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Endocrine Reviews

Pratik B Sandesara, Salim S Virani, Sergio Fazio, Michael D Shapiro
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is a well-established mediator of atherosclerosis and a key target for intervention for the primary and secondary prevention of ASCVD. However, despite significant reduction in LDL-C, patients continue to have recurrent ASCVD events. Hypertriglyceridemia maybe an important contributor of this residual risk. Observational and genetic epidemiological data strongly support a causal role of triglycerides and the cholesterol content within triglyceride-rich lipoproteins (TGRL) and/or remnant cholesterol (RC) in the development of ASCVD...
October 11, 2018: Endocrine Reviews
Paishiun N Hsieh, Liyan Fan, David R Sweet, Mukesh K Jain
Nutrient handling by higher organisms is a complex process that is regulated in a significant manner at the transcriptional level. Studies over the past 15 years highlight the critical importance of a family of transcriptional regulators termed the Krüppel-like factors (KLFs) in metabolism. Within an organ, distinct KLFs direct networks of metabolic gene targets to achieve specialized functions. This regulation is often orchestrated in concert with recruitment of tissue-specific transcriptional regulators, particularly members of the nuclear receptor family...
October 10, 2018: Endocrine Reviews
Guy T'Sjoen, Jon Arcelus, Louis Gooren, Daniel T Klink, Vin Tangpricha
Gender affirming treatment for transgender people requires a multidisciplinary approach in which endocrinologists play a crucial role. The aim of this paper is to review recent data on hormonal treatment of this population and its effect on physical, psychological and mental health. The Endocrine Society guidelines for transgender women include estrogens in combination with androgen lowering medications. Feminizing treatment with estrogens and anti-androgens has desired physical changes, such as enhanced breast growth, reduction of facial and body hair growth and fat redistribution in a female pattern...
October 10, 2018: Endocrine Reviews
Helen L Storr, Sumana Chatterjee, Louise A Metherell, Corinne Foley, Ron G Rosenfeld, Philippe F Backeljauw, Andrew Dauber, Martin O Savage, Vivian Hwa
GH insensitivity (GHI) presents in childhood with growth failure and in its severe form is associated with extreme short stature, dysmorphic and metabolic abnormalities. In recent years, the clinical, biochemical and genetic characteristics of GHI and other overlapping short stature syndromes have rapidly expanded. This can be attributed to advancing genetic techniques and a greater awareness of this group of disorders. We review this important spectrum of defects, which present with phenotypes at the milder end of the GHI continuum...
September 27, 2018: Endocrine Reviews
Gidon J Bönhof, Christian Herder, Alexander Strom, Nikolaos Papanas, Michael Roden, Dan Ziegler
Diabetic neuropathy, with its major clinical sequels notably neuropathic pain, foot ulcers, and autonomic dysfunction, is associated with substantial morbidity, increased risk of mortality, and reduced quality of life. Despite its major clinical impact, diabetic neuropathy remains underdiagnosed and undertreated. Moreover, the evidence supporting a benefit for causal treatment is weak at least in patients with type 2 diabetes, and current pharmacotherapy is largely limited to symptomatic treatment options. Thus, a better understanding of the underlying pathophysiology is mandatory for translation into new diagnostic and treatment approaches...
September 25, 2018: Endocrine Reviews
Laura van Iersel, Karen E Brokke, Roger A H Adan, Lauren C M Bulthuis, Erica L T van den Akker, Hanneke M van Santen
The development of hypothalamic obesity (HO) following craniopharyngioma (CP) and other suprasellar tumors leads to reduced patient quality of life. No treatment algorithms are currently available for management of HO. Depending on which hypothalamic nuclei are destroyed, the pathophysiologic mechanisms and clinical symptoms that contribute to HO differ among patients. Here, we review the contribution of the hypothalamus to the pathophysiologic mechanisms and symptoms underlying CP-associated HO. In addition, we performed a systematic search of MEDLINE and Embase to identify all intervention studies for weight management in patients with CP or other suprasellar tumors published until September 2017...
