To determine whether petrosal sinus sampling is useful to distinguish patients with mild or intermittent Cushing's disease from normal subjects and individuals with pseudo-Cushing states, we performed bilateral inferior petrosal sinus sampling for ACTH before and after the administration of CRH in 7 eucortisolemic volunteers, 8 hypercortisolemic patients with pseudo-Cushing states, and 40 patients with ACTH-dependent Cushing's disease whose urinary free cortisol excretion was within the range found in patients with, pseudo-Cushing states (< 1000 nmol/day; < 360 micrograms/day). The ACTH level, the ratio of the inferior petrosal sinus ACTH to the peripheral venous ACTH concentration (the IPS:P ratio), and the greater ratio of right to left or left to right petrosal sinuses (the R:L ratio) were compared in patients with and without Cushing's disease. Maximal petrosal ACTH values were significantly elevated in patients with Cushing's disease compared to patients with pseudo-Cushing states before CRH administration (P < 0.001), but not after CRH. Maximal petrosal plasma ACTH values after the administration of CRH as high as 808 pmol/L (3670 pg/mL) and 469 pmol/L (2130 pg/mL) were found in patients with pseudo-Cushing states and in normal volunteers, respectively, whereas maximal petrosal ACTH levels as low as 10 pmol/L (46 pg/mL) were observed in patients with surgically proven Cushing's disease. Maximal and minimal IPS:P ratios were significantly greater in patients with Cushing's disease than in subjects without Cushing's disease before, but not after, CRH treatment. R:L ratios did not differ among groups either before or after CRH. All of the subjects without Cushing's disease showed large R:L gradients, consistent with the notion of one dominant petrosal sinus containing a greater percentage of pituitary effluent. The ACTH concentrations, IPS:P ratios, and R:L ratios exhibited great overlap between those with and without Cushing's disease, which resulted in a diagnostic accuracy of 81% at best for the diagnosis of Cushing's disease. We conclude that petrosal sinus sampling is of limited usefulness in distinguishing either normal individuals or patients with pseudo-Cushing states from those with mild Cushing's disease. This limited usefulness must be recognized when interpreting the results of petrosal sinus sampling in patients with mild or intermittent hypercortisolism who may have a pseudo-Cushing state. Because of these limitations, petrosal sinus sampling should be reserved for patients with clear clinical and biochemical evidence of Cushing's syndrome.
Buried steel pipelines transporting oil and oil products play a vital role in the energy supply chain.Pipelines extend to long distances and thus intercepting tectonic faults, when a seismic area is crossed, is often inevitable and may heavily threat the pipeline integrity.Earthquakes and the associated fault displacements are naturally random events and therefore the imposed large ground displacements on the pipeline have to be considered through a probabilistic perspective.In the present study, a comprehensive seismic risk analysis of buried pipelinefault crossing is presented, consisting of two steps.The first step is the probabilistic assessment of the fault displacement accounting also for the pertinent uncertainties.The second step is the pipeline structural analysis.The transition from the seismological data to the structural analysis is realized through the fault displacement components as the selected vector intensity measure.The outcome of the proposed methodology is the strain hazard curves for both tensile and compressive longitudinal strains.The resulting strain capacities are compared to strain demands from structural codes in order to assess the potential of pipeline failure due to local buckling or tensile fracture.Furthermore, uncertainty and disaggregation results from the fault displacement hazard analysis are presented for the selection of the appropriate deterministic design scenario and the evaluation of the fault displacement hazard parameters.Lastly, the proposed process is a reliable estimation tool for seismic risk assessment of pipelinefault crossing and a decision making tool for route selection and application of preventive measures against the consequences of faulting on pipelines.
This chapter helps the analyst decide how to model the structural system as a whole. It aims for modeling accuracy that is sufficient for design and addresses evaluation of diaphragm stiffness. The chapter discusses modeling details such as the choice of elements to use for modeling structural components and the specification of element properties. It should be noted that choices in discretization of the structure and modeling of structural components affect computed deformations, and thus the acceptability of a given design is a function not only of the modeling choices, but also of the modeling basis assumed when the acceptance criteria values were established. Modeling of diaphragm flexibility requires use of a three-dimensional model. Unrealistically large damping forces can arise when conventional damping models are used in models of structures undergoing significant softening during nonlinear response.
