Marc Gregory Yu, Daniel Gordin, Jialin Fu, Kyoungmin Park, Qian Li, George Liang King
Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways, which are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of micro- and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid (both vascular and parenchymal) tissue origin, since the profile of diabetes complications ranges from those involving only vascular tissues to those involving mostly parenchymal organs...
August 28, 2023: Endocrine Reviews
Marisel Rosell-Díaz, José Manuel Fernández-Real
The decline in cognitive function and the prevalence of neurodegenerative disorders are among the most serious threats to health in old age. The prevalence of dementia has reached 50 million people worldwide and has become one of the major public health problems. The causes of age-related cognitive impairment are multiple, complex, and difficult to determine. However, type 2 diabetes (T2D) is linked to an enhanced risk of cognitive impairment and dementia. Human studies have shown that patients with T2D exhibit dysbiosis of the gut microbiota...
August 21, 2023: Endocrine Reviews
Pei Chia Eng, Maria Phylactou, Ambreen Qayum, Casper Woods, Hayoung Lee, Sara Aziz, Benedict Moore, Alexander D Miras, Alexander N Comninos, Tricia Tan, Steve Franks, Waljit S Dhillo, Ali Abbara
Obesity-related hypogonadotropic hypogonadism is a well-characterized condition in men (termed male obesity-related secondary hypogonadism; MOSH), however, an equivalent condition has not been as clearly described in women. The prevalence of polycystic ovary syndrome (PCOS) is known to increase with obesity, but PCOS is more typically characterized by increased gonadotropin releasing hormone (GnRH) (and by proxy luteinizing hormone; LH) pulsatility, rather than by the reduced gonadotropin levels observed in MOSH...
August 10, 2023: Endocrine Reviews
Nathan Mullen, James Curneen, Padraig T Donlon, Punit Prakash, Irina Bancos, Mark Gurnell, Michael C Dennedy
Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared to blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for non-surgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine learning algorithms have shown promise in the prediction of PA subtypes, while the development of non-invasive alternatives to adrenal vein sampling (including molecular PET imaging) has made accurate localisation of functioning adrenal nodules possible...
August 9, 2023: Endocrine Reviews
Claudia E Ramirez Bustamante, Neeti Agarwal, Aaron R Cox, Sean M Hartig, Jordan E Lake, Ashok Balasubramanyam
Over the past four decades, the clinical care of people living with HIV (PLWH) evolved from treatment of acute opportunistic infections to the management of chronic, non-communicable comorbidities. Concurrently, our understanding of adipose tissue function matured to acknowledge its important endocrine contributions to energy balance. PLWH experience changes in the mass and composition of adipose tissue depots before and after initiating antiretroviral therapy (ART), including regional loss (lipoatrophy), gain (lipohypertrophy), or mixed lipodystrophy...
August 9, 2023: Endocrine Reviews
Bijal Patel, Kanyada Koysombat, Edouard G Mills, Jovanna Tsoutsouki, Alexander N Comninos, Ali Abbara, Waljit S Dhillo
Kisspeptin (KP) and neurokinin B (NKB) are neuropeptides that govern the reproductive endocrine axis through regulating hypothalamic gonadotropin-releasing hormone (GnRH) neuronal activity and pulsatile GnRH secretion. Their critical role in reproductive health was first identified after inactivating variants in genes encoding for KP or NKB signaling were shown to result in congenital hypogonadotropic hypogonadism (CHH) and a failure of pubertal development. Over the past two decades since their discovery, a wealth of evidence from both basic and translational research has laid the foundation for potential therapeutic applications...
July 20, 2023: Endocrine Reviews
Yuhu Zhao, Xiaole Peng, Qing Wang, Zhiyu Zhang, Liangliang Wang, Yaozeng Xu, Huilin Yang, Jiaxiang Bai, Dechun Geng
The homeostasis of bone microenvironment is the foundation of bone health and comprises two concerted events: bone formation by osteoblasts and bone resorption by osteoclasts. In the early 21st century, leptin, an adipocytes-derived hormone was found to affect bone homeostasis through hypothalamic relay and sympathetic nervous system, involving neurotransmitters like serotonin and norepinephrine. This discovery has provided a new perspective regarding the synergistic effects of endocrine and nervous systems on skeletal homeostasis...
