RESUMEN

Antiresorptive agents for treating postmenopausal osteoporosis include selective estrogen receptor modulator (SERM), bisphosphonates and denoumab. Teriparatide is the only Food and Drug Administration-approved anabolic agent. Synergistic effects of combining teriparatide with an antiresorptive agent have been proposed and studied. This article reviews the trial designs and the outcomes of combination therapies. Results of the combination therapy for teriparatide and bisphosphonates were mixed; while small increases of bone density were observed in the combination therapy of teriparatide and estrogen/SERM and that of teriparatide and denosumab. Those clinical studies were limited by small sample sizes and lack of fracture outcomes.

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVE: Although the use of oral cholecystographic agents (OCAs) had declined due to limited availability, there is literature to suggest it is an effective medication for thyrotoxicosis in appropriate clinical situations. METHODS: The authors performed a PubMed search and systematically reviewed all the English written case reports, original studies and reviews from 1953 to 2012. Additional information was supplemented from available online pharmacologic databases. RESULTS: The off-label use of OCAs was reviewed for the management of neonatal and adult Graves' disease, subacute thyroiditis, amiodarone-induced thyroiditis (AIT), exogenous hyperthyroidism, toxic multinodular goiter (TMNG), thyrotropinoma, thyrotoxicosis during pregnancy, rapid pre-operative control of hyperthyroidism, and thyroid storm. Adverse effects were also reviewed. CONCLUSION: OCAs generally are effective agents in treating thyrotoxicosis in the etiologies reviewed. OCAs are clinically relevant in patients who require rapid control, such as in the pre-operative state or patient who cannot tolerate a thyrotoxicosis state. OCA may also be beneficial in situations where other anti-thyroidal medication would be hazardous or ineffective, such as thionamide allergy or exogenous thyrotoxicosis. Given concern for long-term relapse, OCAs should be considered a short-term bridge to definitive therapy. OCAs are limited in TMNG and should be second line after glucocorticoids in AIT II. OCAs do not preclude the use of radioactive iodine, which can be performed one week after OCA therapy.

Asunto(s)

RESUMEN

OBJECTIVE: To describe a possible mechanism underlying the partial virilization of a 46, XX infant by a functional maternal adrenocortical carcinoma (ACC). METHODS: We performed immunocytochemical staining of tumor sections for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors. In addition, related reports in the literature are discussed. RESULTS: A previously healthy mother developed a large cortisol- and androgen-producing stage III adrenal tumor that did not interfere with conception or early morphogenesis. The tumor eluded detection until after delivery of a partially virilized 46, XX female infant with ambiguous genitalia. Immunohistochemical staining of tumor sections revealed overexpression of the LH/hCG receptor. Virilization of the genetically female fetus may have resulted from hCG-stimulated steroid secretion by the ACC. CONCLUSION: Because hypercortisolism and hyperandrogenism are associated with menstrual disturbances and spontaneous abortion, pregnancy in patients with functional adrenal tumors is uncommon. Rarely, maternal steroid excess from a functional adrenal tumor has caused 46, XX disordered sex differentiation. This unusual case demonstrates the influence of hCG on the functionality of an ACC and demonstrates the rare phenomenon of virilization of a female infant by a functional maternal adrenal tumor.

Asunto(s)

RESUMEN

OBJECTIVE: The purpose of this study was to analyze the economic outcomes of a clinical program implemented to achieve strict glycemic control with intensive insulin therapy in patients admitted to the intensive care unit (ICU). RESEARCH DESIGN AND METHODS: A difference-in-differences (quasi-experimental) study design was used to examine the associations of an intensive insulin therapy intervention with changes in hospital length of stay (ICU and total), costs (ICU and total), and mortality. Hospital administrative data were obtained for 6,719 adult patients admitted between 2003 and 2005 to one of five intervention or four comparison ICUs in a large academic medical center. Linear regression models with log transformations and appropriate retransformations were used to estimate length of stay (LOS) and costs; logistic regressions were used to estimate mortality. RESULTS: After adjustment for observable patient characteristics and secular time trends, the intervention was consistently associated with lower average glucose levels and a trend toward shorter LOS, lower costs, and lower mortality. However, associations with resource use and outcomes were statistically significant in only ICU LOS, with an average reduction of 1.19 days of ICU care per admission. Other associations, although large in magnitude and in the hypothesized directions, were not estimated with sufficient precision to rule out other net effects. The associations with ICU days and costs were larger in magnitude than total days and costs. CONCLUSIONS: A clinical team focused on hyperglycemia management for ICU patients can be a valuable investment with significant economic benefits for hospitals.

