Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure.

Maternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Importantly, a clinically relevant connection exists between inflammation and metabolic stress that can result in aberrant cytokine signaling and autoimmunity. In this study we examined the potential for maternal autoantibodies (aAbs) to disrupt metabolic signaling and induce neuroanatomical changes in the brains of exposed offspring. To accomplish this, we developed a model of maternal aAb exposure in rats based on the clinical phenomenon of maternal autoantibody-related ASD (MAR-ASD). Following confirmation of aAb production in rat dams and antigen-specific immunoglobulin G (IgG) transfer to offspring, we assessed offspring behavior and brain structure longitudinally. MAR-ASD rat offspring displayed a reduction in pup ultrasonic vocalizations and a pronounced deficit in social play behavior when allowed to freely interact with a novel partner. Additionally, longitudinal in vivo structural magnetic resonance imaging (sMRI) at postnatal day 30 (PND30) and PND70, conducted in a separate cohort of animals, revealed sex-specific differences in total and regional brain volume. Treatment-specific effects by region appeared to converge on midbrain and cerebellar structures in MAR-ASD offspring. Simultaneously, in vivo 1H magnetic resonance spectroscopy (1H-MRS) data were collected to examine brain metabolite levels in the medial prefrontal cortex. Results showed that MAR-ASD offspring displayed decreased levels of choline-containing compounds and glutathione, accompanied by increased taurine compared to control animals. Overall, we found that rats exposed to MAR-ASD aAbs present with alterations in behavior, brain structure, and neurometabolites; reminiscent of findings observed in clinical ASD.

[11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial.

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma is a common cause of hypertension. This can be cured, or greatly improved, by adrenal surgery. However, the invasive nature of the standard pre-surgical investigation contributes to fewer than 1% of patients with PA being offered the chance of a cure. The primary objective of our prospective study of 143 patients with PA ( NCT02945904 ) was to compare the accuracy of a non-invasive test, [11C]metomidate positron emission tomography computed tomography (MTO) scanning, with adrenal vein sampling (AVS) in predicting the biochemical remission of PA and the resolution of hypertension after surgery. A total of 128 patients reached 6- to 9-month follow-up, with 78 (61%) treated surgically and 50 (39%) managed medically. Of the 78 patients receiving surgery, 77 achieved one or more PA surgical outcome criterion for success. The accuracies of MTO at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7 and 65.4%. For AVS, the accuracies were 63.6 and 61.5%. MTO was not significantly superior, but the differences of 9.1% (95% confidence interval = -6.5 to 24.1%) and 3.8% (95% confidence interval = -11.9 to 9.4) lay within the pre-specified -17% margin for non-inferiority (P = 0.00055 and P = 0.0077, respectively). Of 24 serious adverse events, none was considered related to either investigation and 22 were fully resolved. MTO enables non-invasive diagnosis of unilateral PA.

Performance evaluation of scoring systems for predicting post-operative hypertension cure in primary aldosteronism.

OBJECTIVE: Hypertension cure following adrenalectomy in unilateral primary aldosteronism is not guaranteed. Its likelihood is associated with pre-operative parameters, which have been variably combined in six different predictive scoring systems. The relative performance of these systems is currently unknown. The objective of this work was to identify the best performing scoring system for predicting hypertension cure following adrenalectomy for primary aldosteronism. DESIGN: Retrospective analysis in a single tertiary referral centre. PATIENTS: Eighty-seven adult patients with unilateral primary aldosteronism who had undergone adrenalectomy between 2004 and 2018 for whom complete data sets were available to calculate all scoring systems. MEASUREMENTS: Prediction of hypertension cure by each of the six scoring systems. RESULTS: Hypertension cure was achieved in 36/87 (41.4%) patients within the first post-operative year, which fell to 18/71 (25.4%) patients at final follow-up (median 53 months, P = .002). Analysis of receiver operating characteristic area under the curves for the different scoring systems identified a difference in performance at early, but not late, follow-up. For all systems, the area under the curve was lower at early compared with late follow-up and compared to performance in the cohorts in which they were originally defined. CONCLUSIONS: No single scoring system performed significantly better than all others when applied in our cohort, although two did display particular advantages. It remains to be determined how best such scoring systems can be incorporated into the routine clinical care of patients with PA.

