Breast cancer remains the most commonly diagnosed malignancy among women worldwide. While breast cancer treatment outcomes have improved in recent years there remains an unmet medical need for therapeutics that can be used with curative intent in the most aggressive breast cancer subtypes and for those cancers that have metastasized. In recent years, the success of T-cell-based therapies and other

Skeletal muscle insulin resistance (IR) is a critical deficiency in IR pathophysiology that significantly affects overall metabolic health. Skeletal muscle is mechanically sensitive since its structure and function are significantly influenced by factors, such as mechanical stretching and tissue stiffness. These mechanical stimuli can cause adaptive changes that enhance muscle performance and resilience

Pharmacotherapy involving hormones and hormone-derived molecules has various potential treatment targets. This includes addressing (partial) hormonal deficiencies, pursuing osteoanabolic effects, providing contraceptive options, or supporting gender-affirming transitions. In chronotherapy, the timing of the administration of active ingredients and different pharmaceutical forms is leveraged to maximize

Premature ovarian insufficiency (POI) is a highly heterogeneous reproductive disorder in both its etiology and clinical presentation. The epidemiological characteristics of POI suggest that its occurrence likely involves a combination of genetic and environmental factors. Deciphering the pathogenic mechanisms of POI is crucial for improving reproductive outcomes as well as managing the long-term complications

Parathyroid hormone (PTH)-related disorders have a major impact on bone metabolism and skeletal properties, due to the pivotal role of PTH in calcium and phosphate homeostasis and bone remodeling.Hyperparathyroidism is characterized by continuous exposure to excessive endogenous PTH, causing increased bone turnover in favor of bone resorption. Depending on the background of PTH overproduction, hyperparathyroidism

From antiquity, Man has been fascinated by at least two processes of testicular function: virility and reproduction; their biological basis was uncovered beginning in the mid-19th century. We have divided the search into 3 epochs: the speculative and observational, the experimental, and the biochemical/physiological. The first begins with Susruta, approximately 3,000 years ago and winds its way through

People with type 1 diabetes (T1D) are usually considered to exclusively exhibit β-cell failure, but they frequently also feature insulin resistance. This review discusses the mechanisms, clinical features, and therapeutic relevance of insulin resistance by focusing mainly on human studies using gold-standard techniques (euglycemic-hyperinsulinemic clamp). In T1D, tissue-specific insulin resistance

Oxytocin is a hypothalamic-posterior pituitary hormone with multiple effects, ranging from regulation of energy homeostasis to bone health and psychological wellbeing, in addition to its well-known effects in labor and lactation. Patients with hypothalamic and pituitary damage have a higher risk for medical and psychiatric comorbidities despite standard-of-care hormone replacement, and a clinically

Primary aldosteronism (PA), the most common cause of arterial hypertension, is surgically curable if a unilateral source of the hyperaldosteronism is discovered. To identify the patients who are curable, all current guidelines recommend adrenal venous sampling (AVS), a procedure which, albeit simple in principle, remains scarcely available and markedly under-utilized, because it is still perceived

Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid hormone that is synthesized and released from upper intestinal enteroendocrine K-cells in response to the ingestion of glucose or fat. The structure of GIP places it in the secretin/vasoactive intestinal polypeptide family of gastrointestinal regulatory peptides. Although originally named "gastric inhibitory polypeptide" on the basis

Lifestyle interventions are the cornerstone of obesity treatment. However, insufficient long-term effects are observed in patients with genetic obesity disorders, as their hyperphagia remains untreated. Hence, patients with genetic obesity often require additional pharmacotherapy to effectively manage and treat their hyperphagia and obesity. Recent advancements in antiobesity pharmacotherapy have expanded

Klinefelter Syndrome (KS) is caused by the presence of a supernumerary X-chromosome (conferring the classical 47,XXY karyotype) and is the commonest sex chromosome abnormality in men. The clinical features described in the early characterisation of the syndrome include tall stature, small testes, hypogonadism, gynecomastia and neurodevelopmental deficits. However, the syndrome presents a broad phenotypic