Asunto(s)

RESUMEN

DESIGN: Prevalence of type 2 diabetes and glucose intolerance increase with age. It has been demonstrated that beta cell function declines at about 1% per year in glucose tolerant Caucasians. However, this relationship is not known to exist in other ethnic groups. SUBJECTS AND MEASUREMENTS: We investigated the relationship of age to beta cell function (%B) and insulin sensitivity (%S), estimated by the homeostasis model assessment, in a nationally representative sample of healthy US adults who participated in a cross-sectional study, the third National Health and Nutrition Examination Survey. Only those subjects who had never been told to have diabetes by a physician, with HbA1C < 6% and fasting plasma glucose concentration < 5.56 mmol/l with proper fasting glucose and insulin concentration were included in this analysis (560 non-Hispanic whites, 231 non-Hispanic blacks and 298 Hispanics). RESULTS: Age was positively correlated to HbA1C and fasting glucose concentration, but it was negatively correlated to %B in all three ethnic groups. In contrast, ageing had no influence on %S in all three ethnic groups. Pair-wise comparison showed age had a similar influence among three ethnic groups on fasting glucose concentration, HbA1C and %B, respectively. Multivariate analysis confirmed an independent influence of age on fasting glucose concentration, HbA1C and %B among three ethnic groups. CONCLUSIONS: We observed %B declines at about 1% per year among all three ethnic groups. The age-related rising fasting plasma glucose concentration and HbA1C is most likely a consequence of age-related decline in beta cell function.

Asunto(s)

RESUMEN

PURPOSE: The role of hepatocyte nuclear factor-1alpha (HNF1alpha) in the maturity-onset diabetes of the young 3 (MODY3) is well established. A common polymorphism, I27L that is not linked to MODY3, has been demonstrated to affect beta cell function. To facilitate the identification of subjects with a low beta cell reserve, we developed beta cell indices and validated according to a genetic study. METHODS: Insulin sensitivity index (ISI), 1st phase insulin response (1stIR), and 2nd phase insulin response (2ndIR) were assessed in 60 glucose tolerant subjects using hyperglycemic clamps. Delta1stIR and delta2ndIR were defined as differences between 1stIR (or 2ndIR) and the ISI-adjusted 1stIR (or 2ndIR). The genotypes were determined from genomic DNA. RESULTS: Delta1stIR (P = 0.0130) and delta2ndIR (P = 0.0482) differed among the 3 genotypic groups. Multivariate analysis confirmed the independent influence of the I27L polymorphism on delta1stIR (P = 0.0130) and delta2ndIR (P = 0.0369). Within the LL group, 75% and 63% of the subjects were within the lowest quartile of delta1stIR (P = 0.0011) and delta2ndIR (P = 0.0277), respectively. CONCLUSIONS: With new beta cell indices, we demonstrated the independent impact of the I27L polymorphism on beta cell function. The new beta cell indices will facilitate the identification of glucose tolerant subjects with reduced beta cell reserve.

Asunto(s)

RESUMEN

Plasma glucose and insulin concentrations have been used in genetic studies as quantitative phenotypic traits and also as surrogates for insulin sensitivity and beta-cell function. However, the significance of these traits in relation to insulin sensitivity and beta-cell function was unknown. We examined how insulin sensitivity and beta-cell function affected plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). This is a cross-sectional study enrolling 105 glucose-tolerant subjects (64 females; age, 18 to 40 years; body mass index, 17.58 to 37.57 kg/m(2); waist-to-hip ratio, 0.649 to 1.033 cm/cm). They participated in both OGTTs and hyperglycemic clamps. The relationship between plasma glucose and insulin concentrations and indices of insulin sensitivity and beta-cell function was examined. Univariate analyses showed that insulin sensitivity index (ISI) had some influence on plasma insulin concentrations (r(2) =.2623 to.3814) during the OGTT; however, it had only modest impacts on plasma glucose levels at 60, 90, and 120 minutes (r(2) =.0537 to.1300). Neither first phase (1stIR) nor second phase insulin response (2ndIR) affected plasma glucose concentrations. Multivariate analyses showed an independent impact (all P <.0001) of ISI on plasma glucose concentrations at 60, 90, and 120 minutes and on plasma insulin concentrations at every time point except at 30 minutes. Except for plasma insulin concentration at 30 minutes, of which 24% of the variation can be explained by 1stIR, beta-cell function (either 1stIR or 2ndIR) only had a very modest impact on 30-, 60-, 90- and 120-minute plasma glucose concentrations and on plasma insulin concentration at 60 minutes. In glucose-tolerant subjects, ISI plays an important role in determining postchallenged plasma glucose concentrations at 60, 90, and 120 minutes, as well as plasma insulin concentrations at fasting, 60, 90, and 120 minutes. However, beta-cell function is only reflected in plasma insulin concentration at 30 minutes through 1stIR. Therefore, we conclude that it is essential to measure beta-cell function in vivo if one plans to study the genetic influence of beta-cell dysfunction.

Asunto(s)