Is there a therapeutic role for octreotide in patients with ectopic Cushing's syndrome?

Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS) has a high morbidity and mortality, because of the underlying tumor and the sequelae of severe hypercortisolemia. Therefore, rapid treatment of ectopic CS is mandatory. Scintigraphy shows that up to 80% of ectopic ACTH-producing tumors have somatostatin receptors. While this suggests that somatostatin analogs may reduce ACTH production and treat patients with EAS, the therapeutic role of these agents is still evolving. Here we demonstrate the spectrum of responses to octreotide therapy in 3 patients with EAS. Diagnostic imaging with the 111In-pentetreotide scan did not predict the therapeutic response to octreotide. Two patients with positive somatostatin receptor scintigraphy failed to respond to octreotide, while one with a negative scan reached eucortisolemia on a maintenance dose of 75 microg octreotide twice daily or octreotide LAR 30 mg per month. We conclude that octreotide is not a first line agent to control hypercortisolemia but may be a useful agent when other inhibitors of steroidogenesis fail or parenteral administration is required. Before therapy an octreotide challenge test may predict therapeutic response. Cortisol levels should be monitored regularly on somatostatin analog therapy, because of its unpredictable long-term pharmacodynamic profile.     

The ovine corticotropin-releasing hormone stimulation test and the dexamethasone suppression test in the differential diagnosis of Cushing's syndrome

We gave a standard dexamethasone suppression test and an ovine corticotropin-releasing hormone (CRH) stimulation test to 41 patients with adrenocorticotrophic hormone (ACTH)-dependent hypercortisolism to determine the efficacy of each test in the differential diagnosis of Cushing's syndrome. Twenty-nine of thirty-three patients with Cushing's disease and 0 of 8 patients with ectopic secretion of ACTH responded to the ovine CRH test with increased levels of cortisol. When a cortisol response was judged as positive for Cushing's disease, the CRH test had a diagnostic sensitivity, specificity, and accuracy of 88%, 100%, and 90%, respectively. Twenty-nine patients with Cushing's disease and 1 patient with ectopic secretion of ACTH responded to the dexamethasone suppression test. A combined-test strategy requiring negative results from both tests to exclude a diagnosis of Cushing's disease yielded superior sensitivity (100%) and diagnostic accuracy (98%). Thus, the ovine CRH test works as well as the standard dexamethasone suppression test in discriminating between Cushing's disease and ectopic ACTH secretion. The diagnostic power of each test is enhanced when the two tests are combined.     

Medical Therapy of Cushing's Disease

Surgical excision of an ACTH-producing pituitary tumor is the optimal therapy for Cushing's disease. However, medical therapy may have either a primary or adjunctive role if the patient cannot safely undergo surgery, if surgery fails, or if the tumor recurs. When medication is the only therapy, a major disadvantage is the need for lifelong therapy; in general, recurrence follows discontinuation of treatment. These compounds work through three broad mechanisms of action. Neuromodulatory compounds modulate corticotropin (ACTH) release from a pituitary tumor, steroidogenesis inhibitors reduce cortisol levels by adrenolytic activity and/or direct enzymatic inhibition and glucocorticoid antagonists block cortisol action at its receptor.In general, neuromodulatory compounds (bromocriptine, cyproheptidine, somatostatin and valproic acid) are not very effective agents for Cushing's disease. Treatment with a glucocorticoid antagonist and radiation therapy has been reported on a single patient only. Steroidogenesis inhibitors, including mitotane, metyrapone, ketoconazole, and aminoglutethimide, are the agents of choice for medical therapy of Cushing's disease. In general, ketoconazole is the best tolerated of these agents and is effective as monotherapy in about 70% of patients. Mitotane and metyrapone may be effective as single agents, while aminoglutethimide generally must be given in combination. The intravenously-administered etomidate may used when patients cannot take medications by mouth.     

Diagnostic accuracy of intra-abdominal fluid collection characterization in the era of multidetector computed tomography

The purpose of this study was to test the hypothesis that with improved technology, the presence of abscess in a postoperative fluid collection may be prospectively made. This is an Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective review of computed tomography (CT)-guided intra-abdominal fluid collection drainages. The diagnostic CT scans of 95 consecutive patients performed on 16- and 64-multidetector CT (MDCT) were reviewed by four readers with varying abdominal imaging expertise. Readers were asked to determine fluid content, to document whether infection was present, and to rate reader confidence for infection. A fifth radiologist reviewed the collections for imaging characteristics. The gold standard for presence of infection was microbiological Gram stain and culture. The logistic regression model showed that both fluid collections containing gas or high attenuation fluid (average CT density 20 or greater Hounsfield units) are significant predictors of infection (P = 0.001). The average sensitivity over the four readers for determining presence of infection was 83.4 per cent and specificity was 39.3 per cent. Even in the era of MDCT, the ability to predict whether or not a fluid collection is infected or not, based on imaging findings alone, is limited. Presence of gas is a strong indicator of infection, but no imaging finding is characteristic of a sterile fluid collection.     

