Neena Natt

Surgery for Cushing’s Syndrome: An Historical Review and Recent Ten-year Experience

BackgroundCushing’s syndrome (CS), due to multiple etiologies, is a disorder associated with the ravages of cortisol excess. The purpose of this review article is to provide a historical synopsis of surgery for CS, review a recent 10-year period of operative management at a tertiary care facility, and to outline a practical approach to diagnosis and management.Materials and MethodsFrom 1996 to 2005, 298 patients underwent 322 operative procedures for CS at Mayo Clinic, Rochester, Minnesota. A retrospective chart review was carried out. Data was gathered regarding demographics, preoperative assessment, procedures performed, and outcomes. Data are presented as counts and percentages. Five-year survival rates were calculated where applicable by the Kaplan-Meier method. Statistical analysis was carried out with SAS, version 9 (SAS Institute, Inc., Cary, NC).ResultsTwo-hundred thirty-one patients (78%) had ACTH-dependent CS and 67 patients (22%) had ACTH-independent CS. One-hundred ninety-six patients (66%) had pituitary-dependent CS and 35 patients (12%) had ectopic ACTH syndrome. Fifty-four patients (18%) had cortisol-secreting adenomas, 10 patients (3%) had cortisol-producing adrenocortical carcinomas, and 1% had other causes. Cure rates for first time pituitary operations (transsphenoidal, sublabial, and endonasal) were 80% and 55% for reoperations. Most benign adrenal processes could be managed laparoscopically. Five-year survival rates (all causes) were 90%, 51%, and 23% for adrenocortical adenomas, ectopic ACTH syndrome, and adrenocortical carcinomas, respectively.ConclusionsSurgery for CS is highly successful for pituitary-dependent CS and most ACTH-independent adrenal causes. Bilateral total adrenalectomy can also provide effective palliation from the ravages of hypercortisolism in patients with ectopic ACTH syndrome and for those who have failed transsphenoidal surgery. Unfortunately, to date, adrenocortical carcinomas are rarely cured. Future successes with this disease will likely depend on a better understanding of tumor biology, more effective adjuvant therapies and earlier detection. Clearly, IPSS, advances in cross-sectional imaging, along with developments in transsphenoidal and laparoscopic surgery, have had the greatest impact on today’s management of the complex patient with CS.

Validity evidence for an OSCE to assess competency in systems-based practice and practice-based learning and improvement: a preliminary investigation.

Purpose To determine the psychometric properties and validity of an OSCE to assess the competencies of Practice-Based Learning and Improvement (PBLI) and Systems-Based Practice (SBP) in graduate medical education. Method An eight-station OSCE was piloted at the end of a three-week Quality Improvement elective for nine preventive medicine and endocrinology fellows at Mayo Clinic. The stations assessed performance in quality measurement, root cause analysis, evidence-based medicine, insurance systems, team collaboration, prescription errors, Nolan’s model, and negotiation. Fellows’ performance in each of the stations was assessed by three faculty experts using checklists and a five-point global competency scale. A modified Angoff procedure was used to set standards. Evidence for the OSCE’s validity, feasibility, and acceptability was gathered. Results Evidence for content and response process validity was judged as excellent by institutional content experts. Interrater reliability of scores ranged from 0.85 to 1 for most stations. Interstation correlation coefficients ranged from −0.62 to 0.99, reflecting case specificity. Implementation cost was approximately

Body composition and quality of life in adults treated with GH therapy: a systematic review and meta-analysis.

255 per fellow. All faculty members agreed that the OSCE was realistic and capable of providing accurate assessments. Conclusions The OSCE provides an opportunity to systematically sample the different subdomains of Quality Improvement. Furthermore, the OSCE provides an opportunity for the demonstration of skills rather than the testing of knowledge alone, thus making it a potentially powerful assessment tool for SBP and PBLI. The study OSCE was well suited to assess SBP and PBLI. The evidence gathered through this study lays the foundation for future validation work.

ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis

OBJECTIVE To summarise the evidence about the efficacy and safety of using GH in adults with GH deficiency focusing on quality of life and body composition. DATA SOURCES We searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus through April 2011. We also reviewed reference lists and contacted experts to identify candidate studies. STUDY SELECTION Reviewers, working independently and in duplicate, selected randomised controlled trials (RCTs) that compared GH to placebo. DATA SYNTHESIS We pooled the relative risk (RR) and weighted mean difference (WMD) by the random effects model and assessed heterogeneity using the I(2) statistic. RESULTS Fifty-four RCTs were included enrolling over 3400 patients. The quality of the included trials was fair. GH use was associated with statistically significant reduction in weight (WMD, 95% confidence interval (95% CI): -2.31 kg, -2.66 and -1.96) and body fat content (WMD, 95% CI: -2.56 kg, -2.97 and -2.16); increase in lean body mass (WMD, 95% CI: 1.38, 1.10 and 1.65), the risk of oedema (RR, 95% CI: 6.07, 4.34 and 8.48) and joint stiffness (RR, 95% CI: 4.17, 1.4 and 12.38); without significant changes in body mass index, bone mineral density or other adverse effects. Quality of life measures improved in 11 of the 16 trials although meta-analysis was not feasible. RESULTS GH therapy in adults with confirmed GH deficiency reduces weight and body fat, increases lean body mass and increases oedema and joint stiffness. Most trials demonstrated improvement in quality of life measures.

Sublabial Transseptal vs Transnasal Combined Endoscopic Microsurgery in Patients With Cushing Disease and MRI-Depicted Microadenomas

CONTEXT The diagnosis of adrenal insufficiency is clinically challenging and often requires ACTH stimulation tests. OBJECTIVE To determine the diagnostic accuracy of the high- (250 mcg) and low- (1 mcg) dose ACTH stimulation tests in the diagnosis of adrenal insufficiency. METHODS We searched six databases through February 2014. Pairs of independent reviewers selected studies and appraised the risk of bias. Diagnostic association measures were pooled across studies using a bivariate model. DATA SYNTHESIS For secondary adrenal insufficiency, we included 30 studies enrolling 1209 adults and 228 children. High- and low-dose ACTH stimulation tests had similar diagnostic accuracy in adults and children using different peak serum cortisol cutoffs. In general, both tests had low sensitivity and high specificity resulting in reasonable likelihood ratios for a positive test (adults: high dose, 9.1; low dose, 5.9; children: high dose, 43.5; low dose, 7.7), but a fairly suboptimal likelihood ratio for a negative test (adults: high dose, 0.39; low dose, 0.19; children: high dose, 0.65; low dose, 0.34). For primary adrenal insufficiency, we included five studies enrolling 100 patients. Data were only available to estimate the sensitivity of high dose ACTH stimulation test (92%; 95% confidence interval, 81-97%). CONCLUSION Both high- and low-dose ACTH stimulation tests had similar diagnostic accuracy. Both tests are adequate to rule in, but not rule out, secondary adrenal insufficiency. Our confidence in these estimates is low to moderate because of the likely risk of bias, heterogeneity, and imprecision.

3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing's syndrome

OBJECTIVE To assess whether the type of surgical approach to the sella (sublabial transseptal vs transnasal) affects surgical outcome among patients with Cushing disease. PARTICIPANTS AND METHODS Both procedures were performed at our institution from January 1, 1995, through January 31, 2003. From a total of 106 patients with Cushing disease who had had surgery, we identified 42 adults undergoing an initial surgery, with microadenoma (<1 cm) determined by magnetic resonance imaging and a minimal follow-up of 3 months. RESULTS We identified 21 patients (4 male, 17 female) for sublabial transseptal transsphenoidal microsurgery. Mean+/-SD age was 45.0+/-12.9 years (range, 27.0-69.0 years); median duration of symptoms was 2.5 years (range, 1.5-7.5 years). Median follow-up was 1.0 year (range, 0.3-11.0 years). We identified another 21 patients (5 male, 16 female) for endoscopic transsphenoidal microsurgery whose mean+/-SD age was 43.8+/-14.1 years (range, 19.0-70.0 years); median duration of symptoms was 2.4 years (range, 0.2-6.0 years). Median follow-up was 2.5 years (range, 0.3-8.7 years). Complications (cerebrospinal fluid leak and transient diabetes insipidus) and cure (86% initial cure; 76% relapse-included cure) were equivalent between the 2 procedures. However, the endoscopic approach was associated with shorter anesthesia time, less blood loss, and shorter hospital stays. CONCLUSION The endoscopic transnasal surgical approach led to shorter total anesthesia time, less blood loss, and shorter hospital stay when compared with the sublabial transseptal approach. However, we found no difference between the 2 surgical procedures with respect to cure or complications, suggesting that outcome is more closely related to the experience of the operating team.

