Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: Very low carbohydrate ketogenic diet (KD) therapy has been associated with skeletal demineralization in children with drug-resistant epilepsy, but the cause of this association is unclear. Recently, interest in the KD has grown owing to its potential benefits for other illnesses including cancer, type 2 diabetes, obesity, and polycystic kidney disease. Summaries of the best available evidence regarding effects of a KD on skeletal health are lacking.

Recent findings: Recent rodent studies found that a KD can harm the growing skeleton, which corroborates most but not all studies in pediatric patients. Proposed mechanisms include chronic metabolic acidosis and depressed osteoanabolic hormones. Relative to other weight-reducing diets, a weight-reducing KD for treatment of obesity and/or type 2 diabetes in adults has not been associated with adverse skeletal effects. By contrast, recent evidence suggests that adaptation to a eucaloric KD may impair bone remodeling in elite adult athletes. Discrepancies in the literature may relate to differences between study populations and in diet formulation.

Summary: Attention to skeletal health is warranted when using KD therapy given the uncertainty in the literature and suggestive harms in certain populations. Future research should focus on potential mechanisms of injury.

Purpose of review: The relationships between bone vasculature and bone microstructure and strength remain incompletely understood. Addressing this gap will require in vivo imaging capabilities. We describe the relevant vascular anatomy of compact bone, review current magnetic resonance imaging (MRI)-based techniques that allow in vivo assessment of intracortical vasculature, and finally present preliminary studies that apply these techniques to investigate changes in intracortical vessels in aging and disease.

Recent findings: Ultra-short echo time MRI (UTE MRI), dynamic contrast-enhanced MRI (DCE-MRI), and susceptibility-weighted MRI techniques are able to probe intracortical vasculature. Applied to patients with type 2 diabetes, DCE-MRI was able to find significantly larger intracortical vessels compared to nondiabetic controls. Using the same technique, a significantly larger number of smaller vessels was observed in patients with microvascular disease compared to those without. Preliminary data on perfusion MRI showed decreased cortical perfusion with age.

Summary: Development of in vivo techniques for intracortical vessel visualization and characterization will enable the exploration of interactions between the vascular and skeletal systems, and further our understanding of drivers of cortical pore expansion. As we investigate potential pathways of cortical pore expansion, appropriate treatment and prevention strategies will be clarified.

Purpose of review: The incretin hormones, glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), have been shown to decrease bone resorption in humans. The aim of this review is to collate evidence and current advances in the research within the last year on the effect of incretins on skeletal health.

Recent findings: Preclinical studies show potential direct beneficial effects on bone by GLP-1 and GIP, however real world epidemiological data show no effects of GLP-1 receptor analogues on fracture risk. This may be due to the weight loss accompanied by GLP-1 treatment which may have detrimental effects on bone. GIP is shown to reduce bone resorption and increase bone formation. Further evidence suggests an additive effect of GIP and glucagon like peptide-2, which could affect bone by different mechanisms.

Summary: GIP and GLP-1 based therapies are more widespread used and may have potential beneficial effects on bone, possibly counterbalanced by weight loss. Long-term effects and side-effects of GIP or GIP/ GLP-2 co-administration remain to be elucidated, and longer term treatment trials are needed.

Purpose of review: Adrenal insufficiency (AI) is the clinical manifestation of deficient production of glucocorticoids with occasionally deficiency also in mineralocorticoids and adrenal androgens and constitutes a fatal disorder if left untreated. The aim of this review is to summarize the new trends in diagnostic methods used for determining the presence of AI.

Recent findings: Novel aetiologies of AI have emerged; severe acute respiratory syndrome coronavirus 2 infection was linked to increased frequency of primary AI (PAI). A new class of drugs, the immune checkpoint inhibitors (ICIs) widely used for the treatment of several malignancies, has been implicated mostly with secondary AI, but also with PAI. Salivary cortisol is considered a noninvasive and patient-friendly tool and has shown promising results in diagnosing AI, although the normal cut-off values remain an issue of debate depending on the technique used. Liquid chromatography-mass spectrometry (LC-MS/MS) is the most reliable technique although not widely available.

Summary: Our research has shown that little progress has been made regarding our knowledge on AI. Coronavirus disease 2019 and ICIs use constitute new evidence on the pathogenesis of AI. The short synacthen test (SST) remains the 'gold-standard' method for confirmation of AI diagnosis, although salivary cortisol is a promising tool.

Purpose of review: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) represent a heterogenous group of rare tumors emanating from neuroendocrine cells that are clinically silent for prolonged periods of time without detection. Traditional biomarkers lack sufficiently high enough specificity and sensitivity for these tumors and their secreted products. New molecules are sought to improve accuracy of detection and monitoring of GEP-NENs. The purpose of this review is to highlight recent advances in the discovery of novel biomarkers and their potential characteristics and utility as markers of GEP-NENs.

