Clinical and imaging presentations are associated with function in incidental adrenocortical adenomas: a retrospective cohort study.

OBJECTIVE: The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs). DESIGN: This is a single-center cohort study. METHODS: Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016. RESULTS: Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 µg/dL, P = .002). CONCLUSIONS: Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.

The role of weight bias and role-modeling in medical students' patient-centered communication with higher weight standardized patients.

OBJECTIVE: Patients with obesity may experience less patient-centered care. We assessed whether medical students' implicit/explicit weight-related attitudes and perceptions of normative attitudes are associated with patient-centered care for patients with obesity. METHODS: Third and fourth year medical students (N = 111) at one medical school completed a survey and participated in a patient care scenario with a standardized patient with obesity. Encounters were coded for patient-centered behavior. Predictors of patient-centered behaviors were assessed. RESULTS: Student perceptions that negative attitudes about patients with obesity are normative in medical school were significantly associated with poorer patient-centered behaviors, including lower attentiveness (b=-0.19, p = 0.01), friendliness (b=-0.28, p < 0.001), responsiveness (b=-0.21, p = 0.002), respectfulness (b=-0.17, p = 0.003), interactivity (b=-0.22, p = 0.003), likelihood of being recommended by observers (b=-0.34, p < 0.001), and patient-centeredness index scores (b=-0.16, p = 0.002). Student reported faculty role-modeling of discrimination against patients with obesity predicted lower friendliness (b=-0.16, p = 0.03), recommendation likelihood (b=-0.22, p = 0.04), and patient-centeredness index score (b=-0.12, p = 0.03). CONCLUSIONS: Negative normative attitudes and behaviors regarding obesity in the medical school environment may adversely influence the quality of patient-centered behaviors provided to patients with obesity. PRACTICE IMPLICATIONS: Efforts to improve patient-centered communication quality among medical trainees may benefit from intervention to improve group normative attitudes about patients with obesity.

Promoting Value Through Patient-Centered Communication: A Multisite Validity Study of Third-Year Medical Students.

PURPOSE: To examine validity evidence for a standardized patient scenario assessing medical students' ability to promote value using patient-centered communication (in response to a patient requesting an unnecessary test) and to explore the potential effect of various implementation and curricular factors on student scores. METHOD: Third-year medical students (N = 516) from 5 U.S. MD-granting medical schools completed the communication scenario between 2014 and 2017 as part of a larger objective structured clinical examination (OSCE). Centralized raters assessed performance using an 11-item checklist. The authors collected multiple sources of validity evidence. RESULTS: The mean checklist score was 0.85 (standard deviation 0.09). Interrater reliability for checklist scores was excellent (0.87, 95% confidence interval = 0.78-0.93). Generalizability and Phi-coefficients were, respectively, 0.65 and 0.57. Scores decreased as the number of OSCE stations increased (r = -0.15, P = .001) and increased when they were used for summative purposes (r = 0.26, P < .001). Scores were not associated with curricular time devoted to high-value care (r = 0.02, P = .67) and decreased when more clerkships were completed before the assessment (r = -0.12, P = .006). CONCLUSIONS: This multisite study provides validity evidence supporting the use of scenario scores to assess the ability of medical students to promote value in clinical encounters using patient-centered communication. Findings illuminate the potential effect of OSCE structure and purpose on student performance and suggest clerkship learning experiences may not reinforce what students are taught in the formal curriculum regarding high-value care. Devoting more time to the topic appears insufficient to counteract this erosion.

MANAGEMENT AND OUTCOMES OF GIANT PROLACTINOMA: A SERIES OF 71 PATIENTS.