COVID-19 and pneumothorax: a multicentre retrospective case series.

INTRODUCTION: Pneumothorax and pneumomediastinum have both been noted to complicate cases of coronavirus disease 2019 (COVID-19) requiring hospital admission. We report the largest case series yet described of patients with both these pathologies (including nonventilated patients). METHODS: Cases were collected retrospectively from UK hospitals with inclusion criteria limited to a diagnosis of COVID-19 and the presence of either pneumothorax or pneumomediastinum. Patients included in the study presented between March and June 2020. Details obtained from the medical record included demographics, radiology, laboratory investigations, clinical management and survival. RESULTS: 71 patients from 16 centres were included in the study, of whom 60 had pneumothoraces (six with pneumomediastinum in addition) and 11 had pneumomediastinum alone. Two of these patients had two distinct episodes of pneumothorax, occurring bilaterally in sequential fashion, bringing the total number of pneumothoraces included to 62. Clinical scenarios included patients who had presented to hospital with pneumothorax, patients who had developed pneumothorax or pneumomediastinum during their inpatient admission with COVID-19 and patients who developed their complication while intubated and ventilated, either with or without concurrent extracorporeal membrane oxygenation. Survival at 28 days was not significantly different following pneumothorax (63.1±6.5%) or isolated pneumomediastinum (53.0±18.7%; p=0.854). The incidence of pneumothorax was higher in males. 28-day survival was not different between the sexes (males 62.5±7.7% versus females 68.4±10.7%; p=0.619). Patients aged ≥70 years had a significantly lower 28-day survival than younger individuals (≥70 years 41.7±13.5% survival versus <70 years 70.9±6.8% survival; p=0.018 log-rank). CONCLUSION: These cases suggest that pneumothorax is a complication of COVID-19. Pneumothorax does not seem to be an independent marker of poor prognosis and we encourage continuation of active treatment where clinically possible.

Low-grade Cortisol Cosecretion Has Limited Impact on ACTH-stimulated AVS Parameters in Primary Aldosteronism.

CONTEXT: In primary aldosteronism, cosecretion of cortisol may alter cortisol-derived adrenal venous sampling indices. OBJECTIVE: To identify whether cortisol cosecretion in primary aldosteronism alters adrenal venous sampling parameters and interpretation. DESIGN: Retrospective case-control study. SETTING: A tertiary referral center. PATIENTS: 144 adult patients with primary aldosteronism who had undergone both adrenocorticotropic hormone-stimulated adrenal venous sampling and dexamethasone suppression testing between 2004 and 2018. MAIN OUTCOME MEASURES: Adrenal venous sampling indices including adrenal vein aldosterone/cortisol ratios and the selectivity, lateralization, and contralateral suppression indices. RESULTS: 21 (14.6%) patients had evidence of cortisol cosecretion (defined as a failure to suppress cortisol to ≤50 nmol/L post dexamethasone). Patients with evidence of cortisol cosecretion had a higher inferior vena cava cortisol concentration (P = .01) than those without. No difference was observed between the groups in terms of selectivity index, lateralization index, lateralization of aldosterone excess, or adrenal vein cannulation rate. CONCLUSIONS: Cortisol cosecretion alters some parameters in adrenocorticotrophic hormone-stimulated adrenal venous sampling but does not result in alterations in patient management.

Electrification of a Guidewire to Assist in Crossing an Aortic Coarctation (The BEACON Technique).

Aortic coarctation presents in adult life in a significant number of patients. The preferred treatment in this age group is percutaneous stent implantation without which life expectancy is reduced due to the complications of uncontrolled hypertension. We present the first case of an "uncrossable" aortic coarctation transversed using the BEACON (Brief Electrification of a guidewire to assist in crossing an Aortic CoarctatiON) technique, a novel approach incorporating the electrification of a guidewire. It requires standard transcaval equipment and techniques but crosses from aortic lumen-to-lumen instead of cava-to-aorta, thus creating a rail for successful stent delivery.