There has been significant progress in understanding the molecular landscape of pediatric differentiated thyroid carcinoma (DTC) over the past 2 decades. Classification of pediatric DFC into 3 tiers, RAS-like mutant, BRAF mutant, and kinase fusions, accurately reflects an increasing risk for invasive behavior, including regional and distant metastasis. In clinical practice, somatic oncogene testing

Primary mitochondrial disorders (PMD) are genetic disorders affecting the structure or function of the mitochondrion. Mitochondrial functions are diverse, including energy production, ion homeostasis, reactive oxygen species regulation, antioxidant defense, and biosynthetic responsibilities, notably including steroidogenesis. Mitochondria provide the energy to drive intracellular production and extracellular

Vitamin D deficiency during pregnancy is associated with an increased risk of health issues in the offspring. Accordingly, recent Endocrine Society guidelines strongly support supplementation in pregnancy, also underlining that without consensus on optimal maternal vitamin D levels, routine screening is currently irrelevant. Knowledge of organ-specific effects of vitamin D and its association with

Obesity is a major global concern and is generally attributed to a combination of genetic and environmental factors. Several hypotheses have been proposed to explain the evolutionary origins of obesity epidemic, including thrifty and drifty genotypes, and changes in thermogenesis. Here, we put forward the hypothesis of metaflammation, which proposes that due to intense selection pressures exerted by

Discovered in 1996, PCSK7 is the seventh of the 9-membered proprotein convertase subtilisin-kexin (PCSK) family. This article reviews the various aspects of the multifaceted biology of PCSK7 and what makes it an exciting new target for metabolic dysfunction-associated steatotic liver disease (MASLD), affecting ∼30% of the population globally, dyslipidemia, cardiovascular disease, and likely cancer/metastasis

Growth hormone (GH) is a pituitary-derived endocrine hormone required for normal postnatal growth and development. Hypo- or hypersecretion of endocrine GH results in 2 pathologic conditions, namely GH deficiency (GHD) and acromegaly. Additionally, GH is also produced in nonpituitary and tumoral tissues, where it acts rather as a cellular growth factor with an autocrine/paracrine mode of action. An

The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal

There is strong evidence that IGF signaling is involved in fundamental aspects of the aging process. However, the extracellular part of the IGF system is complex with various receptors, ligand effectors, high-affinity IGF-binding proteins, proteinases, and endogenous inhibitors that all, along with their biological context, must be considered. The IGF system components are evolutionarily conserved

Papillary craniopharyngioma (PCP) is a rare type of tumor, comprising ∼20% of all craniopharyngioma (CP) cases. It is now recognized as a separate pathological entity from the adamantinomatous type. PCPs are benign tumors, classified as World Health Organization grade 1, characterized by nonkeratinizing squamous epithelium. They typically grow as solid and round papillomatous masses or as unilocular

Treatment of classic congenital adrenal hyperplasia (CAH) is directed at replacing deficient hormones and reducing androgen excess. However, even in the era of early diagnosis and lifelong hormonal substitution, the presence of CAH is still associated with numerous complications and also with increased mortality. The aim of this article was to create an authoritative and balanced review concerning

The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to

In healthy individuals, the majority of cortisol secretion occurs within several hours surrounding morning awakening. A highly studied component of this secretory period is the cortisol awakening response (CAR), the rapid increase in cortisol levels across the first 30 to 45 minutes after morning awakening. This strong cortisol burst at the start of the active phase has been proposed to be functional

Somatostatin analogs, such as octreotide, lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly. These ligands are also used as important molecules for radiation therapy and imaging of neuroendocrine tumors. Somatostatin receptors (SSTRs) are canonical G protein-coupled proteins that play a role in metabolism, growth