Objective: To describe outcomes of patients with giant prolactinoma (≥4 cm) and identify predictors of therapeutic response. Methods: In this retrospective study, complete biochemical and structural response were defined as prolactin (PRL) ≤25 ng/mL and no visible tumor at follow-up, respectively. Results: Giant prolactinoma (median size, 4.8 cm [range, 4 to 9.8 cm]; median PRL, 5,927 ng/mL [range, 120 to 100,000 ng/mL]) was diagnosed in 71 patients. Treatments included: dopamine agonists (DAs) (n = 70, 99%), surgery (n = 30, 42%), radiation (n = 10, 14%), and somatostatin analogs (n = 2, 3%). Patients treated with DA monotherapy were older compared with those who received subsequent therapies (47 years vs. 28 years; P = .003) but had similar initial PRL and tumor size. Surgically managed patients were younger compared with the nonsurgical group (35 years vs. 46 years; P = .02) and had lower initial PRL (3,121 ng/mL vs. 6,920 ng/mL; P = .02), yet they had similar tumor response. Hypopituitarism was more common following surgery compared to medical management: adrenal insufficiency (69% vs. 27%; P<.001), hypothyroidism (67% vs. 38%; P = .02), growth hormone deficiency (24% vs. 6%; P = .04), and diabetes insipidus (17% vs. 3%; P = .04). Therapeutic response did not correlate with sex, age, initial PRL, tumor size, or first-line therapy mode. At median follow-up of 4.8 years, the median PRL was 18.3 ng/mL (range, 0.6 to 12,680 ng/mL), and final volume was 0.9 cm3 (range, 0 to 43.0 cm3). In those with available data, 36/65 (55%) patients achieved PRL normalization, and 16/61 (26%) had no visible tumor at follow-up. Conclusion: Most patients with giant prolactinoma have excellent response to DA. Sex, age, initial PRL, and tumor size do not predict therapeutic response. Abbreviations: BRC = bromocriptine; CAB = cabergoline; CSF = cerebrospinal fluid; DA = dopamine agonist; MRI = magnetic resonance imaging; PRL = prolactin.

ENDOCRINOLOGY FELLOWS' PERCEPTION OF THEIR CONFIDENCE AND SKILL LEVEL IN PROVIDING TRANSGENDER HEALTHCARE.

OBJECTIVE: Both educational content and hours devoted to transgender health training of endocrinology fellows are suboptimal. The objective of this study was to assess the perspectives of endocrinology fellows on their training in transgender health. METHODS: We evaluated the state of comfort and knowledge of transgender healthcare among endocrinology fellows attending Endocrine University. Surveys were administered to fellows before and after their participation in a case-based session on transgender health. RESULTS: The majority of fellows felt that training in transgender health is important (95.9%, 189/197); however, only 58.9% reported inclusion of dedicated transgender content in their training programs. Fellows who had received transgender healthcare education, and those who had seen more transgender patients in their training, were more likely to be confident in treating patients with hormone therapy ( P<.001 and P<.0001, respectively). Following the case-based session, 62.4 % of fellows reported that they would change their practice, 72.8% felt that their comfort level with transgender care had improved, and 91% felt that transgender content such as that provided in the educational session should be mandatory in endocrinology training programs. Methods most desired by fellows to improve their education included lectures from visiting professors (70.3%), participation in elective rotations (62.1%), online training modules (57.9%), and attendance at meetings with transgender topics (57.4%). CONCLUSION: Transgender health education of U.S. endocrinology fellows is suboptimal. Participation in a case-based session significantly increased the comfort level of endocrinology fellows in key areas of transgender health. Abbreviation: ACGME = Accreditation Council for Graduate Medical Education.

Extensive clinical experience: Hypothalamic-pituitary-adrenal axis recovery after adrenalectomy for corticotropin-independent cortisol excess.

