Objective: The glucagon stimulation test (GST) like the insulin tolerance test (ITT) stimulates both ACTH and GH secretion. However, there are limited data with modern assays on sensitivity and specificity for GST in comparison to ITT. The aim of this study was to evaluate the diagnostic utility of the GST for GH deficiency (GHD) and adrenal insufficiency (AI) in patients following pituitary surgery. Design and patients: ITT and GST were performed within 7 days in 49 patients at least 3 months after transsphenoidal surgery. Serum GH and cortisol were measured by Immulite 2000 assay (Siemens AG). Receiver-operating characteristic (ROC) analysis was performed to identify the thresholds for GST. Results: In ITT, 18/49 cases were classified as AI. ROC analysis revealed a peak cortisol value O599 nmol/l in GST for adrenal sufficiency with 100% specificity and 32% sensitivity, and a peak cortisol !277 nmol/l with O95% specificity and 72% sensitivity for AI. Of the 49 subjects, 25 (51%) demonstrated levels between these cut-offs and could not be diagnosed by GST alone with sufficient accuracy. Regarding GHD, 21/49 cases were classified as insufficient by ITT. ROC analysis revealed a cut-off of 2.5 ng/ml with 95% sensitivity and 79% specificity. Of the 49 cases, seven (14%) were discordant in terms of defining GHD, with six subjects being treated for GHD according to GST although being sufficient in ITT. Conclusion: In our prospective series of patients with pituitary disease, GST is a potential alternative test for the assessment of GH reserve, but is a poor test for ACTH reserve. Test-specific cut-offs should be applied to avoid misinterpretation.

The insulin tolerance test (ITT) is considered the gold standard for assessment of GH and ACTH reserve in patients with pituitary disease following pituitary surgery and is usually performed after 6-12 weeks. However, abnormal axes may not be completely recovered by then. The aim of this study was to evaluate dynamic testing 3 and 12 months after transsphenoidal pituitary surgery. Design and patients: Serial dynamic testing was performed in 36 patients (13 women, age 18-78) at 3 and 12 months after transsphenoidal surgery. Results: Compared with 3-month results, median GH peak levels during ITT after 12 months increased by 38% (P!0.05). In patients initially classified as GH deficiency (GHD), median GH peak increased after 12 months by 23% (P!0.05). At 3 and 12 months, 36% (13/36) and 47% (17/36) were GH sufficient respectively. Median cortisol peak levels after 12 months increased by 17% (P!0.01) compared with 3-month ITT. In ACTH-insufficient (AI) patients, peak cortisol levels increased significantly by 12% (P!0.05) at 12 months, and in ACTH-sufficient patients, peak cortisol levels increased significantly by 13% (P!0.05). At 12 months, there was recovery from AI in 11% of the patients, and recovery from GHD in 11% of patients. Conclusions: Serial dynamic testing results in a change in classification by ITT results in a relevant proportion of patients. Dynamic testing should be repeated during follow-up.

Background In mechanically ventilated patients with acute respiratory distress syndrome (ARDS), electrical impedance tomography (EIT) provides information on alveolar cycling and overdistension as well as assessment of recruitability at the bedside. We developed a protocol for individualization of positive end-expiratory pressure (PEEP) and tidal volume (VT) utilizing EIT-derived information on recruitability, overdistension and alveolar cycling. The aim of this study was to assess whether the EIT-based protocol allows individualization of ventilator settings without causing lung overdistension, and to evaluate its effects on respiratory system compliance, oxygenation and alveolar cycling. Methods 20 patients with ARDS were included. Initially, patients were ventilated according to the recommendations of the ARDS Network with a VT of 6 ml per kg predicted body weight and PEEP adjusted according to the lower PEEP/FiO2 table. Subsequently, ventilator settings were adjusted according to the EIT-based protocol once every 30 min for a duration of 4 h. To assess global overdistension, we determined whether lung stress and strain remained below 27 mbar and 2.0, respectively. Results Prospective optimization of mechanical ventilation with EIT led to higher PEEP levels (16.5 [14–18] mbar vs. 10 [8–10] mbar before optimization; p = 0.0001) and similar VT (5.7 ± 0.92 ml/kg vs. 5.8 ± 0.47 ml/kg before optimization; p = 0.96). Global lung stress remained below 27 mbar in all patients and global strain below 2.0 in 19 out of 20 patients. Compliance remained similar, while oxygenation was significantly improved and alveolar cycling was reduced after EIT-based optimization. Conclusions Adjustment of PEEP and VT using the EIT-based protocol led to individualization of ventilator settings with improved oxygenation and reduced alveolar cycling without promoting global overdistension. Trial registrationThis study was registered at clinicaltrials.gov (NCT02703012) on March 9, 2016 before including the first patient.

The global inhomogeneity (GI) index is a parameter of ventilation inhomogeneity that can be calculated from images of tidal ventilation distribution obtained by electrical impedance tomography (EIT). It has been suggested that the GI index may be useful for individual adjustment of positive end-expiratory pressure (PEEP) and for guidance of ventilator therapy. The aim of the present work was to assess the influence of tidal volume (VT) on the GI index values. EIT data from 9 patients with acute respiratory distress syndrome ventilated with a low and a high VT of 5   ±   1 (mean  ±  SD) and 9   ±   1 ml kg(-1) predicted body weight at a high and a low level of PEEP (PEEPhigh, PEEPlow) were analyzed. PEEPhigh and PEEPlow were set 2 cmH2O above and 5 cmH2O below the lower inflection point of a quasi-static pressure volume loop, respectively. The lower inflection point was identified at 8.1   ±   1.4 (mean  ±  SD) cmH2O, resulting in a PEEPhigh of 10.1   ±   1.4 and a PEEPlow of 3.1   ±   1.4 cmH2O. At PEEPhigh, we found no significant trend in GI index with low VT when compared to high VT (0.49   ±   0.15 versus 0.44   ±   0.09, p = 0.13). At PEEPlow, we found a significantly higher GI index with low VT compared to high VT (0.66   ±   0.19 versus 0.59   ±   0.17, p = 0.01). When comparing the PEEP levels, we found a significantly lower GI index at PEEPhigh both for high and low VT. We conclude that high VT may lead to a lower GI index, especially at low PEEP settings. This should be taken into account when using the GI index for individual adjustment of ventilator settings.

Parathyroid hormone-related protein (PTHrP) is a major cause of hypercalcemia in malignancy and serum levels are elevated in many patients suffering from this syndrome. In 10 patients with hypercalcemia of malignancy the levels of the midregional fragment of PTHrP in serum were determined by radioimmunoassay over 7 days during a calcium-lowering treatment with a single dose of the bisphosphonate BM 21.0955. PTHrP concentrations remained unchanged 6 days after administration of the drug as compared with pretherapeutic values, thus apparently excluding an effect of either the drug itself or the rapid fall in serum calcium on the release of PTHrP by the tumors or on its clearance from the circulation. In the patients with elevated midregional PTHrP levels (n = 6), the calcium-lowering effect of the drug was significantly less pronounced than in patients with normal PTHrP (n = 4) (mean serum calcium of 2.89 vs. 2.51 mmol/l at day 6), despite similar pretherapeutic concentrations. Of the six patients with elevated PTHrP, five were still hypercalcemic, whereas in the group with normal PTHrP one out of four patients remained hypercalcemic. In conclusion, PTHrP levels in hypercalcemia of malignancy remained unchanged after calcium-lowering therapy with bisphosphonates. High serum PTHrP levels were, however, predictive of a lesser effectiveness of the drug in lowering serum calcium.