July 17, 2023: Endocrine Reviews
Vladimir Saenko, Norisato Mitsutake
Radiation is an environmental factor that elevates the risk of developing thyroid cancer. Actual and possible scenarios of exposures to external and internal radiation are multiple and diverse. This article reviews radiation doses to the thyroid and corresponding cancer risks due to planned, existing, and emergency exposure situations, and medical, public, and occupational categories of exposures. Any exposure scenario may deliver a range of doses to the thyroid, and the risk for cancer is addressed along with modifying factors...
July 14, 2023: Endocrine Reviews
Gregory L Hundemer, Alexander A Leung, Gregory A Kline, Jenifer M Brown, Adina F Turcu, Anand Vaidya
Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin; biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology...
July 13, 2023: Endocrine Reviews
Lies Langouche, Arno Téblick, Jan Gunst, Greet Van den Berghe
Based on insights obtained during the last decade, the classical concept of an activated hypothalamus-pituitary-adrenocortical (HPA) axis in response to critical illness is in need of revision. After a brief central HPA axis activation, the vital maintenance of increased systemic cortisol availability and action in response to critical illness is predominantly driven by peripheral adaptations rather than by an ongoing centrally-activated several-fold increased production and secretion of cortisol. Besides the known reduction of cortisol binding proteins that increases free cortisol, these peripheral responses comprise suppressed cortisol metabolism in liver and kidney, prolonging cortisol half-life, and local alterations in expression of 11βHSD1, GRα and FKBP51 that appear to titrate increased GRα-action in vital organs and tissues while reducing GRα-action in neutrophils possibly preventing immune-suppressive off-target effects of increased systemic cortisol availability...
July 6, 2023: Endocrine Reviews
Ryan M Marquardt, Dinh Nam Tran, Bruce A Lessey, Md Saidur Rahman, Jae-Wook Jeong
Endometriosis is a prevalent gynecological condition associated with pelvic pain and infertility. Despite more than a century of research, the etiology of endometriosis still eludes scientific consensus. This lack of clarity has resulted in suboptimal prevention, diagnosis, and treatment options. Evidence of genetic contributors to endometriosis is interesting but limited; however, significant progress has been made in recent years in identifying epigenetic role in the pathogenesis of endometriosis through clinical studies, in vitro cell culture experiments, and in vivo animal models...
July 6, 2023: Endocrine Reviews
Shalender Bhasin, Douglas Seals, Marie Migaud, Nicolas Musi, Joseph A Baur
Recent research has unveiled an expansive role of NAD+ in cellular energy generation, redox reactions, and as a substrate or co-substrate in signaling pathways that regulate health-span and aging. This review provides a critical appraisal of the clinical pharmacology and the pre-clinical and clinical evidence for therapeutic effects of NAD+ precursors for age-related conditions, with a particular focus on cardiometabolic disorders, and discusses gaps in current knowledge. NAD+ levels decrease throughout life; age-related decline in NAD+ bioavailability has been postulated to be a contributor to many age-related diseases...
June 26, 2023: Endocrine Reviews
Alexia Carré, Federica Vecchio, Malin Flodström-Tullberg, Sylvaine You, Roberto Mallone
The evidence for an association between coxsackievirus B (CVB) infection, pancreatic islet autoimmunity, and clinical type 1 diabetes is increasing. Results from prospective cohorts and pancreas histopathology studies have provided a compelling case. However, the demonstration of a causal relationship is missing, and is likely to remain elusive until tested in humans by avoiding exposure to this candidate viral trigger. To this end, CVB vaccines have been developed and are entering clinical trials. However, the progress made in understanding the biology of the virus and in providing tools to address the long-standing question of causality contrasts with the scarcity of information about the antiviral immune responses triggered by infection...
July 11, 2023: Endocrine Reviews
Rocio Garcia-Carbonero, Beatriz Anton-Pascual, Andrea Modrego, Maria Del Carmen Riesco-Martinez, Alberto Lens-Pardo, Carlos Carretero-Puche, Beatriz Rubio-Cuesta, Beatriz Soldevilla
Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are aggressive neoplasms of challenging clinical management. A small proportion of patients with early-stage disease may achieve long-term survival, but the majority of patients present with rapidly lethal metastatic disease. Current standard of care still follows the treatment paradigm of small cell lung cancer, a far more common G3 neuroendocrine neoplasm, although emerging molecular and clinical data increasingly question this approach...