OBJECTIVE: To identify predictors of hypothalamic-pituitary-adrenal (HPA) axis recovery interval and severity of glucocorticoid withdrawal symptoms (GWS) in patients undergoing adrenalectomy for corticotropin-independent cortisol excess. DESIGN: This is a retrospective study of patients with mild autonomous cortisol excess (MACE), moderate and severe Cushing syndrome (CS) who developed adrenal insufficiency after unilateral adrenalectomy between 1998 and 2017. RESULTS: Adrenalectomy was performed in 81 patients (79% women, median age 52 years [IQR 42-62]). HPA axis recovery occurred at a median of 4.3 months (IQR 1.6-11.4) after adrenalectomy (severe CS vs moderate CS vs MACE: median 11.4 vs 2.8 vs 2.1 months, P < 0.01). Main predictors of HPA axis recovery interval included: preoperative serum cortisol concentration after 1-mg overnight dexamethasone suppression test >10 µg/dL or >276 nmol/L (9.7 vs 1.3 months if cortisol ≤10 µg/dL or ≤276 nmol/L, P < 0.01); body mass index (for every 3 kg/m2 decrease, glucocorticoid taper increased by 1 month, P < 0.05); age <45 (11.4 vs 2.3 months if ≥45 years, P < 0.05); duration of symptoms prior to diagnosis >1 year (11.4 vs 2.8 months if ≤1 year); moon facies (11.4 vs 2.2 months if no rounding of the face); and myopathy (13.1 vs 2.7 months if no myopathy, P < 0.05). Patients with severe CS had a higher incidence of GWS compared to patients with MACE (66.7% vs 40.0%, P < 0.05) with a median of 1 and 0 events/patient, respectively. CONCLUSIONS: The HPA axis recovery interval was the longest for patients with severe CS. Surprisingly, patients with moderate CS recovered their HPA axis as quickly as those with MACE. Glucocorticoid withdrawal symptoms were observed in all groups, with more events in patients with severe CS. This study emphasizes the need to counsel patients on expectations for HPA axis recovery and address intervention for GWS based on individual preoperative parameters.

NECESSITY OF MULTIMODAL TREATMENT OF ACROMEGALY AND OUTCOMES.

OBJECTIVE: Uncontrolled acromegaly is associated with increased morbidity and mortality. Despite multimodal therapeutic options, adequate control can be challenging and lead to prolonged exposure to growth hormone excess. The aim of this study was to assess treatment patterns and outcomes in patients with acromegaly following surgery at a single institution. METHODS: A retrospective analysis of response to treatment modalities for patients with a new diagnosis of acromegaly at the Mayo Clinic in Rochester, Minnesota, from 1995-2015. RESULTS: A total of 245 patients with newly diagnosed acromegaly (mean age at diagnosis, 47 ± 14 years; mean follow-up, 5.5 ± 5 years) were evaluated. Primary surgical intervention was performed in 236 patients; 117 (54%) did not achieve remission. Among those with ≥3 months follow-up, 76/217 (35%) patients required three or more forms of treatment. Mean tumor size at diagnosis was 1.6 ± 0.8 cm (80% macroadenomas), and 35% (75/217) had cavernous sinus invasion on pre-operative imaging. The most common second-line treatment was radiation treatment (RT) (50%, 59/117). Among those with persistent disease following surgery, a normal insulin-like growth factor 1 (IGF-1) was achieved in 52% (61/117), with a median time to acromegaly control of 4.5 years. The rate of IGF-1 normalization was 2.1-fold higher in those who received RT compared to those who did not. CONCLUSION: In patients with persistent acromegaly following surgery, multiple treatment modalities, including RT, may be required to achieve remission. Treatment outcome uncertainty and the need for multiple interventions add to the disease burden associated with persistent acromegaly. ABBREVIATIONS: CI = confidence interval; GH = growth hormone; IGF-1 = insulin like growth factor-1; KM = Kaplan-Meier; RT = radiation treatment.

High-Value, Cost-Conscious Communication Skills in Undergraduate Medical Education: Validity Evidence for Scores Derived from Two Standardized Patient Scenarios.

