Endocrine reviews最新文献

Uterine fibroids (UFs) are highly prevalent benign tumors, primarily affecting women of reproductive age. The prevalence of UFs is estimated at 25% to 70% to 80%, with significantly higher rates among African women. Recent investigations have unveiled a link between vitamin D (VD) levels and the presence of UFs. Current data show that individuals with sufficient VD levels are at a reduced risk of developing UFs. This review aims to synthesize the latest discoveries on the involvement of VD in the pathophysiology of UFs, as well as to explore its feasible therapeutic applications. The mechanisms underlying the potential of VD to diminish the risk of UF development and to inhibit their growth are multifaceted and include its antiproliferative effects, the induction of apoptosis, suppression of angiogenesis, or the modulation of enzyme activity. The potential of VD and its analogues as promising agents for managing and preventing UFs was demonstrated. However, further research is needed to clarify the biological mechanisms behind the role of VD in UF pathophysiology, and its definitive efficacy has to be confirmed through randomized clinical trials.

The thyroid is exposed to DNA damage induced by normal physiological processes (eg, oxidative stress resulting from thyroid hormone synthesis or mitochondrial respiration) or through environmental insults (eg, environmental pollutants, ionizing radiation exposure). Robust antioxidative stress defense and DNA repair mechanisms protect thyrocyte genome integrity, but defective or dysregulated DNA repair pathways have been implicated in thyroid pathology, including autoimmune thyroid disease and thyroid malignancy. In thyroid cancer, disturbed antioxidative stress defense, Mismatch Repair, Non-Homologous End-Joining, or DNA damage response pathways contribute to both the onset and progression of the disease. The insight into mechanisms governing thyrocyte genome integrity may help to gain better understanding of the pathology and suggest novel therapeutic regimens, urgently needed in treatment-refractory disease. In the current review, we provide comprehensive description of the exogenous and endogenous factors, as well as DNA repair mechanisms influencing thyrocyte genome integrity. Moreover, we pinpoint major research avenues that should be pursued in future research. This information will be valuable in directing new discoveries to better understand thyroid disease pathomechanisms, as well as aid development of novel diagnostic and therapeutic tools.

One of the major metabolic functions of glucocorticoids (GC) is to maintain circulating glucose levels during stress, as glucose is the preferred energy source for the brain. Because of their potent anti-inflammatory and immune modulatory activities, GC are frequently used to treat inflammatory and autoimmune diseases. Chronic GC exposure, which can be a result of long-term GC pharmacotherapy and prolonged stress, however, causes undesired adverse effects that include hyperglycemia and insulin resistance. These adverse effects limit the application of GC therapy. GC act through an intracellular GC receptor (GR), a transcriptional regulator, to modulate the transcriptional rate of specific genes to exert physiological responses. The liver is a major target tissue of GC to modulate glucose homeostasis. In this review, we discuss the mechanisms of GR-activated transcription of genes involved in glucose metabolism and how hepatic GR primary target genes participate in the regulation of insulin sensitivity and glucose homeostasis. Transcriptional coregulators involved in GR-regulated transcription of glucose metabolism genes and signaling pathways specifically activated upon chronic GC exposure to induce glucose disorders are introduced. Metabolic profiles of liver-specific GR knockout mice are also reviewed. Finally, individual-specific GC responses and mechanisms underlying these phenomena are discussed. Overall, more extensive studies of the mechanisms of GR-regulated hepatic glucose homeostasis not only will expand our knowledge of the regulation of metabolic homeostasis but are also critical for developing improved GC pharmacotherapy and novel approaches to tackle metabolic disorders by targeting GR.

Adipose tissue has emerged as a central regulator of human physiology, with its dysfunction driving the global rise in obesity-associated diseases, such as type 2 diabetes, cardiovascular and liver diseases, and several cancers. Once thought to be inert, adipocytes are now recognized as dynamic, responsive cells essential for energy homeostasis and interorgan communication, including the brain. Distinct adipose depots support specialized functions across development, sex, and aging. Technologies like single-cell RNA sequencing are unraveling depot-specific mechanisms, with the potential of identifying new therapeutic targets. This review highlights major scientific advancements leading to our current appreciation of the pivotal role of adipose tissue in health and disease. Many key discoveries in this field have been catalyzed by National Institutes of Health funding, particularly through the National Institute of Diabetes, Digestive and Kidney Diseases, now celebrating its 75th anniversary.

Adults with adrenal cortisol insufficiency (ACI) often report cognitive dysfunction, especially in memory processing and executive function. Only a few studies have objectively compared cognitive function as the primary outcome between patients with ACI and controls, and these efforts have yielded inconsistent results. In this review, we examine the challenges facing researchers studying cognitive function in adult patients with ACI. We consider the effect of dysregulated cortisol on cognition in patients with ACI, and the inability of current guideline-recommended glucocorticoid (GC) treatment regimens to accurately reproduce circadian and ultradian cortisol secretion rhythms. Factors that contribute to inter- and intra-individual response to GC are presented; the indirect effects of ACI comorbidities, complications, and symptoms on cognitive dysfunction are reviewed; and obstacles to employing neurocognitive testing are identified. Finally, we outline potential approaches to studying cognition in ACI using well-designed studies that account for the complexities and gaps in ACI research.

This narrative review written by experts aims to provide a comprehensive synthesis of current knowledge and guidelines on lung carcinoids, emphasizing the multidimensional approach required for effective diagnosis and management. The manuscript will: i) Define and classify lung carcinoids in accordance with the latest WHO classification system, and emphasize the importance of molecular markers for precise subtyping; ii) Analyze epidemiological trends, discuss prevalence, incidence, and mortality rates, alongside key risk factors including genetic predispositions (MEN1) and precursor lesions such as diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH); iii) Investigate the etiology and carcinogenesis of lung carcinoids, including insights into the molecular hallmarks and pathways that underlie tumor development and progression; iv) Detail clinical presentations, distinguishing pulmonary symptoms from secretory syndromes (carcinoid syndrome and Cushing's syndrome), supported by visual aids to elucidate symptom prevalence and implications; v) Present an integrated diagnostic approach, encompassing state-of-the-art imaging modalities (CT, MRI, 68Ga-SSA-PET-CT) and advanced molecular pathology techniques; vi) Outline evidence-based treatment strategies, addressing early-stage interventions, systemic therapies, locoregional therapies, and emerging modalities such as immunotherapy and agnostic approaches; vii) Explore the role of multidisciplinary management, highlighting the critical importance of tumor boards dedicated to lung carcinoids and provide a checklist of key items for comprehensive case discussion and decision-making; viii) Conclude with future perspectives, identifying gaps in current knowledge and suggest directions for research to enhance diagnosis, treatment, and overall patient quality of life.