Joint UK societies' 2019 consensus statement on renal denervation.

Improved and durable control of hypertension is a global priority for healthcare providers and policymakers. There are several lifestyle measures that are proven to result in improved blood pressure (BP) control. Moreover, there is incontrovertible evidence from large scale randomised controlled trials (RCTs) that antihypertensive drugs lower BP safely and effectively in the long-term resulting in substantial reduction in cardiovascular morbidity and mortality. Importantly, however, evidence is accumulating to suggest that patients neither sustain long-term healthy behaviours nor adhere to lifelong drug treatment regimens and thus alternative measures to control hypertension warrant further investigation. Endovascular renal denervation (RDN) appears to hold some promise as a non-pharmacological approach to lowering BP and achieves renal sympathectomy using either radiofrequency energy or ultrasound-based approaches. This treatment modality has been evaluated in clinical trials in humans since 2009 but initial studies were compromised by being non-randomised, without sham control and small in size. Subsequently, clinical trial design and rigour of execution has been greatly improved resulting in recent sham-controlled RCTs that demonstrate short-term reduction in ambulatory BP without any significant safety concerns in both medication-naïve and medication-treated hypertensive patients. Despite this, the joint UK societies still feel that further evaluation of this therapy is warranted and that RDN should not be offered to patients outside of the context of clinical trials. This document reviews the updated evidence since our last consensus statement from 2014 and provides a research agenda for future clinical studies.

Adrenal Vein Catecholamine Levels and Ratios: Reference Intervals Derived from Patients with Primary Aldosteronism.

Phaeochromocytoma localisation is generally reliably achieved with modern imaging techniques, particularly in sporadic cases. On occasion, however, there can be diagnostic doubt due to the presence of bilateral adrenal abnormalities, particularly in patients with mutations in genes predisposing them to the development of multiple phaeochromocytomas. In such cases, surgical intervention is ideally limited to large or functional lesions due to the long-term consequences associated with hypoadrenalism. Adrenal venous sampling (AVS) for catecholamines has been used in this situation to guide surgery, although there are few data available to support diagnostic thresholds. Retrospective analyses of AVS results from 2 centres were carried out. A total of 172 patients (88 men, 84 women) underwent AVS under cosyntropin stimulation for the diagnosis of established primary aldosteronism (PA) with measurement of adrenal and peripheral venous cortisol, aldosterone and catecholamines. Six patients (3 men, 3 women) with phaeochromocytoma underwent AVS for diagnostic purposes with subsequent histological confirmation. Reference intervals for the adrenal venous norepinephrine to epinephrine ratio were created from the PA group. Using the 97.5th centile (1.21 on the left, 1.04 on the right), the false negative rate in the phaeochromocytoma group was 0%. In conclusion, this study describes the largest dataset of adrenal venous catecholamine measurements and provides reference intervals in patients without phaeochromocytoma. This strengthens the certainty with which conclusions related to adrenal venous sampling for catecholamines can be drawn, acknowledging the procedure is not part of the routine diagnostic workup and is an adjunct for use only in difficult clinical cases.

Long-term outcomes of children treated for Cushing's disease: a single center experience.