July 11, 2023: Endocrine Reviews
Veronica Vella, Rosamaria Lappano, Eduardo Bonavita, Marcello Maggiolini, Robert Bryan Clarke, Antonino Belfiore, Ernestina Marianna De Francesco
In metabolic conditions such as obesity and diabetes, which are associated with deregulated signaling of the insulin/insulin-like growth factor system (IIGFs), inflammation plays a dominant role. In cancer, IIGFs is implicated in disease progression, particularly during obesity and diabetes; however, further mediators may act in concert with IIGFs to trigger meta-inflammation. The receptor for advanced glycation end-products (RAGE) and its ligands bridge together metabolism and inflammation in obesity, diabetes, and cancer...
July 11, 2023: Endocrine Reviews
Ningning Zhang, Mingyang Yuan, Jiqiu Wang
Classic hormone membrane receptors, such as leucine-rich repeat-containing G protein-coupled receptor (LGR) 1 (follicle-stimulating hormone receptor), LGR2 (luteinizing hormone receptor), and LGR3 (thyrotropin receptor), are crucial in endocrinology and metabolism, and the identification of new receptors can advance this field. LGR4 is a new member of this G protein-coupled receptor family and shows ways of expression and function similar to those of LGR1/2/3. Several recent studies have reported that, unlike LGR5/6, LGR4 plays essential roles in endocrine and metabolic diseases, including hypothalamic-gonadal axis defects, mammary gland dysplasia, osteoporosis, cardiometabolic diseases, and obesity...
July 11, 2023: Endocrine Reviews
Anvita Komarla, Suzanne Dufresne, Christina G Towers
Autophagy plays a complex role in several cancer types, including endocrine-dependent cancers, by fueling cellular metabolism and clearing damaged substrates. This conserved recycling process has a dual function across tumor types where it can be tumor suppressive at early stages but tumor promotional in established disease. This review highlights the controversial roles of autophagy in endocrine-dependent tumors regarding cancer initiation, tumorigenesis, metastasis, and treatment response. We summarize clinical trial results thus far and highlight the need for additional mechanistic, preclinical, and clinical studies in endocrine-dependent tumors, particularly in breast cancer and prostate cancer...
July 11, 2023: Endocrine Reviews
Jérôme Bertherat, Isabelle Bourdeau, Lucas Bouys, Fanny Chasseloup, Peter Kamenický, André Lacroix
Patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) usually present bilateral benign adrenocortical macronodules at imaging and variable levels of cortisol excess. PBMAH is a rare cause of primary overt Cushing's syndrome but may represent up to one-third of bilateral adrenal incidentalomas with evidence of cortisol excess. The increased steroidogenesis in PBMAH is often regulated by various G protein-coupled receptors (GPCRs) aberrantly expressed in PBMAH tissues; some receptor ligands are ectopically produced in PBMAH tissues, creating aberrant autocrine/paracrine regulation of steroidogenesis...
July 11, 2023: Endocrine Reviews
Cheryl A Conover, Claus Oxvig
Pregnancy-associated plasma protein-A PAPP-A) was first identified in the early 1970s as a placental protein of unknown function present at high concentrations in the circulation of pregnant women. In the mid-to-late 1990s, PAPP-A was discovered to be a metzincin metalloproteinase expressed by many non-placental cells that regulates local insulin-like growth factor (IGF) activity through cleavage of high-affinity IGF binding proteins (IGFBPs), in particular IGFBP-4. With PAPP-A as a cell surface-associated enzyme, the reduced affinity of the cleavage fragments results in increased IGF available to bind and activate IGF receptors in the pericellular environment...
June 2, 2023: Endocrine Reviews
Laura J Mauro, Angela Spartz, Julia R Austin, Carol A Lange
Ovarian cancer (OC) represents a collection of rare but lethal gynecologic cancers where the difficultly of early detection due to an often-subtle range of abdominal symptoms contributes to high fatality rates. With the exception of BRCA1/2 mutation carriers, OC most often manifests as a post-menopausal disease, a time in which the ovaries regress and circulating reproductive hormones diminish. Progesterone is thought to be a "protective" hormone that counters the proliferative actions of estrogen, as can be observed in the uterus or breast...
June 1, 2023: Endocrine Reviews
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