This meta-analysis showed that hyperprolactinemia will recur after dopamine agonist withdrawal in a considerable proportion of patients. The probability of treatment success was highest when cabergoline was used for at least 2 yr.
The main purpose was to assess the incidence and late outcome of Cushing's syndrome, particularly in Cushing's disease. Information for all patients diagnosed with Cushing's syndrome during an 11-yr period in Denmark was retrieved. The incidence was 1.2-1.7/million.yr (Cushing's disease), 0.6/million.yr (adrenal adenoma) and 0.2/million.yr (adrenal carcinoma). Other types of Cushing's syndrome were rare. In 139 patients with nonmalignant disease, 11.1% had died during follow-up (median, 8.1 yr; range, 3.1-14.0), yielding a standard mortality ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34-5.33]. The SMR was partly attributable to an increased mortality within the first year after diagnosis. Eight patients died before treatment could be undertaken. The prognosis in patients with malignant disease was very poor. Patients in whom more than 5 yr had elapsed since initial surgery were studied separately, including a questionnaire on their perceived quality of health. In 45 patients with Cushing's disease who had been cured through transsphenoidal neurosurgery, only 1 had died (SMR, 0.31; CI, 0.01-1.72) compared with 6 of 20 patients with persistent hypercortisolism after initial neurosurgery (SMR, 5.06; CI, 1.86-11.0). In patients with adrenal adenoma, SMR was 3.95 (CI, 0.81-11.5). The perceived quality of health was significantly impaired only in patients with Cushing's disease and appeared independent of disease control or presence of hypopituitarism. It is concluded that 1) Cushing's syndrome is rare and is associated with increased mortality, in patients with no concurrent malignancy also; 2) the excess mortality was mainly observed during the first year of disease; and 3) the impaired quality of health in long-term survivors of Cushing's disease is not fully explained.
Preoperative use of SSRIs was not associated with any substantially increased requirement for allogeneic red blood cell transfusion among patients undergoing CABG. The main strengths of this study are its relatively large size, the use of prospectively collected data obtained from population-based databases with complete follow-up, and the ability to examine specific types of antidepressants. The limitations include a lack of detailed clinical data regarding other factors that may influence transfusion requirements.
Pelvic insufficiency fractures (PIF) is a known but under-acknowledged late effect of pelvic radiotherapy. In rectal cancer, studies describing incidence of PIF and relation to dose volume relationships are lacking. The aim of this study was (i) to analyse dose volume histograms (DVH) from pelvic bones in patients with and without PIF, and (ii) to determine bone sparing capacity of 2 and 3 arc volumetric arc therapy (VMAT), intensity modulated radiotherapy (IMRT) and proton beam therapy (PBT), in rectal cancer patients treated with chemoradiotherapy (CRT). Material and methods: Patients treated with CRT for primary rectal cancer underwent a 3-year pelvic MRI for identification of PIFs. Bone structures were retrospectively delineated, and DVHs were recalculated. Comparative planning was done with 2 (original) and 3 arc VMAT, fixed field IMRT and PBT plans. Results: 27 patients (18 men, mean age 64 years) were included and PIFs were identified in 9 (33%), most (n = 6) had multiple fracture sites. In general, patients with PIFs received higher doses to pelvic bones, and V30 Gy to the sacroiliac joint was non-significantly higher in patients with PIF 68.5% (60.1-69.3 IQR) vs. 56% (54.1-66.6 IQR), p = 0.064. Comparative planning showed that especially 3 arc VMAT and proton beam therapy could be optimized for bone. Conclusions: Patients, treated with VMAT based CRT for rectal cancer, have high rates of PIFs after 3 years. Patients with PIFs tended to have received higher doses to sacroiliac joints. Comparative planning demonstrated most pronounced bone sparing capacity of 3 arc VMAT and with PBT having the potential to further lower doses. These results should be validated in larger and preferably prospective cohorts.
The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse.
Objective: To enhance the precision of the risk estimate for breast cancer in hyperprolactinemia patients by collecting more data and pooling our results with available data from former studies in a meta-analysis. Design: Population-based cohort study and meta-analysis of the literature. Methods: Using nationwide registries, we identified all patients with a first-time diagnosis of hyperprolactinemia during 1994-2012 including those with a new breast cancer diagnoses after the start of follow-up. We calculated standardised incidence ratios (SIRs) as a measure of relative risk (RR) using national cancer incidence rates. We performed a meta-analysis, combining data from our study with data in the existing literature. Results: We identified 2457 patients with hyperprolactinemia and 20 breast cancer cases during 19 411 person-years of follow-up, yielding a SIR of 0.99 (95% CI 0.60-1.52). Data from two additional cohort studies were retrieved and analyzed. When the three risk estimates were pooled, the combined RR was 1.04 (95% CI 0.75-1.43). Conclusions: We found no increased risk of breast cancer among patients with hyperprolactinemia.
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