Hyperprolactinemic patients may have increases in plasma dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS). We examined the effect of lowering serum PRL with bromocriptine or pituitary surgery on the serum concentrations of adrenal androgens and on the production rate (PR) and MCR of DHAS in eight hyperprolactinemic women (HP). We also examined the effect of bromocriptine therapy on adrenal androgens in five normal men. Serum DHAS was elevated in HP compared to normal women (mean ± SEM, 254 ± 28 vs. 182 ± 13 µg/dl; P < 0.04). Serum DHA and androstenedione (Δ4) in HP were not significantly different from normal. Serum PRL fell from 160 ± 16 to 37 ± 9 ng/ml during or after treatment. Mean 24-h serum DHAS fell from 198 ± 30 to 106 ± 17 µg/dl (P < 0.001) with treatment, without a change in the mean 24-h serum cortisol concentration (6.2 ± 0.4 vs. 6.6 ± 0.4 Mg/dl). Thus, the DHAS to cortisol (DHAS/F) ratio fell significantly (32± 5 to 17 ± 4; P < 0.001). This was also true of the DHAS/F ratio during ACTH stimulation (8 ± l t o 6 ± l ; P < 0.02). Similar changes were found in basal and ACTH-stimulated DHA/F ratios, whereas the basal and ACTH-stimulated A4/F ratios did not change significantly with treatment. Treatment lowered the PR of DHAS from 27 ŷ 5 to 17 ± 3 mg/24 h (P < 0.03) and increased the DHAS MCR from 16 ± 2 to 21 ± 3 liters/24 h (P < 0.01). Bromocriptine treatment of normal men lowered serum PRL from 15 ± 2 to less than 2.5 ng/ml. There were no significant changes in the basal and ACTH-stimulated serum DHAS/F, DHA/F, or Δ4F ratios or DHAS PR and MCR during bromocriptine therapy. The failure of bromocriptine to significantly alter these steroids in normal men suggests that bromocriptine was not directly responsible for the changes in HP treated with this drug. A mechanism for the increased PR of DHAS in HP was sought by examining the serum concentrations of the steroid biosynthetic intermediates relevant to DHAS production. Lowering serum PRL was associated with a decrease in basal and ACTH-stimulated 17-hydroxypregnenolone/17-hydroxyprogesterone and DHA/Δ4 ratios, suggesting an increase in 3β-hydroxysteroid dehydrogenase/Δ4,5-isomerase activity. However, increased gonadal secretion of the Δ4-steroids may have occurred with the fall in serum PRL. With treatment, both basal and ACTH-stimulated 17-hydroxypregnenolone/DHA and 17-hydroxyprogesterone/Δ4 ratios increased, suggesting a fall in 17,20- desmolase activity. The basal DHA/DHAS ratio increased after treatment without a change in the ACTH-stimulated ratio, suggesting a fall in peripheral sulfokinase activity. We conclude that hyperprolactinemia is associated with an elevation of serum DHAS, which primarily reflects an increased DHAS PR. The mechanism of the increased DHAS PR may include increased 17,20-desmolase activity, increased peripheral sulfokinase activity, and, possibly, decreased 3β-hydroxysteroid dehydrogenase/Δ4,5-isomerase activity.
Ovine and human corticotropin-releasing factors (CRF) have similar potencies in causing adrenocorticotropic hormone (ACTH) and cortisol secretion in normal humans. Using long-acting ovine CRF (1 µg/kg body weight as an intravenous bolus), we tested patients with Cushing's syndrome, adrenal insufficiency, and psychiatric conditions with mild hypercortisolism. Over 95% of hypercortisolemic patients with a pituitary adenoma responded with increases in plasma ACTH and cortisol concentrations; patients with the ectopic ACTH syndrome had no ACTH or cortisol responses; patients with ACTH-independent hypercortisolism of adrenal origin had low or undetectable plasma ACTH concentrations before and after CRF without any cortisol response. The differences in responses of patients with adrenal insufficiency of primary, pituitary, or suprapituitary type likewise suggest value of the CFR test in their differential diagnosis. The responses in the psychiatric patients should permit differentiation between Cushing's syndrome and hypercortisolism of psychiatric origin.
