Endocrine reviews最新文献

Klinefelter syndrome (KS) is caused by the presence of a supernumerary X chromosome (conferring the classical 47,XXY karyotype) and is the most common sex chromosome abnormality in men. The clinical features described in the early characterization of the syndrome include tall stature, small testes, hypogonadism, gynecomastia, and neurodevelopmental deficits. However, the syndrome presents a broad phenotypic spectrum that seems to be evolving, along with environmental and general health changes. Although a proportion of men with KS are asymptomatic, others experience numerous severe comorbidities, ranging from cardiovascular to autoimmune disorders. Once considered a hallmark of the syndrome, the inability to conceive can now be overcome with assisted reproductive technology. The neuropsychological stigmata, once overstated, thereafter inadvertently dismissed, now demand a more balanced and objective approach. Significant advances have been made in our understanding of KS over recent years, including the molecular machinery involved in the chromosomal disjunction that gives rise to the syndrome. Our understanding of the risk-benefit of testosterone replacement therapy has greatly improved; however, many gaps persist. Future work should be prioritized according to the needs of people with KS. There are opportunities for new research addressing the fields of fertility, cardiovascular prevention, neurodevelopment, quality of life, and bone health. Above all, solid registries and extensive prospective longitudinal studies are needed to enroll people with KS to determine their evolving needs as they progress through their lifespan. These studies would be best initiated with international collaboration to ensure the results apply to all those with this condition worldwide.

From antiquity, man has been fascinated by at least 2 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 3000 years ago, and winds its way through the Greek, Roman, the Christian Bible, Arabic, Chinese, and Indian pathways before coalescing in Europe at the dawn of the Renaissance. The second began with. Thomas Willis, who postulated a virilizing factor from the testis. A century later de Bordeu hypothesized a neurosecretory function for the hypothalamus/pituitary. After John Hunter began to study testis implantation, it was Berthold who showed a secretory function of the testis following implantation. Charles-Éduard Brown-Séquard focused the medical and lay communities on testis secretion with self-experimentation with animal testis extracts leading to more than 4 decades of uncertainty in the newly launched science of endocrinology. Multiple series of testicular implants and vas deferens ligations for the purposes of rejuvenation of older men followed. The medical experimentation continued in the biochemical/physiological epoch where androgenic steroids were isolated, purified, identified, synthesized, and used in clinical trials. The effects of castration, some known from antiquity, were placed on a modern scientific basis with studies of the Skoptzy, a self-castrating sect from Russia and the castrati opera singers. Details of hypothalamic-pituitary-gonadal axis function as well as the embryology of male sexual differentiation and spermatogenesis were defined during this epoch.

Primary aldosteronism (PA), the most common cause of arterial hypertension, is surgically curable if a unilateral source of the hyperaldosteronism is discovered. To identify which patients are curable, all current guidelines recommend adrenal venous sampling (AVS), a procedure which, albeit simple in principle, remains scarcely available and markedly underutilized, because it is still perceived as technically challenging, invasive, and difficult to interpret. The lack of uniformly accepted standards for performance and interpretation of AVS, alongside the diffuse concerns that (although quite rarely) it can be complicated by adrenal vein rupture, contribute to the scant utilization of AVS. In the last decade, several major studies have led to a greater understanding of the use of AVS in PA patients, thus paving the way to a more rational and effective application that can enable diagnosis of many more PA patients with a unilateral form of the disease to be referred for curative adrenalectomy. Moreover, microcatheters and androstenedione have been introduced to increase the success rate. This review provides updated information on the subtyping of PA by means of AVS and examines key issues on the selection and preparation of patients, the optimal performance of the procedure, and the interpretation of its results for diagnostic purposes, even in the most challenging cases. Situations when AVS can be omitted before surgery and alternative functional imaging techniques that have been proposed to identify unilateral surgical curable PA to circumvent the bottleneck represented by the limited availability of AVS worldwide, are also discussed.

Oxytocin (OXT) is a hypothalamic-posterior pituitary hormone with multiple effects, ranging from regulation of energy homeostasis to bone health and psychological well-being, in addition to its well-known effects on 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 relevant OXT-deficient state has been identified in patients with arginine vasopressin deficiency (formerly known as central diabetes insipidus) in the last decade. Therefore, OXT deficiency in patients with hypothalamic and pituitary damage is an emerging field. While intranasal oxytocin is readily available to patients, it is not Food and Drug Administration approved in the United States and the quality of compounded formulations is unclear. In addition, more research is needed to establish the safety and efficacy of OXT-based therapeutics in patients with hypothalamic and pituitary damage before recommending treatment. This review summarizes the current knowledge of the OXT system, OXT deficiency in other clinical conditions, and relevance to patients with hypothalamic and pituitary damage. We highlight emerging data supporting OXT deficiency in hypothalamic-pituitary disease, diagnostic challenges, development of therapeutic strategies, and future research directions to advance the field.