INTRODUCTION: Training in high-value, cost-conscious care (HVCCC) is increasingly being incorporated into medical school curricula, but students may have limited opportunities to engage patients in HVCCC conversations. The aim of this study was to develop two standardized patient scenarios with associated checklists, hypothesizing that resulting scores would allow for valid formative assessments of HVCCC communication skills. METHODS: Scenarios were designed to generate a less-is-more conversation (in response to a patient requesting an unnecessary test) and a shared decision-making conversation (in response to a patient choosing between multiple effective treatment options). Checklists were developed by experts and informed by the existing literature. Validity evidence was collected from content, response process, internal structure, relations to other variables, and consequences of testing. RESULTS: Ninety-three third-year medical students participated during 2014-2015. Mean checklist scores were 79% (SD = 18, Cronbach α = 0.72) and 72% (SD = 13, Cronbach α = 0.62) for the less-is-more and shared decision-making scenarios, respectively. Checklist scores correlated with global ratings of performance (r = 0.65 and 0.54, respectively, both P < 0.001), and overall interrater reliability was good (r = 0.66). Checklist scores discriminated between higher and lower performers (discrimination indices of 0.84 and 0.65, respectively, both P < 0.001). Most students (83/90, 92%) agreed that the session improved their HVCCC communication skills. CONCLUSIONS: This study provides validity evidence supporting the use of scores derived from two standardized patient scenarios for formative assessment of HVCCC communication skills among third-year medical students. These scenarios can help equip students with practical, patient-centered strategies for promoting value in clinical encounters.

Diagnostic performance of unenhanced computed tomography and 18 F-fluorodeoxyglucose positron emission tomography in indeterminate adrenal tumours.

OBJECTIVE: Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18 F-fluorodeoxyglucose (18 FDG) positron emission tomography (PET)/CT imaging in a high-risk population for adrenal malignancy using an optimal reference standard. DESIGN: Retrospective cohort study. METHODS: Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy. RESULTS: Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (-21-78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18 FDG-PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7-9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74-13.4] vs 1.2 [0.5-6.6], respectively, P<.0001). 18 FDG-PET/CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%. CONCLUSION: Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high-risk population. For indeterminate adrenal lesions, given a superior specificity, 18 FDG-PET/CT could be considered as a second stage imaging study.

Transgender Health in Endocrinology: Current Status of Endocrinology Fellowship Programs and Practicing Clinicians.

Context: The transgender population continues to face challenges in accessing appropriate health care. Adequate training of endocrinologists in this area is a priority. Objectives: Assess the status of transgender health care education in US endocrinology fellowship training programs and assess knowledge and practice of transgender health among practicing US endocrinologists. Design: Mayo Clinic and the Endocrine Society developed and administered a Web-based anonymous survey to 104 endocrinology fellowship program directors (PDs; members of the Association of Program Directors in Endocrinology, Diabetes and Metabolism) and 6992 US medical doctor members of Endocrine Society. Results: There were 54 total responses from 104 PDs (51.9%). Thirty-five of these 54 programs (72.2%) provide teaching on transgender health topics; however, 93.8% respondents indicated that fellowship training in this area is important. Barriers to provision of education included lack of faculty interest or experience. The most desired strategies to increase transgender-specific content included online training modules for trainees and faculty. Of 411 practicing clinician responders, almost 80% have treated a transgender patient, but 80.6% have never received training on care of transgender patients. Clinicians were very or somewhat confident in terms of definitions (77.1%), taking a history (63.3%), and prescribing hormones (64.8%); however, low confidence was reported outside of the hormonal realm. The most requested methods of education included online training modules and presentation of transgender topics at meetings. Conclusions: Confidence and competence in transgender health needs to increase among endocrinologists. Strategies include the development of online training modules, expansion of formal transgender curricula in fellowship programs, and presentations at national and international meetings.

Science of Health Care Delivery: An Innovation in Undergraduate Medical Education to Meet Society's Needs.

