Frontiers of Hormone Research最新文献

North American and European authorities have identified thresholds up to 50 nmol/L serum 25-hydroxyvitamin D (25[OH]D) as optimal for pediatric vitamin D status. These recommendations are relative to skeletal endpoints, as vitamin D plays a pivotal role in bone mineral content (BMC) accretion. Suboptimal vitamin D consumption during youth may therefore hinder BMC acquisition, and contribute to an increased fracture risk. Though vitamin D requirements range between 400 and 800 IU/day, not all children achieve this. To encourage adequate vitamin D consumption, strategies such as supplementation, food labeling, and fortification, are currently being investigated. There is moderate support for the role of vitamin D supplementation on adolescent BMC accrual; however, factors such as age, maturation, population ancestry, and latitude, are not consistently accounted for across studies. Vitamin D is also linked with extraskeletal endpoints (e.g., muscle mass/function, adiposity, and metabolic health) in children, but the cross-sectional data do not necessarily align with results from experimental trials. Based on the evidence currently available, there is no need for a revision of the pediatric vitamin D recommendations at this time. Additional trials are required, however, to build upon the hypothesis-generating observational data, and to provide evidence for future vitamin D requirements across the globe.

The metabolic syndrome (MetS) is a conglomerate of clinical findings that convey into increased morbidity and mortality from type 2 diabetes mellitus (T2D) and cardiovascular disease. Hyperprolactinemia (hyperPRL) is associated with components of MetS, especially during pregnancy. Endogenous levels of sex steroids are high during pregnancy in contrast to untreated or replaced hypogonadism in most patients with a prolactinoma and hypogonadism may confer increased risk of MetS in hyperPRL. Dopamine-D2-agonist therapy can improve MetS in patients with a prolactinoma and lower glucose levels in patients with T2D. HyperPRL is a biomarker for decreased dopaminergic tonus in the hypothalamic-pituitary circuit. Patients with a prolactinoma, patients with schizophrenia and/or T2D often have disturbances in this balance and the finding of lower prolactin (PRL) levels in polycystic ovary syndrome (PCOS) may indicate increased dopaminergic tonus. Recent studies supported that PRL levels within or above reference range may be differently related to MetS. In healthy study populations and in PCOS, PRL levels were inversely associated with metabolic risk markers. Ongoing research on PRL fragments, vasoinhibins, may help explain some of the contradicting findings between prolactin levels and metabolism. Improved knowledge about MetS in hyperPRL can characterize subgroups of patients with hyperPRL, who would not otherwise be considered as candidates for dopamine-D2-agonist therapy such as patients with postpartum cardiomyopathy and postmenopausal women with T2D.

Classic endocrine feedback loops ensure the regulation of blood calcium. Calcium in the extracellular fluid (ECF) binds and activates the calcium sensing receptor (CaSR) on the parathyroid cells, leading to an increase in intracellular calcium. This in turn leads to a reduced parathyroid hormone (PTH) release. Hypocalcemia leads to the opposite sequence of events, namely, lowered intracellular calcium and increased PTH production and secretion. PTH rapidly increases renal calcium reabsorption and, over hours to days, enhances osteoclastic bone resorption and liberates both calcium and phosphate from the skeleton. PTH also increases fibroblast growth factor 23 (FGF23) release from mature osteoblasts and osteocytes. PTH stimulates the renal conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)2D, likely over several hours, which in turn will augment intestinal calcium absorption. Prolonged hypocalcemia and exposure to elevated PTH may also result in 1,25(OH)2D-mediated calcium and phosphorus release from bone. These effects restore the ECF calcium to normal and inhibit further production of PTH and 1,25(OH)2D. Additionally, FGF23 can be released from bone by 1,25(OH)2D and can in turn reduce 1,25(OH)2D concentrations. FGF23 has also been reported to decrease PTH production. When ECF calcium is in the hypercalcemic range, PTH secretion is reduced and renal 1,25(OH)2D production is decreased. In addition, the elevated calcium per se stimulates the renal CaSR, thus inducing calciuria. Therefore, suppression of PTH release and 1,25(OH)2D synthesis and stimulation of the renal CaSR lead to reduced renal calcium reabsorption, decreased skeletal calcium release, and decreased intestinal calcium absorption, resulting in the normalization of the elevated ECF calcium.

Diabetes is recognized as one of the most common acromegaly co-morbidities with a prevalence ranging 20-53%, while over one-third of these patients have an altered lipid profile. In fact, as in the non-acromegalic population, carbohydrate and lipid metabolism abnormalities are closely linked. Long term exposure to an excess of growth hormone (GH) and Insulin-like growth factor-1 concentrations results in insulin resistance and an increased hepatic glucose production. The lipolytic effect of GH results in the mobilization of free fatty acids that further contributes to the decreased insulin sensitivity found in these patients. Some studies suggest that the presence of diabetes contributes to the increased mortality of acromegaly, although this remains controversial. Successful treatment of acromegaly usually results in significant, albeit incomplete improvements of the abnormal metabolic profile.

Pharmacological glucocorticoid treatment is associated with adverse metabolic consequences such as hypertension, overweight, reduced glucose tolerance, diabetes mellitus and ultimately increased mortality in cardiovascular disease. Here we review the evidence of detrimental effects of hormone replacement therapy in adrenal insufficiency (AI). Registry studies indicate increased cardiovascular mortality, hypertension, diabetes, and dyslipidemia in both primary and secondary AI, but when cohorts with carefully characterized patients are studied the picture is less clear, and recently patients with primary AI was reported to have less hypertension and lower body mass index than controls. Whether near physiological replacement therapy increase long-term cardiovascular morbidity and mortality in AI is still unclear.

Cushing's syndrome (CS), including visceral obesity, dyslipidemia, hypertension and diabetes among its many manifestations, is "a model" of metabolic syndrome. Glucocorticoid (GC) excess, through a combination of effects on liver, muscle, adipose tissue and pancreas, increases gluconeogenesis and impairs insulin sensitivity, leading to carbohydrate abnormalities. Dyslipidemia is a common finding in CS as a consequence of GC-related increased lipolysis, lipogenesis and adipogenesis. CS patients experience typical changes in body composition, with fat redistribution resulting in accumulation of visceral adipose tissue. Hypertension, myocardial and vascular abnormalities along with the metabolic changes and the characteristic coagulopathy increase cardiovascular morbidity and mortality. Metabolic syndrome features can persist long after normalisation of cortisol levels.

Practical clinical guidance for vitamin D assessment and management relies on a strong evidence base, but unfortunately there are many deficiencies in our current knowledge. For the general population the Institute of Medicine recommendations are likely to provide adequate vitamin D levels without harms. Thus, most adults should ingest 600-800 IU (international units) in diet and supplements with up to 4,000 IU daily likely to be safe. In certain populations, such as those with osteoporosis or after bariatric surgery, it is important to know the levels of circulating 25-hydroxyvitamin D, but general screening has not been shown to improve health. One expert group has recommended a "reasonable" level of 30 ng/mL in those individuals for whom testing is required.