September 20, 2018: Endocrine Reviews
José Cipolla-Neto, Fernanda Gaspar do Amaral
Melatonin is a ubiquitous molecule present in almost every live being from bacteria to humans. In vertebrates, besides being produced in peripheral tissues and acting as an autocrine and paracrine signal, melatonin is centrally synthetized by a neuroendocrine organ, the pineal gland. Independently of the considered specie, pineal hormone melatonin is always produced during the night and its production and secretory episode duration is directly dependent on the length of the night. As its production is tightly linked to the light/dark cycle, melatonin main hormonal systemic integrative action is to coordinate behavioral and physiological adaptations to the environmental geophysical day and season...
September 12, 2018: Endocrine Reviews
Terry J Smith, Joseph A M J L Janssen
Thyroid-associated ophthalmopathy (TAO) is a complex disease process presumed to emerge from autoimmunity occurring in the thyroid gland, most frequently in Graves' disease (GD). It is disfiguring and potentially blinding, culminating in orbital tissue remodeling and disruption of function of structures adjacent to the eye. There are currently no medical therapies proven capable of altering the clinical outcome of TAO in randomized, placebo-controlled multicenter trials. The orbital fibroblast represents the central target for immune reactivity...
September 11, 2018: Endocrine Reviews
Lee-Shing Chang, Romualdo Barroso-Sousa, Sara M Tolaney, F Stephen Hodi, Ursula B Kaiser, Le Min
Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Targeting the immune checkpoints CTLA-4 and PD-1 with inhibitory antibodies has demonstrated effective and durable anti-tumor activity in subgroups of cancer patients. The United States Food and Drug Administration has approved several immune checkpoint inhibitors (ICPis) for the treatment of a broad spectrum of malignancies. Endocrinopathies have emerged as one of the most common immune-related adverse events (irAEs) of ICPi therapy...
September 3, 2018: Endocrine Reviews
Mônica R Gadelha, Leandro Kasuki, Dawn St Lim, Maria Fleseriu
Acromegaly is a chronic systemic disease with many complications and is associated with increased mortality when not adequately treated. Significant advances in acromegaly treatment, as well as in the treatment of many of its complications, mainly diabetes mellitus, heart failure and arterial hypertension, were achieved in the last decades. These developments allowed change in both prevalence and severity of some acromegaly complications and furthermore resulted in a reduction of mortality. Nowadays, mortality seems to be similar to the general population in adequately treated patients with acromegaly...
August 31, 2018: Endocrine Reviews
Ian R Reid, Paul A Baldock, Jillian Cornish
Leptin originates in adipocytes, including those in bone marrow and circulates in concentrations 20- 90-fold higher than those in the cerebrospinal fluid. It has direct anabolic effects on osteoblasts and chondrocytes, but also influences bone indirectly: via the hypothalamus and sympathetic nervous system, via changes in body weight, and via effects on the production of other hormones (e.g. pituitary). Leptin's role in bone physiology is determined by the balance of these conflicting effects. Reflecting this inconsistency, the leptin-deficient mouse has reduced length and bone mineral content of long bones, but increased vertebral trabecular bone...
August 31, 2018: Endocrine Reviews
Dennis M Black, Bo Abrahamsen, Mary L Bouxsein, Thomas Einhorn, Nicola Napoli
Bisphosphonates (BPs) are highly effective in treating osteoporosis and reduce hip, vertebral and other fractures by as much as 50-70%. However, since 2006, atypical femur fractures (AFF) emerged as potential side effects of BPs and other treatments. These fractures have unusual radiologic features and occur with little trauma. Public concern has led to a >50% decrease in BP usage. However, AFF are rare: for each AFF, over 1200 fractures, including 135 hip fractures, are prevented. Case-definition criteria were updated by the ASBMR in 2014...
August 29, 2018: Endocrine Reviews
Pureum Kim, Henrik Oster, Hendrik Lehnert, Sebastian M Schmid, Nicole Salamat, Johanna L Barclay, Erik Maronde, Warrick Inder, Oliver Rawashdeh
A plethora of physiological processes show stable and synchronized daily oscillations that are either driven or modulated by biological clocks. A circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the ventral hypothalamus coordinates 24-hour oscillations of central and peripheral physiology with the environment. The circadian clockwork involved in driving rhythmic physiology is composed of various clock genes that are interlocked via a complex feedback loop to generate precise yet plastic oscillations of about 24-hours...
