Utility of 30 and 60 minute cortisol samples after high-dose synthetic ACTH-1-24 injection in the diagnosis of adrenal insufficiency

BACKGROUND: In clinical practise the high dose ACTH stimulation test (HDT) is frequently used in the assessment of adrenal insufficiency (AI). However, there is uncertainty regarding optimal time-points and number of blood samplings. The present study compared the utility of a single cortisol value taken either 30 or 60 minutes after ACTH stimulation with the traditional interpretation of the HDT. METHODS: Retrospective analysis of 73 HDT performed at a single tertiary endocrine centre. Serum cortisol was measured at baseline, 30 and 60 minutes after intravenous administration of 250 µg synthetic ACTH1-24. Adrenal insufficiency (AI) was defined as a stimulated cortisol level <550 nmol/l. RESULTS: There were twenty patients (27.4%) who showed an insufficient rise in serum cortisol using traditional HDT criteria and were diagnosed to suffer from AI. There were ten individuals who showed insufficient cortisol values after 30 minutes, rising to sufficient levels at 60 minutes. All patients revealing an insufficient cortisol response result after 60 minutes also had an insufficient result after 30 minutes. The cortisol value taken after 30 minutes did not add incremental diagnostic value in any of the cases under investigation compared with the 60 minutes' sample. CONCLUSIONS: Based on the findings of the present analysis the utility of a cortisol measurement 30 minutes after high dose ACTH injection was low and did not add incremental diagnostic value to a single measurement after 60 minutes.

Prospective analysis of adrenal function in patients with acute exacerbations of COPD: the Reduction in the Use of Corticosteroids in Exacerbated COPD (REDUCE) trial

OBJECTIVE To analyze prospectively the hypothalamic-pituitary-adrenal (HPA) axis and clinical outcome in patients treated with prednisone for exacerbated chronic obstructive pulmonary disease (COPD). DESIGN Prospective observational study. SUBJECTS AND METHODS Patients presenting to the emergency department were randomized to receive 40 mg prednisone daily for 5 or 14 days in a placebo-controlled manner. The HPA axis was longitudinally assessed with the 1 μg corticotropin test and a clinical hypocortisolism score at baseline, on day 6 before blinded treatment, at hospital discharge, and for up to 180 days of follow-up. Prednisone was stopped abruptly, irrespective of the test results. Patients discharged with pathological test results received instructions about emergency hydrocortisone treatment. RESULTS A total of 311 patients were included in the analysis. Mean basal and stimulated serum total cortisol levels were highest on admission (496±398 and 816±413 nmol/l respectively) and lowest on day 6 (235±174 and 453±178 nmol/l respectively). Pathological stimulation tests were found in 63, 38, 9, 3, and 2% of patients on day 6, at discharge, and on days 30, 90, and 180 respectively, without significant difference between treatment groups. Clinical indicators of hypocortisolism did not correlate with stimulation test results, but cortisol levels were inversely associated with re-exacerbation risk. There were no hospitalizations or deaths as a result of adrenal crisis. CONCLUSION Dynamic changes in the HPA axis occur during and after the treatment of acute exacerbations of COPD. In hypocortisolemic patients who were provided with instructions about stress prophylaxis, the abrupt termination of prednisone appeared safe.

Regulation of human (adrenal) androgen biosynthesis-New insights from novel throughput technology studies

Androgens are precursors for sex steroids and are predominantly produced in the human gonads and the adrenal cortex. They are important for intrauterine and postnatal sexual development and human reproduction. Although human androgen biosynthesis has been extensively studied in the past, exact mechanisms underlying the regulation of androgen production in health and disease remain vague. Here, the knowledge on human androgen biosynthesis and regulation is reviewed with a special focus on human adrenal androgen production and the hyperandrogenic disorder of polycystic ovary syndrome (PCOS). Since human androgen regulation is highly specific without a good animal model, most studies are performed on patients harboring inborn errors of androgen biosynthesis, on human biomaterials and human (tumor) cell models. In the past, most studies used a candidate gene approach while newer studies use high throughput technologies to identify novel regulators of androgen biosynthesis. Using genome wide association studies on cohorts of patients, novel PCOS candidate genes have been recently described. Variant 2 of the DENND1A gene was found overexpressed in PCOS theca cells and confirmed to enhance androgen production. Transcriptome profiling of dissected adrenal zones established a role for BMP4 in androgen synthesis. Similarly, transcriptome analysis of human adrenal NCI-H295 cells identified novel regulators of androgen production. Kinase p38α (MAPK14) was found to phosphorylate CYP17 for enhanced 17,20 lyase activity and RARB and ANGPTL1 were detected in novel networks regulating androgens. The discovery of novel players for androgen biosynthesis is of clinical significance as it provides targets for diagnostic and therapeutic use.