Adiponectin is an abundantly secreted hormone that communicates information between the adipose tissue, and the immune and cardiovascular systems. In metabolically healthy individuals, adiponectin is usually found at high levels and helps improve insulin responsiveness of peripheral tissues, glucose tolerance, and fatty acid oxidation. Beyond its metabolic functions in insulin-sensitive tissues, adiponectin

The parasellar region is the anatomical area around the sella turcica that represents a crucial crossroad for important adjacent structures. Several distinct tumors can primarily originate from this area, the most common being meningiomas, gliomas, embryonal cell tumors, germ cell tumors, and craniopharyngiomas. In addition, a number of systemic and inflammatory disorders can also affect the parasellar

Glucocorticoids exert pleiotropic effects on all tissues to regulate cellular and metabolic homeostasis. Synthetic forms are used therapeutically in a wide range of conditions for their anti-inflammatory benefits, at the cost of dose and duration-dependent side effects. Significant variability occurs between tissues, disease states, and individuals with regard to both the beneficial and deleterious

From 1965 to 2015, immense strides were made into understanding the mechanisms underlying the common androgen excess disorders, premature adrenarche and polycystic ovary syndrome (PCOS). The author reviews the critical discoveries of this era from his perspective investigating these disorders, commencing with his early discoveries of the unique pattern of plasma androgens in premature adrenarche and

There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second-termed "mini-puberty"-in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells from adrenal medullary chromaffin tissues and extra-adrenal paraganglia, respectively. Although the current treatment for PPGLs is surgery, optimal treatment options for advanced and metastatic cases have been limited. Hence, understanding the role of the immune system in PPGL tumorigenesis can

Preclinical models (typically ovariectomized rats and genetically altered mice) have underpinned much of what we know about skeletal biology. They have been pivotal for developing therapies for osteoporosis and monogenic skeletal conditions, including osteogenesis imperfecta, achondroplasia, hypophosphatasia, and craniodysplasias. Further therapeutic advances, particularly to improve cortical strength

The treatment of polycystic ovary syndrome (PCOS) faces challenges as all known treatments are merely symptomatic. The US Food and Drug Administration has not approved any drug specifically for treating PCOS. As the significance of genetics and epigenetics rises in drug development, their pivotal insights have greatly enhanced the efficacy and success of drug target discovery and validation, offering

Mouse models of growth hormone deficiency (GHD) have provided important tools for uncovering the various actions of GH. Nearly 100 years of research using these mouse lines has greatly enhanced our knowledge of the GH/IGF-1 axis. Some of the shared phenotypes of the 5 "common" mouse models of GHD include reduced body size, delayed sexual maturation, decreased fertility, reduced muscle mass, increased

Thyroid eye disease (TED) is the most common extra thyroidal manifestation of Graves' disease (GD). It may also present in those who are hypothyroid or euthyroid. The characteristic clinical manifestations of TED, chemosis, lid swelling, proptosis, and diplopia, are driven by a combination of inflammation and extracellular matrix modification. It has recently emerged that 1 of the major drivers of

Glucocorticoid (GC) hormones are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and insufficient GC associated with adverse effects on health. Current assessment of GC status is primarily clinical, often in conjunction with serum cortisol values, which may be stimulated or suppressed depending on the GC disturbance being

Receptor guanylyl cyclases (GCs) are single membrane spanning, multidomain enzymes, that synthesize cGMP in response to natriuretic peptides or other ligands. They are evolutionarily conserved from sea urchins to humans and regulate diverse physiologies. Most family members are phosphorylated on 4 to 7 conserved serines or threonines at the beginning of their kinase homology domains. This review describes

Basal insulin continues to be a vital part of therapy for many people with diabetes. First attempts to prolong the duration of insulin formulations were through the development of suspensions that required homogenization prior to injection. These insulins, which required once- or twice-daily injections, introduced wide variations in insulin exposure contributing to unpredictable effects on glycemia

