential risk factor in addition to well-known diabetes risk factors. To investigate the gut microbiota composition in association with the dietary patterns in patients with different glucose tolerance we analyzed 92 patients: with normal glucose tolerance (n=48), prediabetes (preD, n=24), T2D (n=20). Metagenomic analysis was performed using 16SrRNA sequencing. The diet has been studied by a frequency method with a quantitative evaluation of food intake using a computer program. Microbiota in the samples was predominantly represented by Firmicutes, in a less degree by Bacteroidetes. Blautia was a dominanting genus in all samples. The representation of Blautia, Serratia was lower in preD than in T2D patients, and even lower in those with normal glucose tolerance. After the clustering of the samples into groups according to the percentage of protein, fat, carbohydrates in the diet, the representation of the Bacteroides turned to be lower and Prevotella abundance turned to be higher in carbohydrate cluster. There were more patients with insulin resistance, T2D in the fat-protein cluster. Using the Calinski-Harabasz index identified the samples with more similar diets. It was discovered that half of the patients with a high-fat diet had normal tolerance, the others had T2D. The regression analysis showed that these T2D patients also had a higher representation of Blautia. Our study provides the further evidence concerning the structural modulation of the gut microbiota in the T2DM pathogenesis depending on the dietary patterns.
Cranial diabetes insipidus (CDI) is a treatable chronic condition that can potentially develop into a life-threatening medical emergency. CDI is due to the relative or absolute lack of the posterior pituitary hormone vasopressin (AVP), also known as anti-diuretic hormone. AVP deficiency results in uncontrolled diuresis. Complete deficiency can lead to polyuria exceeding 10 L/24 h. Given a functioning thirst mechanism and free access to water, patients with CDI can normally maintain adequate fluid balance through increased drinking. Desmopressin (DDAVP, a synthetic AVP analogue) reduces uncontrolled water excretion in CDI and is commonly used in treatment. Critically, loss of thirst perception (through primary pathology or reduced consciousness) or limited access to water (through non-availability, disability or inter-current illness) in a patient with CDI can lead to life-threatening dehydration. This position can be further exacerbated through the omission of DDAVP. Recent data have highlighted serious adverse events (including deaths) in patients with CDI. These adverse outcomes and deaths have occurred through a combination of lack of knowledge and treatment failures by health professionals. Here, with our guideline, we recommend treatment pathways for patients with known CDI admitted to hospital. Following these guidelines is essential for the safe management of patients with CDI.