PTH-related disorders have a major impact on bone metabolism and skeletal properties because of 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 is divided into primary, secondary, and tertiary hyperparathyroidism. The clinical presentation varies from deterioration of bone microarchitecture and decreased bone mineral density to profound bone involvement, such as osteitis fibrosa cystica and fragility fractures. Although successful parathyroidectomy represents the definitive treatment and may promote regression of most of the skeletal defects, the medical approach of calcimimetics and antiresorptive agents is a promising alternative in cases where parathyroidectomy is not feasible or unsuccessful. Hypoparathyroidism is the pathophysiological counterpart of hyperparathyroidism and also leads to disorders of bone metabolism and structure. Chronic PTH deprivation is associated with low bone remodeling and increased bone mineral density. The defective microarchitecture might affect bone strength and raise the risk for adverse skeletal events. Recombinant human PTH acts as a replacement therapy and is safe and efficient in restoring calcium/phosphate homeostasis and bone turnover. However, it is approved only for refractory cases, as conventional management with calcium and active vitamin D remains the first-line treatment. This article reviews the skeletal involvement in the most frequent parathyroid disorders, hyperparathyroidism and hypoparathyroidism, and rare familial disorders of PTH metabolism, as assessed by clinical, laboratory, and imaging parameters, and the effect of the available treatment strategies.

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 of its ability to inhibit gastric acid secretion, GIP accounts for 60% to 80% of the postprandial insulin response, consistent with the notion that this regulatory peptide constitutes the principal physiological incretin. Under normal conditions, GIP plays a major role in nutrient deposition and storage, both directly through its insulin-mimetic properties and indirectly by enhancing insulin release. GIP is overexpressed in obese individuals, which may exacerbate insulin resistance manifested by many patients with type 2 diabetes mellitus. Enhanced postprandial secretion of GIP also initiates a vicious cycle characterized by increased nutrient uptake and storage in adipocytes, leading to insulin resistance and hyperinsulinemia, which then further increases adipocyte nutrient uptake and storage. Despite the deleterious consequences of GIP overexpression, when combined with glucagon-like peptide-1 analogues, GIP agonism has been demonstrated to provide benefit in treating obesity by mechanisms currently not fully elucidated. In contrast, consistent with the etiologic role of GIP overexpression in the pathogenesis of obesity, both genetic abrogation and immunoneutralization of GIP signaling have been shown to reduce the development of obesity in preclinical models. Whether these beneficial effects of GIP antagonism will be extended to humans needs to be determined.

Skin is the largest organ of the human body and undergoes both intrinsic (chronological) and extrinsic aging. While intrinsic skin aging is driven by genetic and epigenetic factors, extrinsic aging is mediated by external threats such as UV irradiation or fine particular matters, the sum of which is referred to as exposome. The clinical manifestations and biochemical changes are different between intrinsic and extrinsic skin aging, albeit overlapping features exist, eg, increased generation of reactive oxygen species, extracellular matrix degradation, telomere shortening, increased lipid peroxidation, or DNA damage. As skin is a prominent target for many hormones, the molecular and biochemical processes underlying intrinsic and extrinsic skin aging are under tight control of classical neuroendocrine axes. However, skin is also an endocrine organ itself, including the hair follicle, a fully functional neuroendocrine "miniorgan." Here we review pivotal hormones controlling human skin aging focusing on IGF-1, a key fibroblast-derived orchestrator of skin aging, of GH, estrogens, retinoids, and melatonin. The emerging roles of additional endocrine players, ie, α-melanocyte-stimulating hormone, a central player of the hypothalamic-pituitary-adrenal axis; members of the hypothalamic-pituitary-thyroid axis; oxytocin, endocannabinoids, and peroxisome proliferator-activated receptor modulators, are also reviewed. Until now, only a limited number of these hormones, mainly topical retinoids and estrogens, have found their way into clinical practice as anti-skin aging compounds. Further research into the biological properties of endocrine players or its derivatives may offer the development of novel senotherapeutics for the treatment and prevention of skin aging.

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 secretion of all hormones. The understanding of the endocrine consequences of PMD is key to timely identification of both endocrine complications in PMD patients, and PMD presenting primarily with endocrine disease. This is a narrative review on the endocrine manifestations of PMD, underlying disease mechanisms, and current and emerging approaches to diagnosing and treating these complex disorders. Diabetes is the most frequent endocrine manifestation of PMD, but growth hormone deficiency, adrenal insufficiency, hypogonadism, and parathyroid dysfunction may occur. Despite the intricate involvement of the thyroid gland in metabolic regulation, there is little evidence for a causal relationship between thyroid dysfunction and PMD. In conclusion, endocrine dysfunction is observed in PMD with varying incidence depending on the specific mitochondrial disorder and the endocrine organ in question. Diagnosis of PMD in a patient with endocrine-presenting features requires a high level of clinical suspicion, particularly when apparently unrelated comorbidities co-exist. Similarly, endocrine pathology may be subtle in patients with known PMD, and thorough consideration must be given to ensure timely diagnosis and treatment. The scope for novel therapeutics for this group of devastating conditions is enormous; however, several challenges remain to be overcome before hopes of curative treatments can be brought into clinical practice.