Midgut neuroendocrine neoplasms (NENs) are one of the most common subtypes of NEN, and their incidence is rising globally. Despite being the most frequently diagnosed malignancy of the small intestine, little is known about their underlying molecular biology. Their unusually low mutational burden compared to other solid tumors and the unexplained occurrence of multifocal tumors makes the molecular

Our overview covers several key areas related to recent results obtained for collagen type VI and endotrophin (ETP). (1) An introduction to the history of ETP, including how it was identified, how it is released, and its function and potential receptors. (2) An introduction to the collagen family, with a focus on what differentiates collagen type VI from an evolutionary standpoint. (3) An overview

Pituitary gigantism is a rare manifestation of chronic growth hormone (GH) excess that begins before closure of the growth plates. Nearly half of pituitary gigantism patients have an identifiable genetic cause. X-linked acrogigantism (X-LAG; 10% of pituitary gigantism) typically begins during infancy and can lead to the tallest individuals described. In the 10 years since its discovery, about 40 patients

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites

Elite individual sports in which success depends on power, speed or endurance are conventionally divided into male and female events using traditional binary definitions of sex. Male puberty creates durable physical advantages due to the 20-30-fold increase in circulating testosterone producing a sustained uplift in men's muscle, bone, hemoglobin, and cardiorespiratory function resulting from male

Multiple changes occur in hormonal regulation with aging and across various endocrine organs. These changes are associated with multiple age-related disorders and diseases. A better understanding of responsible underling biological mechanisms could help in the management of multiple endocrine disorders over and above hormone replacement therapy (HRT). Cellular senescence is involved in multiple biological

Research on lean, energy-deficient athletic and military cohorts has broadened the concept of the Female Athlete Triad into the Relative Energy Deficiency in Sport (REDs) syndrome. REDs represents a spectrum of abnormalities induced by low energy availability (LEA), which serves as the underlying cause of all symptoms described within the REDs concept, affecting exercising populations of either biological

Carcinoid syndrome (CS) is a debilitating disease that affects approximately 20% of patients with neuroendocrine neoplasms (NEN). Due to the increasing incidence and improved overall survival of patients with NEN over recent decades, patients are increasingly suffering from chronic and refractory CS symptoms. At present, symptom control is hampered by an incomplete understanding of the pathophysiology

Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques have allowed us to elucidate various components of the intricate neurocircuitry governing appetite and weight regulation connecting the hypothalamus, pituitary gland, brainstem, adipose tissue, pancreas, and gastrointestinal tract. On a

Adipose tissue is the largest endocrine organ and an accepted contributor to overall energy homeostasis. There is strong evidence linking increased adiposity to the development of 13 types of cancer. With increased adiposity comes metabolic dysfunction and insulin resistance, and increased systemic insulin and glucose support the growth of many cancers, including those of the colon and endometrium

Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review

This review analyzes the published evidence regarding maternal factors that influence the developmental programming of long-term adiposity in humans and animals via the central nervous system (CNS). We describe the physiological outcomes of perinatal underfeeding and overfeeding and explore potential mechanisms that may mediate the impact of such exposures on the development of feeding circuits within

Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of microvascular and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid

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 a major public health problem. The causes of age-related cognitive impairment are multiple, complex, and difficult to determine. However, type 2 diabetes (T2D) is linked to an enhanced

Over the past 4 decades, the clinical care of people living with HIV (PLWH) evolved from treatment of acute opportunistic infections to the management of chronic, noncommunicable 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

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with 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 nonsurgical candidates

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

The homeostasis of bone microenvironment is the foundation of bone health and comprises 2 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 the sympathetic nervous system, involving neurotransmitters like serotonin and norepinephrine

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

Mitochondria sense both biochemical and energetic input in addition to communicating signals regarding the energetic state of the cell. Increasingly, these signaling organelles are recognized as key for regulating different cell functions. This review summarizes recent advances in mitochondrial communication in striated muscle, with specific focus on the processes by which mitochondria communicate