PURPOSE: Pediatric Cushing's disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients. METHODS: Retrospective review of 21 CD patients, mean age at diagnosis 12.1 years (5.7-17.8), managed in our center between 1986 and 2010. Mean follow-up from definitive treatment was 10.6 years (2.9-27.2). RESULTS: Fifteen patients were in remission following transsphenoidal surgery (TSS) and 5 were in remission following TSS + external pituitary radiotherapy (RT). One patient underwent bilateral adrenalectomy (BA). CD recurrence occurred in 3 (14.3 %) patients: 2 at 2 and 6 years after TSS and 1 7.6 years post-RT. The BA patient developed Nelson's syndrome requiring pituitary RT 0.6 years post-surgery. Short-term growth hormone deficiency (GHD) was present in 14 patients (81 % patients tested) (11 following TSS and 3 after RT) and 4 (44 % of tested) had long-term GHD. Gonadotropin deficiency caused impaired pubertal development in 9 patients (43 %), 4 requiring sex steroid replacement post-puberty. Four patients (19 %) had more than one pituitary hormone deficiency, 3 after TSS and 1 post-RT. Five patients (24 %) had long-term psychiatric co-morbidities (cognitive dysfunction or mood disturbance). There were significant long-term improvements in growth, weight and bone density but not complete reversal to normal in all patients. CONCLUSIONS: The long-term consequences of the diagnosis and treatment of CD in children is broadly similar to that seen in adults, with recurrence of CD after successful treatment uncommon but still seen. Pituitary hormone deficiencies occurred in the majority of patients after remission, and assessment and appropriate treatment of GHD is essential. However, while many parameters improve, some children may still have mild but persistent defects.

Joint UK societies' 2014 consensus statement on renal denervation for resistant hypertension.

Resistant hypertension continues to pose a major challenge to clinicians worldwide and has serious implications for patients who are at increased risk of cardiovascular morbidity and mortality with this diagnosis. Pharmacological therapy for resistant hypertension follows guidelines-based regimens although there is surprisingly scant evidence for beneficial outcomes using additional drug treatment after three antihypertensives have failed to achieve target blood pressure. Recently there has been considerable interest in the use of endoluminal renal denervation as an interventional technique to achieve renal nerve ablation and lower blood pressure. Although initial clinical trials of renal denervation in patients with resistant hypertension demonstrated encouraging office blood pressure reduction, a large randomised control trial (Symplicity HTN-3) with a sham-control limb, failed to meet its primary efficacy end point. The trial however was subject to a number of flaws which must be taken into consideration in interpreting the final results. Moreover a substantial body of evidence from non-randomised smaller trials does suggest that renal denervation may have an important role in the management of hypertension and other disease states characterised by overactivation of the sympathetic nervous system. The Joint UK Societies does not recommend the use of renal denervation for treatment of resistant hypertension in routine clinical practice but remains committed to supporting research activity in this field. A number of research strategies are identified and much that can be improved upon to ensure better design and conduct of future randomised studies.

Diagnosing unilateral primary aldosteronism - comparison of a clinical prediction score, computed tomography and adrenal venous sampling.

CONTEXT: In patients with primary aldosteronism (PA), adrenalectomy is potentially curative for those correctly identified as having unilateral excessive aldosterone production. It has been suggested that a recently developed and published clinical prediction score (CPS) may correctly identify some patients as having unilateral disease, without recourse to adrenal venous sampling. OBJECTIVE: We have applied the CPS to a large cohort of PA patients with defined and documented outcomes. We also incorporated a minor modification to the CPS and a radiological grading score (RGS) into our analysis to assess whether its performance could be augmented. RESULTS: A total of 75 patients with a robust diagnosis following bilateral adrenal venous cannulation and/or strictly defined surgical outcome were analysed. Applying the CPS to this group of patients produced a sensitivity of 38·8% and a specificity of 88·5% of correctly identifying unilateral aldosterone production. Using a suggested modification to the CPS, in which different levels of hypokalaemia were given different weightings, the sensitivity rose to 40·8%, with an identical specificity. Using the RGS alone improved sensitivity to 91·7%, but specificity was reduced to 62·5%. CONCLUSION: Applying the recently developed CPS to this cohort of patients, it was not possible to reproduce the 100% specificity reported in the original publication. Using the modified score or incorporating the RGS did not improve its performance. In this cohort, we were unable to show superiority of the CPS over an imaging-based strategy. CPS may have a role in guiding clinical decision-making, especially in those whose adrenal venous sampling (AVS) has been unsuccessful.

Endonasal endoscopic transsphenoidal pituitary surgery: early experience and outcome in paediatric Cushing's disease.