Recent findings: Several recent GEP-NEN investigations regarding NETest demonstrate superior sensitivity and specificity in diagnosis and disease monitoring as compared with chromogranin A. Among several tissue-based emergent candidate molecules as biomarkers for GEP-NEN INSM1 has demonstrated consistently excellent characteristics when compared with traditional markers including chromogranin A, synaptophysin, and CD56.

Summary: For the diagnosis and clinical monitoring of NEN, there still exists a considerable need for better biomarkers. Novel technology has resulted in a promising liquid biopsy for the detection and monitoring of GEP-NENs. The search for improved tissue biomarkers has resulted in identification of one potential candidate whereas several others remain in the investigatory phase.

Purpose of review: The adrenal glands produce some of the most essential for life hormones, including cortisol and other steroids, and catecholamines. The former is produced from the adrenal cortex, whereas the latter is from the medulla. The two parts are anatomically and functionally distinct and it would be impossible in the context of one short article to cover all molecular updates on both the cortex and the medulla. Thus, in this review, we focus on the molecular tools available for diagnosing adrenocortical diseases, such as adrenal insufficiency, Cushing and Conn syndromes, and their potential for advancing medical care and clinical outcome.

Recent findings: The advent of next generation sequencing opened doors for finding genetic diseases and signaling pathways involved in adrenocortical diseases. In addition, the combination of molecular data and clinicopathologic assessment might be the best approach for an early and precise diagnosis contributing to therapeutic decisions and improvement of patient outcomes.

Summary: Diagnosing adrenocortical diseases can be challenging; however, the progress of molecular tools for adrenocortical disease diagnosis has greatly contributed to early detection and to meliorate patient outcomes.

Purpose of review: Glucocorticoid withdrawal syndrome (GWS) can develop after withdrawing exposure to supraphysiological levels of endogenous or exogenous glucocorticoids due to an established physical dependence. It is characterised by symptoms similar to adrenal insufficiency but needs to be regarded as a separate entity. GWS is often under-recognised in clinical practice and affected patients can experience significant impairment in their quality of life.

Recent findings: A cornerstone in GWS management is adequate patient education and reassurance that symptoms are expected and typically temporary. Patients with endogenous Cushing's syndrome need to be aware that psychopathology may persist into the postoperative period. GWS is more likely to develop in severe Cushing's syndrome and in patients with very low levels of cortisol after surgery. Postoperatively, glucocorticoid replacement should be initiated and tapered in an individualised approach but there is currently no consensus on the best tapering strategy. If symptoms of GWS develop, glucocorticoid replacement ought to be temporarily increased to the previous, well tolerated dose. No randomised studies have thus far compared regimens for withdrawing glucocorticoids after treatment for anti-inflammatory or immunosuppressive causes to determine the best and safest tapering strategy. One open-label, single-arm trial in patients with asthma has recently proposed a personalised glucocorticoid tapering regimen which included the systematic assessment of adrenal function.

Summary: Awareness of GWS by treating physicians and patient education are essential. Evidence on optimal GWS management after Cushing's syndrome treatment is scarce, but new data are emerging for tapering after long-term glucocorticoid treatment.

Purpose of review: Review the literature on the surgical management of adrenal diseases, highlighting the various surgical approaches and their respective pros and cons.

Recent findings: Minimally invasive adrenalectomy is commonly used for small and benign adrenal tumors, whereas open adrenalectomy is preferred for larger tumors and primary adrenal malignancy. Although minimally invasive adrenalectomy results in shorter recovery and fewer complications compared with open, the latter offers better oncologic outcomes in the setting of primary adrenal malignancy. Adrenalectomy is performed transabdominally or retroperitoneoscopically, both yielding equivalent results and recovery. Traditional laparoscopic or robotic equipment can be utilized for either minimally invasive approach. Subtotal adrenalectomy may be appropriate for patients with genetically associated pheochromocytoma to preserve cortical function and reduce the risk of adrenal insufficiency. However, the potential benefits of sparing adrenal function must be weighed against the risk of recurrence.

Summary: Adrenalectomy is becoming increasingly common worldwide. For benign and small adrenal tumors, minimally invasive adrenalectomy is generally considered the standard approach, while open adrenalectomy is preferred for primary adrenal malignancy and larger tumors. Subtotal adrenalectomy may be appropriate for patients with bilateral adrenal pheochromocytoma, as it can reduce the need for lifelong glucocorticoid dependency.