Early Recognition and Successful Treatment of Anti-synthetase Syndrome.

Anti-synthetase syndrome is an autoimmune disorder that is characterized by inflammatory myopathy, non-erosive polyarthritis, interstitial lung disease in addition to the presence of anti-aminoacyl t-RNA synthetase antibody. It can have variable presentations posing a major diagnostic challenge. Recognition of this syndrome is crucial for appropriate, timely therapy to prevent morbidity and mortality. We report the case of a 55-year-old male who initially presented to the emergency department (ED) with sudden onset shortness of breath, low-grade fever, dry cough, fatigue, and severe arthralgia. He was diagnosed with community-acquired pneumonia and was discharged with antibiotics. He then presented to his primary care physician (PCP) with worsening symptoms. A computed tomography (CT) scan of the chest showed the presence of patchy bilateral airspace opacities and infiltrates. He had elevated inflammatory markers and anti-nuclear antibodies (ANAs). Pulmonary function test (PFT) showed a restrictive pattern with a reduction in lung volumes. Further workup revealed the presence of anti-Jo-1 antibodies. In addition, a muscle biopsy was obtained which showed inflammatory myopathy. Lung biopsy was consistent with interstitial fibrosis. The diagnosis of the anti-synthetase syndrome was made and the patient was promptly started on high-dose prednisone and cyclophosphamide which was later switched to azathioprine and tacrolimus due to resistance and side effects. The patient's symptoms improved significantly with the current treatment without any other complications. This case highlights the importance of a thorough history and physical exam by PCP. Prompt communication and care coordination between PCP and specialists (rheumatologist and pulmonologist) are essential to expedite diagnostic testing and initiate treatment early in this disorder.

Escape MD: Using an Escape Room as a Gamified Educational and Skill-Building Teaching Tool for Internal Medicine Residents.

Purpose To create an innovative medicine-themed escape room (EsR) and assess its feasibility as a learner-centered educational model for medical trainees. This platform could be used to teach and reinforce medical knowledge as well as enhance team-building skills. Materials and Methods We created an internal medicine (IM) themed EsR, in which participants are locked and instructed to solve a series of puzzles using both medical and nonmedical concepts to "escape" the room within a given set of time. The players must use their critical thinking and communication skills to solve puzzles consisting of complex activities (such as image identification and object matching or retrieval) linked in a nonlinear pattern. A pre-activity survey was used to collect basic demographic information and initial perceptions of the activity. A post-activity survey consisting of a modified Likert scale and free-response questions was used to assess perceived activity use and satisfaction. The activity was followed by a debriefing session with a faculty member to reflect on individual and team-based learning. This study was approved by the Institutional Review Board. Results Each week, a group of four to seven residents participated in a one-hour long EsR session, which was replicated 15 times over five weeks, for a total of 86 internal medicine residents. 76 of 86 residents completed the post-activity survey. Overall, residents expressed a high level of satisfaction with the session (x̄ = 4.89), found it fun to play (x̄ = 4.89), and felt immersed in medicine (x̄ = 3.95). Residents thought the activity was most suitable for reinforcing knowledge (x̄ = 4.26) and greatly tested their communication skills (x̄ = 4.48).  Conclusion The medical EsR experience was enjoyed by the vast majority of residents with very positive oral and survey feedback. Hence, we successfully created an active, learner-centered, gamified teaching tool that can be used for teaching/reinforcing medical concepts in a fun, competitive, and team-building format. The EsR, as a teaching tool, can be replicated with ease several times and requires very few resources to create.

Abnormal body composition in patients with adrenal adenomas.

OBJECTIVE: Increased visceral fat and sarcopenia are cardiovascular risk factors that may explain increased cardiovascular morbidity and frailty in patients with adrenal adenomas. Our objective was to compare body composition measurement of patients with adrenal adenomas to referent subjects without adrenal disease. DESIGN: Cross-sectional study, 2014-2018. METHODS: Participants were adults with nonfunctioning adrenal tumor (NFAT), mild autonomous cortisol secretion (MACS), and Cushing syndrome (CS) and age, sex, and BMI 1:1 matched referent subjects without adrenal disorders. Main outcome measures were body composition measurements calculated from abdominal CT imaging. Intra-abdominal adipose tissue and muscle mass measurements were performed at the third lumbar spine level. RESULTS: Of 227 patients with adrenal adenomas, 20 were diagnosed with CS, 76 with MACS, and 131 with NFAT. Median age was 56 years (range: 18-89), and 67% were women. When compared to referent subjects, patients with CS, MACS, and NFAT demonstrated a higher visceral fat (odds ratio (OR): 2.2 (95% CI: 0.9-6.5), 2.0 (1.3-3.2), and 1.8 (1.2-2.7) and a lower skeletal muscle area (OR: 0.01 (95% CI: 0-0.09), 0.31 (0.18-0.49), and 0.3 (1.2-2.7)) respectively. For every 1 µg/dL cortisol increase after overnight dexamethasone, visceral fat/muscle area ratio increased by 2.3 (P = 0.02) and mean total skeletal muscle area decreased by 2.2 cm2 (P = 0.03). CONCLUSION: Patients with adrenal adenomas demonstrate a lower muscle mass and a higher proportion of visceral fat when compared to referent subjects, including patients with NFAT. Even a subtle abnormality in cortisol secretion may impact health of patients with adenomas.