BACKGROUND: Selective adenomectomy remains the first-line treatment for Cushing's disease (CD), until recently by microscopic transsphenoidal pituitary surgery. Endonasal transsphenoidal endoscopic surgery (ETES) is emerging as a novel, less invasive treatment for pituitary adenomas and has become the optimal surgical approach. OBJECTIVE: There are no published series for the treatment of paediatric CD by ETES, and we report our centre's preliminary results. DESIGN: Retrospective analysis. PATIENTS: Six paediatric patients (median age 15·8 years; range 11·7-17·0 years) fulfilled standard diagnostic criteria for CD. Preoperatively, no abnormality was identified on pituitary MR scanning in 3 (50%) patients, one had a macroadenoma. Bilateral petrosal sinus sampling demonstrated central ACTH secretion (IPS/P ACTH ratio ≥3·0, post-CRH) in 3/6 (50%) patients. The same neurosurgeon and endoscopic nasal surgeon undertook all the operations. OUTCOME MEASURES: Therapeutic outcome and rate of complications. RESULTS: Clinical recovery and biochemical 'cure' were achieved in 5 (83%) patients, and a corticotroph adenoma was confirmed histologically in all cured cases. One case developed post-operative CSF leak requiring lumbar drain insertion and patching. At a mean interval of 4·7 years (0·1-10·8 years) post-operatively, cured patients have shown no recurrence. One patient, with a large diffuse adenoma requiring more extensive surgery, has panhypopituitarism, and another patient has GH and gonadotrophin deficiencies. CONCLUSIONS: Our experience shows that ETES for removing corticotroph adenomas in children, in most cases not visualized on MRI, is minimally invasive and gave excellent post-operative recovery/results. In skilled hands, this technique provides an alternative to conventional transsphenoidal microscopic surgery in managing paediatric CD.

Endovascular repair of symptomatic hemodialysis access graft pseudoaneurysms.

AIM: Repeated needle punctures of arteriovenous hemodialysis grafts can lead to the development of pseudoaneurysms. As they enlarge, graft pseudoaneurysms are associated with significant morbidity and require treatment. We present our single-center experience using stent grafts in selected patients to exclude symptomatic hemodialysis graft pseudoaneurysms. MATERIALS AND METHODS: Between March 2007 and December 2010, 11 consecutive patients (7 men and 4 women, mean age 57 years) underwent percutaneous endovascular repair of symptomatic hemodialysis access graft pseudoaneurysms. Indications for treatment were rapidly enlarging pseudoaneurysm in 5 patients, high venous pressures, limb edema and pseudoaneurysm in 3, skin breakdown over the pseudoaneurysm site in 2 and acute rupture and bleeding in 1 patient. No patient was lost to follow-up. RESULTS: Technical success across the 11 patients was 90.9%. The patient who presented with rupture required ligation of the access due to continuous bleeding after stent graft insertion. Balloon angioplasty of a separate hemodynamically significant stenosis at the time of stent graft insertion was performed in 7 of 11 (63.6%) patients. The primary access patency rates were 72.7% (95% CI of 0.390-0.939) at 3 months and 36.4% (95% CI 0.109-0.692) at 6 months. Secondary access patency rates were 72.7% at 6 months (95% CI 0.233-0.832). There were no procedure-related complications. Mean follow-up was 9 months (range 2-29 months). CONCLUSIONS: Endovascular treatment of symptomatic hemodialysis graft pseudoaneurysms is safe and effective with similar patency rates to surgical approaches. Importantly, this approach allows aggressive management of associated access circuit stenoses at the same time and avoids interval tunneled dialysis line insertion.

Differential diagnosis of adrenocorticotropic hormone-independent Cushing syndrome: role of adrenal venous sampling.