Stereotactic management of craniopharyngiomas.

Objective  We sought to determine if higher resolution 3 Tesla (T) magnetic resonance imaging (MRI) with or without ovine corticotropin releasing hormone (o‐CRH) stimulation would increase the sensitivity for detection of pituitary microadenomas in ACTH‐dependent Cushing’s syndrome (CS).

Extracervical fibrosclerosis causing obstruction of a ventriculo-peritoneal shunt in a patient with hydrocephalus and invasive fibrous thyroiditis (Riedel's struma)

Eleven patients with craniopharyngiomas underwent 13 stereotactic procedures (intracavitary irradiation, n = 7; radiosurgery, n = 6). Nine patients (82%) had recurrent tumors after prior surgery (median, 2 operations). The median patient age was 50 years (range, 6–63 years). At a median follow-up of 38 months (range, 24–102 months), no patient had progression of the treated tumor component. Two patients developed new cysts, so the actuarial 2- and 4-year progression-free survival rates were 91 and 73%, respectively. Visual function improved in 3 patients, remained stable in 6 patients, and worsened in 1 patient. Two patients (both without prior surgery) not having diabetes insipidus pre-operatively continued to have normal posterior pituitary function. Stereotactic techniques should be considered for patients with craniopharyngiomas, especially those who have failed prior surgical resection.

THE OVINE CORTICOTROPIN-RELEASING HORMONE STIMULATION TEST IN THE DIFFERENTIAL DIAGNOSIS OF ADRENOCORTICOTROPIC HORMONE-DEPENDENT CUSHING'S SYNDROME

The association of invasive fibrous thyroiditis (IFT) with foci of extracervical fibrosclerosis is well recognized. Affected sites include the retroperitoneum, the mediastinum, the biliary tract, and the orbit. The development of subcutaneous fibrosclerosis, however, is extremely rare. We report a patient with known invasive fibrous thyroiditis and hypoparathyroidism who presented with localized subcutaneous fibrosclerosis of the anterior chest wall resulting in compression of his ventriculoperitoneal shunt. The aetiology of IFT has remained unclear. Several histological and serological features, including the presence of mononuclear cells within the fibrosclerotic process, the occurrence of microscopic vasculitis, and the detection of autoantibodies directed against thyroid‐specific antigens in a large proportion of patients with IFT, currently support the notion of autoimmune mechanisms playing a role in the pathogenesis of this rare disease.

THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis

OBJECTIVE To determine the efficacy of the ovine corticotropin-releasing hormone (oCRH) stimulation test in distinguishing between adrenocorticotropic hormone (ACTH)-dependent types of Cushings syndrome. METHODS The cortisol and ACTH responses to intravenously administered oCRH were determined in 64 patients with pituitary-dependent Cushings syndrome and 13 patients with ectopic ACTH production. RESULTS Of the 64 patients with pituitary-dependent Cushings syndrome, 57 (89%) had a positive ACTH response to administration of oCRH (an increase of 50% or more above baseline), and 56 (88%) had a positive cortisol response (an increase of 20% or more above baseline). One patient with an ectopic ACTH-secreting tumor had a false-positive cortisol response to administration of oCRH. Two patients with ectopic ACTH-secreting tumors had false-positive responses to both ACTH and cortisol after oCRH was administered. Because both these patients did not have hypercortisolemia at the time of testing, they were excluded from the statistical analysis. When analyzed on the basis of ACTH response alone, oCRH testing yielded a diagnostic sensitivity and specificity for the diagnosis of pituitary-dependent hypercortisolism of 89% and 100%, respectively. The positive predictive value was 100%, and the negative predictive value was 61%. CONCLUSION oCRH testing distinguished between the ectopic ACTH syndrome and pituitary-dependent hyper-cortisolism in most cases. Therefore, this test is a useful procedure in the diagnostic evaluation of ACTH-dependent forms of Cushings syndrome.