Psychosocial aspects of child and adolescent obesity

In addition to counselling families about regular physical activity and healthy nutrition, clinicians need to identify and help them to address the psychosocial factors that may be contributing to their child’s or adolescent’s obesity. Affected individuals may suffer from depression, low self-esteem, bullying, and weight bias, experiences that can make achieving desired health outcomes more difficult. Clinicians should try to identify these underlying stressors and ensure that appropriate counselling is implemented.     

Nighttime salivary cortisol: a useful test for the diagnosis of Cushing's syndrome

Clinical features such as weight gain, depression, hypertension, and menstrual irregularities, although common in the general population, may raise the possibility of Cushing's syndrome. Up to 30% of urine cortisol and dexamethasone suppression screening tests may return an incorrect result, suggesting that better tests are needed. This study evaluated the utility of nighttime salivary cortisol measurement as a screening test for Cushing's syndrome. We evaluated 139 inpatients and 4 outpatients with possible Cushing's syndrome, 16 inpatients and 7 outpatients with other nonadrenal disorders, and 34 healthy outpatients. Using cut points that excluded all subjects without Cushing's syndrome, we compared the sensitivity for the detection of Cushing's syndrome of nighttime salivary cortisol levels (2330 and 2400 h for inpatients and bedtime for outpatients), simultaneous inpatient serum cortisol levels, and urine glucocorticoid excretion. An assay- specific inpatient 2400-h salivary cortisol or an outpatient bedtime salivary cortisol greater than 550 ng/dl (15.2 nmol/liter) identified 93% of patients with Cushing's syndrome (confidence interval, 89-98%) and excluded all individuals without the disorder. Salivary cortisol measurements worked as well as plasma measurements and better than urine glucocorticoid excretion. We concluded that bedtime salivary cortisol measurement is a practical and accurate screening test for the diagnosis of Cushing's syndrome.     

The effects of moderate exercise training on immune response

The relationship between moderate exercise training (ET) (five 45-min sessions per week, brisk walking at 60 heart rate reserve for 15 wk) and changes in immune system variables and function was investigated in a group of 36 sedentary, mildly obese women. The study was conducted using a two (exercise (EX) and nonexercise (NEX) groups) by three (baseline, 6 wk, and 15 wk testing sessions) factorial design, with data analyzed using repeated measures ANOVA. The pattern of change over time between groups for number of peripheral blood lymphocytes (total), T cells (CD5), B cells (CD20), and serum IgG, IgA, and IgM levels was significantly different. This was not the case for spontaneous blastogenesis or number of T helper/inducer cells (CD4) or T cytotoxic/suppressor cells (CD8). Within-EX-group changes were characterized by significant decreases in percentage and number of total lymphocytes, and in T cell number after 6 wk, and significant increases in each of the serum immunoglobulins after both 6 and 15 wk of training. B cell number increased significantly in NEX subjects relative to baseline values at both 6 and 15 wk, with no significant changes experienced in EX subjects. In summary, these data suggest that moderate ET is not associated with an improvement in lymphocyte function but is associated with a 20% increase in serum immunoglobulins and several small changes in circulating numbers of immune system variables, highlighted by significant decreases in circulating numbers of lymphocytes, particularly the T cell subpopulation. These changes were especially apparent after 6 wk of training, with some attenuation by 15 wk.     

Vascular reactivity during haemodialysis and isolated ultrafiltration: thermal influences

BACKGROUND.: The present study was performed to assess the role of the extracorporealblood temperature in the disparate cardiovascular response betweenisolated ultrafiltration and combined ultrafiltration-haemodialysis. METHODS.: In twelve stable dialysis patients (21–77 years), bloodpressure and heart rate (Finapres) as well as forearm vascularresistance and venous tone (strain-gauge plethysmography) weremeasured during 1-h isolated ultrafiltration and 1-h combinedultrafiltration-haemodialysis (bicarbonate, sodium 141 mmol/l)at a fixed ultrafiltration rate of 0.91 l/h. The sequence ofboth treatment modalities was randomly defined within each patient.Serving as his or her own control, each patient was studiedat two different dialysate temperatures: 37.5 and 35.0°C. RESULTS.: At a dialysate temperature of 35.0°C extra-corporeal bloodcooling during combined ultrafiltration-haemodialysis was comparableto isolated ultrafiltration. The cardiovascular response inisolated ultrafiltration was characterized by a significantincrease in both forearm vascular resistance and venous tone,while heart rate even decreased. As a result, blood pressureremained unchanged or even increased. In contrast, during combinedultrafiltration-haemodialysis at a dialysate temperature of37.5°C the increase in forearm vascular resistance was onlysmall and insignificant, while venous tone decreased significantly.Heart rate tended to increase. Combined ultrafiltration-haemodialysisat a dialysate temperature of 35.0°C was also associatedwith a small increase in forearm vascular resistance. However,venous tone remained stable while heart rate decreased. At bothdialysate temperatures, blood pressure was well maintained. CONCLUSIONS.: We conclude that differences in cardiovascular reactivity betweenisolated ultrafiltration and combined ultrafiltration-haemodialysisare only partially explained by differences in the extracorporealblood temperature. In addition, especially venous reactivityis improved by lowering the dialysate temperature.