OBJECTIVE: To outline the potential role for adrenal venous sampling in the diagnosis and management of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS). METHODS: We present a case description and discuss the management of a 59-year-old woman with an 8-year history of weight gain, centripetal obesity, a round plethoric face, skin thinning, easy bruising, hirsutism, and progressive muscle weakness. RESULTS: The patient reported a prior personal history of asthma, type 2 diabetes mellitus, hypertension, dyslipidemia, and bilateral leg ulcers, but she denied having any personal or family history of endocrinopathy and was not taking any corticosteroid medication. Elevated midnight serum cortisol, failure to suppress cortisol levels with a low-dose dexamethasone suppression test, and undetectable plasma ACTH all indicated ACTH-independent CS. Additional investigations including dynamic tests and adrenal imaging were supported by adrenal venous sampling in order to make a diagnosis and formulate a management plan. She was ultimately noted to have bilateral functioning adrenal nodules (adenoma and adenolipoma) and underwent successful bilateral laparoscopic adrenalectomy, with postoperative glucocorticoid and mineralocorticoid replacement. CONCLUSION: Adrenal venous sampling may be an important step in the differential diagnosis of CS and localization of the source of cortisol excess. It may distinguish pheochromocytoma or benign nonfunctioning adrenal nodules from cortisol-secreting adenomas and may avoid unnecessary bilateral adrenalectomy. It can also ensure that the correct operation is completed, if required, and thus avoid the increased morbidity and mortality associated with repeated surgical interventions.

A prospective evaluation of postural stimulation testing, computed tomography and adrenal vein sampling in the differential diagnosis of primary aldosteronism.

CONTEXT: In primary aldosteronism (PA), discriminating unilateral from bilateral disease is crucial because adrenalectomy is frequently curative in the former case but rarely helps in the latter. Various series have reported the utility of postural stimulation testing (PST), cross-sectional imaging and adrenal vein sampling (AVS) in the assessment of PA, but most of these studies were retrospective. OBJECTIVE: To prospectively determine the diagnostic utility of PST, AVS and computed tomography (CT) using a radiological scoring system in the assessment of PA in a tertiary centre, as well as to document the incidence of autonomous cortisol cosecretion. DESIGN AND SETTING: Fifty consecutive patients with PA underwent PST, CT, AVS and a low-dose dexamethasone suppression test with measurement of serum cortisol at 48 h. For patients who underwent surgery, histological confirmation, and a normal postoperative serum aldosterone concentration and plasma renin activity were taken as evidence for unilateral disease. For other patients, results from successful adrenal vein sampling were the diagnostic evidence against which CT and PST were assessed. RESULTS: Postural stimulation testing had a sensitivity and specificity of 44-56% and 71-75%, respectively. CT had an overall sensitivity and specificity of 77% and 80%, respectively, rising to 100% sensitivity and specificity if there was a single, discrete macronodule with an unequivocally normal contralateral gland. Evidence of cosecretion of cortisol occurred in 14% of patients. CONCLUSIONS: Preliminary experience is presented of an objective radiological scoring system for selecting patients with PA for AVS. PST provides little, if any, useful additional information. A significant minority of patients with PA exhibit evidence of cortisol cosecretion, which may have implications for perioperative management.

The role of interventional venous sampling in localising neuroendocrine tumours.

PURPOSE OF REVIEW: This review focuses on the role of interventional venous sampling in the diagnosis and localization of neuroendocrine tumours (NETs), and its role in relation to conventional and novel imaging techniques. RECENT FINDINGS: Imaging of NETs has evolved together with advances in imaging technology. Imaging localization plays an important role in the subsequent management of these tumours. This article provides an overview of the application of venous sampling in the localization of NETs, presented with current evidence to support its continued role in the diagnostic work-up of pituitary, parathyroid, pancreatic, adrenal and ovarian endocrine disease. SUMMARY: Interventional venous sampling continues to be a highly sensitive modality in the localization of NETs. Although significant advances in noninvasive anatomic and functional imaging modalities have reduced the reliance of this well established technique, the latest literature continues to support its important role in the diagnostic armament of these unique and rare tumours.

Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation.