Natural History of Adrenal Incidentalomas With and Without Mild Autonomous Cortisol Excess: A Systematic Review and Meta-analysis.

Background: Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear. Purpose: To summarize the follow-up data of adults with NFAT or MACE to determine the proportions of tumor growth, malignant transformation, and incident changes in hormone function; the prevalence of incident cardiometabolic comorbid conditions; and mortality. Data Sources: MEDLINE, Embase, Cochrane, and Scopus (January 1990 to February 2019) and bibliographies of identified articles, without language restriction. Study Selection: Studies that included 20 or more conservatively managed patients with NFAT or MACE and reported outcomes at baseline and after at least 12 months of follow-up. Data Extraction: Pairs of reviewers extracted outcomes and assessed methodological quality. Data Synthesis: Thirty-two studies reported outcomes of 4121 patients with NFAT or MACE, 61.5% of whom were women; the mean age was 60.2 years, and mean follow-up was 50.2 months. Mean tumor growth was 2 mm over 52.8 months. Clinically significant tumor enlargement (≥10 mm) occurred in 2.5% of patients, and none developed adrenal cancer. Clinically overt hormone excess was unlikely to develop (<0.1%) in patients with NFAT or MACE. Only 4.3% of patients with NFAT developed MACE, and preexisting MACE was unlikely to resolve (<0.1%). Hypertension, obesity, dyslipidemia, and type 2 diabetes were highly prevalent (60.0%, 42.0%, 33.7%, and 18.1% of patients, respectively) and were more likely to develop and worsen in MACE than NFAT. New cardiovascular events were more prevalent in MACE (15.5%) than NFAT (6.4%). Mortality was 11.2% and was similar between NFAT and MACE. Limitation: Evidence was scarce, and definitions of MACE and comorbid conditions were heterogeneous. Conclusion: During follow-up, NFAT and MACE do not show clinically relevant changes in size or hormonal function, but they may carry an increased risk for cardiometabolic comorbid conditions. Primary Funding Source: None.

Comparison of plasma and urinary microRNA-483-5p for the diagnosis of adrenocortical malignancy.

INTRODUCTION: Minimally invasive circulating microRNAs might be used for the preoperative differentiation of adrenocortical carcinoma (ACC) and adrenocortical adenoma (ACA). So far, the best blood-borne microRNA biomarker of ACC is circulating hsa-miR-483-5p. The expression of urinary hsa-miR-483-5p as a non-invasive marker of malignancy and its correlation with plasma hsa-miR-483-5p, has not been investigated, yet. AIM: Our aim was to investigate the expression of urinary hsa-miR-483-5p and its correlation with its plasma counterpart. METHODS: Plasma and urinary samples from 23 ACC and 23 ACA patients were analysed using real-time RT-qPCR. To evaluate the diagnostic applicability of hsa-miR-483-5p, ROC-analysis was performed. RESULTS: Significant overexpression of hsa-miR-483-5p was observed in carcinoma patients' plasma samples compared to adenoma patients' (p < 0.0001, sensitivity: 87%, specificity: 78.3%). In urinary samples, however, no significant difference could be detected between ACC and ACA patients. CONCLUSIONS: Plasma hsa-miR-483-5p has been confirmed as significantly overexpressed in adrenocortical cancer patients and thus might be exploited as a minimally invasive preoperative marker of malignancy. The applicability of urinary hsa-miR-483-5p for the diagnosis of adrenocortical malignancy could not be confirmed.

CT Characteristics of Pheochromocytoma: Relevance for the Evaluation of Adrenal Incidentaloma.

Background: Up to 7% of all adrenal incidentalomas (AIs) are pheochromocytomas (PCCs). In the evaluation of AI, it is generally recommended that PCC be excluded by measurement of plasma-free or 24-hour urinary fractionated metanephrines. However, recent studies suggest that biochemical exclusion of PCC not be performed for lesions with CT characteristics of an adrenocortical adenoma (ACA). Aim: To determine the proportion of PCCs with ACA-like attenuation or contrast washout on CT. Methods: For this multicenter retrospective study, two central investigators independently analyzed the CT reports of 533 patients with 548 histologically confirmed PCCs. Data on tumor size, unenhanced Hounsfield units (HU), absolute percentage washout (APW), and relative percentage washout (RPW) were collected in addition to clinical parameters. Results: Among the 376 PCCs for which unenhanced attenuation data were available, 374 had an attenuation of >10 HU (99.5%). In the two exceptions (0.5%), unenhanced attenuation was exactly 10 HU, which lies just within the range of ≤10 HU that would suggest a diagnosis of ACA. Of 76 PCCs with unenhanced HU > 10 and available washout data, 22 (28.9%) had a high APW and/or RPW, suggestive of ACA. Conclusion: Based on the lack of PCCs with an unenhanced attenuation of <10 HU and the low proportion (0.5%) of PCCs with an attenuation of 10 HU, it seems reasonable to abstain from biochemical testing for PCC in AIs with an unenhanced attenuation of ≤10 HU. The assessment of contrast washout, however, is unreliable for ruling out PCC.