August 28, 2018: Endocrine Reviews
Pouneh K Fazeli, Anne Klibanski
Anorexia nervosa is a psychiatric disease characterized by a low-weight state due to self-induced starvation. This disorder, which predominantly affects women, is associated with hormonal adaptations which minimize energy expenditure in the setting of low nutrient intake. These adaptations include growth hormone resistance, functional hypothalamic amenorrhea and non-thyroidal illness syndrome. Although these adaptations may be beneficial to short-term survival, they contribute to the significant and often persistent morbidity associated with this disorder, including bone loss which affects over 85% of women...
August 27, 2018: Endocrine Reviews
Trevor M Penning, Phumvadee Wangtrakuldee, Richard J Auchus
Aldo-keto reductases (AKRs) are monomeric NAD(P)(H) dependent oxidoreductases that play pivotal roles in the biosynthesis and metabolism of steroids in humans. AKR1C enzymes acting as 3-keto-, 17-keto- and 20-keto-steroid reductases are involved in the pre-receptor regulation of ligands for the androgen, estrogen and progesterone receptor and are considered drug targets to treat steroid hormone dependent malignancies and endocrine disorders. By contrast AKR1D1 is the only known steroid 5β-reductase and is essential for bile-acid biosynthesis, the generation of ligands for the farnesoid-X-receptor, and the 5β-dihydrosteroids that have their own biological activity...
August 20, 2018: Endocrine Reviews
Anand Vaidya, Paolo Mulatero, Rene Baudrand, Gail K Adler
Primary aldosteronism is characterized by aldosterone secretion that is independent of renin and angiotensin II and sodium status. The deleterious effects of primary aldosteronism are mediated by excessive activation of the mineralocorticoid receptor that results in the well-known consequences of volume expansion, hypertension, hypokalemia, and metabolic alkalosis, but also increases the risk for cardiovascular and kidney disease, and death. For decades, the approaches to defining, diagnosing, and treating primary aldosteronism have been relatively constant and generally focused on detecting and treating the more severe presentations of the disease...
August 15, 2018: Endocrine Reviews
Emmanuel Somm, François R Jornayvaz
Discovered 20 years ago, Fibroblast Growth Factor (FGF) 19, and its mouse ortholog FGF15, were the first members of a new subfamily of FGFs able to act as hormones. During fetal life, FGF15/19 is involved in organogenesis, affecting the development of the ear, eye, heart and brain. At adulthood, FGF15/19 is mainly produced by the ileum, acting on the liver to repress hepatic bile acid synthesis and promote postprandial nutrient partitioning. In rodents, pharmacologic doses of FGF19 induce the same anti-obesity and anti-diabetic actions as FGF21, these metabolic effects being partly mediated by the brain...
August 14, 2018: Endocrine Reviews
Karen D Corbin, Kimberly A Driscoll, Richard E Pratley, Steven R Smith, David M Maahs, Elizabeth J Mayer-Davis
There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and pathogenesis of type 1 diabetes. Emerging evidence suggests that obesity contributes to insulin resistance, dyslipidemia and cardiometabolic complications in type 1 diabetes. Unique therapeutic strategies may be required to address these comorbidities within the context of intensive insulin therapy, which promotes weight gain...
July 27, 2018: Endocrine Reviews
Nadia Bougarne, Basiel Weyers, Sofie J Desmet, Julie Deckers, David W Ray, Bart Staels, Karolien De Bosscher
Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor of clinical interest as a drug target in various metabolic disorders. PPARα also exhibits marked anti-inflammatory capacities. The first-generation PPARα agonists, the fibrates, have however been hampered by drug-drug interaction issues, statin drop-in, and ill-designed cardiovascular intervention trials. Notwithstanding, understanding the molecular mechanisms by which PPARα works will enable control of its activities as a drug target for metabolic diseases with an underlying inflammatory component...
October 1, 2018: Endocrine Reviews
Ali Abbara, Sophie A Clarke, Waljit S Dhillo
Infertility affects one in six of the population and increasingly couples require treatment with assisted reproductive techniques. In vitro fertilization (IVF) treatment is most commonly conducted using exogenous FSH to induce follicular growth and human chorionic gonadotropin (hCG) to induce final oocyte maturation. However, hCG may cause the potentially life-threatening iatrogenic complication "ovarian hyperstimulation syndrome" (OHSS), which can cause considerable morbidity and, rarely, even mortality in otherwise healthy women...
October 1, 2018: Endocrine Reviews
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