Use of Otolith Strontium:Calcium Ratios for Hindcasting Larval Cod Gadus Morhua Distributions Relative to Water Masses on Georges Bank

The concentration ratios of strontium to calcium in laboratory-reared larval cod otoliths are shown to be related to the water temperature (T) at the time of otolith precipitation. This relationship is curvilinear, and is best described by a simple exponential equation of the form (Sr/Ca x 1000 = a exp(-T/b). We show that when Sr/Ca elemental analyses are related to the daily growth increments in the larval otoliths, relative temperature histories of individual field-caught larvae can be reconstructed from the egg stage to the time of capture. We present preliminary examples of how such reconstructed temperature histories of Atlantic cod Gadus morhua larvae, collected on Georges Bank during April and May 1993, may be interpreted in relation to the broad-scale larval distributions and the hydrography of the Bank.

(Table 2) Characteristics of influence of cyclonic and anticyclonic activity of water masses on hydrophysical, hydrochemical, and hydrobiological parameters in the southern part of the Black Sea in September 1996

Characteristics of the spatial structure of vertical synoptic currents were calculated from data of the density field surveys in order to estimate their influence on distribution of chlorophyll a concentration. Comparisons of chlorophyll concentration and vertical currents were implemented for two multidisciplinary surveys in the Black Sea carried out in summer, 1991 and in winter, 1994. The results showed qualitative and quantitative indications of coincidence of characteristics cited and, in particular, significant positive values of the correlation coefficient (0.65 for the summer survey and 0.83 for the winter one).

Gill tissue masses and oxygen consumption of Gobionotothen gibberifrons, Notothenia coriiceps and Zoarces viviparus

Mechanisms responsive to hypercapnia (elevated CO2 concentrations) and shaping branchial energy turnover were investigated in isolated perfused gills of two Antarctic Notothenioids (Gobionotothen gibberifrons, Notothenia coriiceps). Branchial oxygen consumption was measured under normo- versus hypercapnic conditions (10,000 ppm CO2) at high extracellular pH values. The fractional costs of ion regulation, protein and RNA synthesis in the energy budgets were determined using specific inhibitors. Overall gill energy turnover was maintained under pH compensated hypercapnia in both Antarctic species as well as in a temperate zoarcid (Zoarces viviparus). However, fractional energy consumption by the examined processes rose drastically in G. gibberifrons (100-180%), and to a lesser extent in N. coriiceps gills (7-56%). In conclusion, high CO2 concentrations under conditions of compensated acidosis induce cost increments in epithelial processes, however, at maintained overall rates of branchial energy turnover.

Properties of water masses, taxa abundance, and isotopic ratios of samples obtained around Svalbard archipelago

The feeding strategies of Calanus hyperboreus, C. glacialis, and C. finmarchicus were investigated in the high-Arctic Svalbard region (77-81 °N) in May, August, and December, including seasons with algal blooms, late- to post-bloom situations, and unproductive winter periods. Stable isotope and fatty acid trophic marker (FATM) techniques were employed together to assess trophic level (TL), carbon sources (phytoplankton vs. ice algae), and diet of the three Calanus species. In addition, population development, distribution, and nutritional state (i.e. storage lipids) were examined to estimate their population status at the time of sampling. In May and August, the vertical distribution of the three Calanus species usually coincided with the maximum algal biomass. Their stable isotope and fatty acid (FA) composition indicated that they all were essentially herbivores in May, when the algal biomass was highest. Their FA composition, however, revealed different food preferences. C. hyperboreus had high proportions of 18:4n3, suggesting that it fed mainly on Phaeocystis, whereas C. glacialis and C. finmarchicus had high proportions of 16:4n1, 16:1n7, and 20:5n3, suggesting diatoms as their major food source. Carbon sources (i.e. phytoplankton vs. ice algae) were not possible to determine solely from FATM techniques since ice-diatoms and pelagic-diatoms were characterised by the same FA. However, the enriched d13C values of C. glacialis and C. finmarchicus in May indicated that they fed both on pelagic- and ice-diatoms. Patterns in absolute FA and fatty alcohol composition revealed that diatoms were the most important food for C. hyperboreus and C. glacialis, followed by Phaeocystis, whereas diatoms, Phaeocystis and other small autotrophic flagellates were equally important food for C. finmarchicus. During periods of lower algal biomass, only C. glacialis exhibited evidence of significant dietary switch, with a TL indicative of omnivory (mean TL=2.4). Large spatial variability was observed in population development, distribution, and lipid store sizes in August. At the northernmost station at the southern margin of the Arctic Ocean, the three Calanus species had similarly low lipid stores as they had in May, suggesting that they ascended later in the year. In December, relatively lipid-rich specimens had TL similar to those during the peak productive season (TL~2.0), suggesting that they were hibernating and not feeding on the available refractory material available at that time of the year. In contrast, lipid-poor specimens in December had substantially high TL (TL=2.5), suggesting that they were active and possibly were feeding.

Phytoplankton production, photosynthetic (P vs E) parameters, and particulate organic carbon and nitrogen within distinct water masses of eastern Australian coastal and shelf waters between 29 °S and 36 °S during spring 2010

The present dataset is part of an interdisciplinary project carried out on board the RV Southern Surveyor off New South Wales (Australia) from the 15th to the 31st October 2010. The main objective of the research voyage was to evaluate how the East Australian Current (EAC) affects the optical, chemical, physical, and biological water properties of the continental shelf and slope off the NSW coast.