The purpose of this special article is to describe a new, 4-year Science of Health Care Delivery curriculum at Mayo Clinic School of Medicine, including curricular content and structure, methods for instruction, partnership with Arizona State University, and implementation challenges. This curriculum is intended to ensure that graduating medical students enter residency prepared to train and eventually practice within person-centered, community- and population-oriented, science-driven, collaborative care teams delivering high-value care. A Science of Health Care Delivery curriculum in undergraduate medical education is necessary to successfully prepare physicians so as to ensure the best clinical outcomes and patient experience of care, at the lowest cost.

GLUCOCORTICOID REPLACEMENT REGIMENS IN CHRONIC ADRENAL INSUFFICIENCY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: Various glucocorticoid (GC) regimens have been used in the treatment of patients with adrenal insufficiency, yet the differences between such regimens on health outcomes are unclear. We performed a systematic review and meta-analysis to compare the effects of GC regimens on quality of life (QoL), bone density, incidence of adrenal crisis, and death. In pediatric studies, we also searched for final adult height. METHODS: We searched 6 databases through July 2016. Studies were selected and appraised by independent reviewers. Data were pooled using the profile likelihood random-effects model. RESULTS: We included 34 studies. We found no difference in QoL scores between higher (≥30 mg/day of hydrocortisone [HC] equivalence) vs. lower daily doses (<30 mg/day of HC equivalence) (P = .15) or based on frequency of daily dosing (once, twice or thrice daily). Extended-release (1 study), dual-/modified-release (3 studies), and continuous subcutaneous (3 studies) forms of GCs were associated with higher QoL scores. There was no significant association between dose and type of GC and the incidence of adrenal crises. The effect on bone mineral density was heterogeneous. No data were available on mortality or final adult height in children. The quality of evidence was low due to increased risk of bias, imprecision, and heterogeneity. CONCLUSION: Extended-/dual-release, and continuous subcutaneous forms of GC may be associated with higher QoL scores. However, this is derived from short-term and imprecise evidence, warranting low confidence. ABBREVIATIONS: AI = adrenal insufficiency BMD = bone mineral density GC = glucocorticoids HC = hydrocortisone QoL = quality of life RCT = randomized controlled trial.

SURGICAL OUTCOMES OF PROLACTINOMAS IN RECENT ERA: RESULTS OF A HETEROGENOUS GROUP.

OBJECTIVE: Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas. METHODS: We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014. RESULTS: Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas. CONCLUSION: Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.

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: Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushing's syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor. METHODS: MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS: We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4, 95% CI: 0.95-12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS. CONCLUSIONS: Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.

Procedural and clinical outcomes of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy.

OBJECTIVE: The role of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy has not been fully investigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy. DESIGN: Single-centre, retrospective cohort study. PATIENTS AND MEASUREMENTS: Medical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a predefined reference standard. RESULTS: Biopsy was performed in 418 patients [62% men, median age 69 years (range, 15-91)] on 419 adrenal lesions, median size 3·1 cm (range, 0·6-24). The main indication for adrenal mass biopsy was (349/419, 83%) suspected adrenal metastasis from a known or suspected extra-adrenal primary source. Only 116 of 419, 28% of cases had prebiopsy biochemical testing for pheochromocytoma. Biopsy-related complications occurred in 4% of the patients. Histology revealed a metastasis in 231 of 419 (55%), benign adrenal tissue in 137 of 419 (33%), adrenocortical carcinoma in eight of 419 (2%), other lesions in 23 of 419 (5%) including seven cases of pheochromocytoma and six cases of infectious process. Biopsy was nondiagnostic in 20 of 419 (5%). All adrenal masses with unenhanced radiodensity ≤10 HU (42/137, 31%) proved to be benign adrenal adenomas. Adrenal biopsy diagnosed malignancy with a sensitivity of 88·5%, specificity of 91·5%, positive predictive value of 93·4% and negative predictive value of 85·5%. CONCLUSION: When used in the appropriate clinical setting, adrenal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malignancy. Efforts to increase awareness to perform biochemical testing for pheochromocytoma prior to adrenal biopsy are needed.