CONTEXT: Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging. OBJECTIVE: To review diagnostic features and localisation accuracy for insulinomas. DESIGN: Cross-sectional, retrospective analysis. SETTING: A single tertiary referral centre. PATIENTS: Patients with insulinoma in the years 1990-2009, including sporadic tumours and those in patients with multiple endocrine neoplasia syndromes. INTERVENTIONS: Patients were identified from a database, and case notes and investigation results were reviewed. Tumour localisation by computed tomography (CT), magnetic resonance imaging (MRI), octreotide scanning, endoscopic ultrasound (EUS) and calcium stimulation was evaluated. MAIN OUTCOME MEASURE(S): Insulinoma localisation was compared to histologically confirmed location following surgical excision. RESULTS: Thirty-seven instances of biochemically and/or histologically proven insulinoma were identified in 36 patients, of which seven were managed medically. Of the 30 treated surgically, 25 had CT (83.3%) and 28 had MRI (90.3%), with successful localisation in 16 (64%) by CT and 21 (75%) by MRI respectively. Considered together, such imaging correctly localised 80% of lesions. Radiolabelled octreotide scanning was positive in 10 out of 20 cases (50%); EUS correctly identified 17 lesions in 26 patients (65.4%). Twenty-seven patients had calcium stimulation testing, of which 6 (22%) did not localise, 17 (63%) were correctly localised, and 4 (15%) gave discordant or confusing results. CONCLUSIONS: Preoperative localisation of insulinomas remains challenging. A pragmatic combination of CT and especially MRI predicts tumour localisation with high accuracy. Radionuclide imaging and EUS were less helpful but may be valuable in selected cases. Calcium stimulation currently remains useful in providing an additional functional perspective.

Diagnosis and treatment of Cushing's disease in children.

Cushing's disease (CD) is rare in the paediatric age range, but presents a diagnostic and therapeutic challenge. Most paediatric endocrinologists have limited experience managing children or adolescents with CD and thus benefit from close consultation with adult colleagues. A diagnostic protocol for investigation is required which broadly follows the model for adult patients. Treatment strategies for CD are described and critically appraised. The management of paediatric CD patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life.

Multiple intrahepatic artery aneurysms in a patient with Behçet's disease: use of transcatheter embolization for rupture.

Intrahepatic artery aneuryms are a rare and potentially life-threatening condition. We present the first case in the English literature of multiple intrahepatic artery aneuryms in a patient with Behçet's disease who presented acutely with rupture. The ruptured aneurysm was treated successfully with transcatheter arterial coil embolization-CT and clinical follow-up confirming a good result. We discuss the management dilemma with regard to prophylactic embolization of the numerous other small asymptomatic intrahepatic aneurysms in this same patient.

Total percutaneous aortic repair: midterm outcomes.

The purpose of this study was to examine the immediate and midterm outcomes of percutaneous endovascular repair of thoracic and abdominal aortic pathology. Between December 2003 and June 2005, 21 patients (mean age: 60.4 +/- 17.1 years; 15 males, 6 females) underwent endovascular stent-graft insertion for thoracic (n = 13) or abdominal aortic (n = 8) pathology. Preprocedural computed tomographic angiography (CTA) was performed to assess the suitability of aorto-iliac and common femoral artery (CFA) anatomy, including the degree of CFA calcification, for total percutaneous aortic stent-graft repair. Percutaneous access was used for the introduction of 18- to 26-Fr delivery devices. A 'preclose' closure technique using two Perclose suture devices (Perclose A-T; Abbott Vascular) was used in all cases. Data were prospectively collected. Each CFA puncture site was assessed via clinical examination and CTA at 1, 6, and 12 months, followed by annual review thereafter. Minimum follow-up was 36 months. Outcome measures evaluated were rates of technical success, conversion to open surgical repair, complications, and late incidence of arterial stenosis at the site of Perclose suture deployment. A total of 58 Perclose devices were used to close 29 femoral arteriotomies. Outer diameters of stent-graft delivery devices used were 18 Fr (n = 5), 20 Fr (n = 3), 22 Fr (n = 4), 24 Fr (n = 15), and 26 Fr (n = 2). Percutaneous closure was successful in 96.6% (28/29) of arteriotomies. Conversion to surgical repair was required at one access site (3.4%). Mean follow-up was 50 +/- 8 months. No late complications were observed. By CT criteria, no patient developed a >50% reduction in CFA caliber at the site of Perclose deployment during the study period. In conclusion, percutaneous aortic stent-graft insertion can be safely performed, with a low risk of both immediate and midterm access-related complications.