SELECTION OF ENDOCRINOLOGY SUBSPECIALTY TRAINEES: WHICH APPLICANT CHARACTERISTICS ARE ASSOCIATED WITH PERFORMANCE DURING FELLOWSHIP TRAINING?

OBJECTIVE: To determine which residency characteristics are associated with performance during endocrinology fellowship training as measured by competency-based faculty evaluation scores and faculty global ratings of trainee performance. METHODS: We performed a retrospective review of interview applications from endocrinology fellows who graduated from a single academic institution between 2006 and 2013. Performance measures included competency-based faculty evaluation scores and faculty global ratings. The association between applicant characteristics and measures of performance during fellowship was examined by linear regression. RESULTS: The presence of a laudatory comparative statement in the residency program director's letter of recommendation (LoR) or experience as a chief resident was significantly associated with competency-based faculty evaluation scores (ß = 0.22, P = .001; and ß = 0.24, P = .009, respectively) and faculty global ratings (ß = 0.85, P = .006; and ß = 0.96, P = .015, respectively). CONCLUSION: The presence of a laudatory comparative statement in the residency program director's LoR or experience as a chief resident were significantly associated with overall performance during subspecialty fellowship training. Future studies are needed in other cohorts to determine the broader implications of these findings in the application and selection process.

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

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.

PERFORMANCE OF FREE VERSUS TOTAL CORTISOL FOLLOWING COSYNTROPIN STIMULATION TESTING IN AN OUTPATIENT SETTING.

OBJECTIVE: Free cortisol (FC) is potentially superior to total cortisol (TC) measurements in selected clinical settings; however, the advantages of uniform use of FC in outpatient settings are unclear. The objectives of this study were to describe the dynamic response of FC during cosyntropin stimulation testing (CST) compared to TC and to determine the rates of discordance. METHODS: This is a cross-sectional study of 295 stable patients who underwent CST in an outpatient Endocrine Testing Center. The main outcome measures were TC and FC measurements during CST. RESULTS: The mean age of the 295 subjects was 49.1 (16.9) years. Of 218 females, 43 were taking estrogen therapy (ET) at the time of testing. Adrenal insufficiency (AI) was diagnosed in 41/295 (14%) patients. The FC concentrations were associated with TC concentrations at baseline (R(2) = 0.77, P<.001), 30 minutes (R(2) = 0.87, P<.001), and 60 minutes (R(2) = 0.90, P<.001). The FC cutoffs for AI were 873 and 1,170 ng/dL at 30 and 60 minutes, respectively. The FC had a more pronounced fold change from baseline to peak than TC (median 3.2 vs. 1.7, P<.001). Both TC and FC at baseline were higher in females on ET compared to those who were not and to males; however, peak TC and FC values were similar. In 3/43 females on ET, FC, and TC results were discordant (P = .003). CONCLUSION: We report 99% concordance of TC and FC measurements in a large outpatient cohort. The discordant rates were high in females treated with ET (7%). The FC measurements during CST in females on ET may provide a more rapid and accurate diagnosis of AI.

Chemical meningitis: a rare presentation of Rathke's cleft cyst.

Rathke's cleft cysts (RCC) are usually benign, sellar and/or suprasellar lesions originating from the remnants of Rathke's pouch. Rarely, RCC can present with chemical meningitis, sellar abscess, lymphocytic hypophysitis, or intracystic hemorrhage. We describe an unusual presentation of RCC in which the patient presented with a clinical picture of chemical meningitis consisting of meningeal irritation, inflammatory cerebrospinal fluid profile, and enhancing pituitary and hypothalamic lesions, in addition to involvement of the optic tracts and optic nerve.