Context Molecular tests have improved the accuracy of preoperative diagnosis of indeterminate thyroid nodules. The Afirma Gene Sequencing Classifier (GSC) was developed to improve the specificity of the Gene Expression Classifier (GEC). Independent studies are needed to assess the performance of GSC. Objective The aim was to compare the performance of GEC and GSC in the assessment of indeterminate nodules. Design, Settings, and Participants Retrospective analysis of Bethesda III and IV nodules tested with GEC or GSC in an academic center between December 2011 and September 2018. Benign call rates (BCRs) and surgical outcomes were compared. Histopathologic data were collected on nodules that were surgically resected to calculate measures of test performance. Results The BCR was 41% (73/178) for GEC and 67.8% (82/121) for GSC (P < .001). Among specimens with dominant Hürthle cell cytology, the BCR was 22% (6/27) for GEC and 63.2% (12/19) for GSC (P = .005). The overall surgery rate decreased from 47.8% in the GEC group to 34.7% in the GSC group (P = .025). One GEC-benign and 3 GSC-benign nodules proved to be malignant on surgical excision. GSC had a statistically significant higher specificity (94% vs 60%, P < .001) and positive predictive value (PPV) (85.3% vs 40%, P < .001) than GEC. While sensitivity and negative predictive value (NPV) dropped with GSC (97.0% vs 90.6% and 98.6% vs 96.3%, respectively), these differences were not significant. Conclusions GSC reclassified more indeterminate nodules as benign and improved the specificity and PPV of the test. These enhancements appear to be resulting in fewer diagnostic surgeries.

Objective Diabetes mellitus is associated with microvascular and macrovascular complications; the most commonly recognized ones include diabetic nephropathy, retinopathy, and neuropathy. Less well-known complications are equally important, as timely recognition and treatment are essential to decrease short- and long-term morbidity. Methods Herein, we describe a case of a 41-year-old female with longstanding, uncontrolled type 2 diabetes, who presented with classical findings of diabetic myonecrosis. Results Our patient underwent extensive laboratory and imaging studies prior to diagnosis due to its rarity and similarity in presentation with other commonly noted musculoskeletal conditions. We emphasize the clinical presentation, laboratory and imaging findings, treatment regimen, and prognosis associated with diabetic myonecrosis. Conclusion Diabetic myonecrosis is a rare complication of longstanding, poorly controlled diabetes mellitus. The diagnosis requires a high index of suspicion in the right clinical setting: acute onset nontraumatic muscular pain with associated findings on clinical exam, laboratory studies, and imaging. While the short-term prognosis is good, the recurrence rate remains high and long-term prognosis is poor given underlying uncontrolled diabetes and associated sequelae.

Summary Ectopic adrenocorticotropic hormone (ACTH) production leading to ectopic ACTH syndrome accounts for a small proportion of all Cushing’s syndrome (CS) cases. Thymic neuroendocrine tumors are rare neoplasms that may secrete ACTH leading to rapid development of hypercortisolism causing electrolyte and metabolic abnormalities, uncontrolled hypertension and an increased risk for opportunistic infections. We present a unique case of a patient who presented with a mediastinal mass, revealed to be an ACTH-secreting thymic neuroendocrine tumor (NET) causing ectopic CS. As the diagnosis of CS from ectopic ACTH syndrome (EAS) remains challenging, we emphasize the necessity for high clinical suspicion in the appropriate setting, concordance between biochemical, imaging and pathology findings, along with continued vigilant monitoring for recurrence after definitive treatment. Learning points: Functional thymic neuroendocrine tumors are exceedingly rare. Ectopic Cushing’s syndrome secondary to thymic neuroendocrine tumors secreting ACTH present with features of hypercortisolism including electrolyte and metabolic abnormalities, uncontrolled hypertension and hyperglycemia, and opportunistic infections. The ability to undergo surgery and completeness of resection are the strongest prognostic factors for improved overall survival; however, the recurrence rate remains high. A high degree of initial clinical suspicion followed by vigilant monitoring is required for patients with this challenging disease.

Objective: Pituitary adenomas have a population prevalence of less than 0.1%. They can rarely present with serious complications, such as pituitary tumor apoplexy with symptoms of sudden severe headache, vision impairment, nausea, and vomiting. Methods: To date, there has been no proven underlying mechanism for the development of pituitary apoplexy. We report a novel association between pituitary tumor apoplexy and influenza A, indicating an inflammatory pathology underlying influenza infection contributing to hemorrhage. Results: Our patient is a 44-year-old female with past medical history of hypertension and diabetes mellitus type 2 who presented with a 2-day history of visual deficits, progressively worsening headache, and dizziness. She reported fever, chills, myalgia, and cough and tested positive for influenza A. Magnetic resonance imaging of the brain revealed a large suprasellar macroadenoma with internal hemorrhage. She underwent emergent transsphenoidal excision of pathology-proven pituitary adenoma with apoplexy. Signs of the syndrome of inappropriate antidiuretic hormone and diabetes insipidus were frequent

Background: To examine the clinical and hormonal profiles, comorbidities, treatment patterns, surgical pathology and clinical outcomes of patients diagnosed with acromegaly at the Cleveland Clinic over a 15-year period. Methods: A retrospective chart review of patients with acromegaly who underwent surgical resection between 2003 and 2018. Results: A total of 136 patients (62 men; mean age 48.1 years) with biochemical evidence of acromegaly were analyzed. Median insulin-like growth factor 1 (IGF-1) level at diagnosis was 769.0 ng/mL and most patients had a macroadenoma (82.2%). Immunoreactivity to growth hormone (GH) was noted in 124 adenomas, with co-staining in 89 adenomas. Complete visible tumor resection during initial surgery was achieved in 87 patients (64.0%). In this cohort, complete response to surgery alone was observed in 61 patients (70.1%), while 31 out of 65 patients (47.7%) who received additional post-surgical medications and/or radiation therapy achieved complete response. At most recent follow-up, 92 patients achieved eventual complete response by documented normalization of IGF-1 levels. Higher IGF-1 level at diagnosis (P = 0.024) and cavernous sinus invasion (P = 0.028) were predictors for failure to respond to surgery. Conclusion: In this study, the majority of tumors were macroadenoma, plurihormonal, and treated effectively with surgery alone or surgery with adjuvant medical or radiation therapy. More studies are needed to identify additional molecular biomarkers, tumor characteristics and imaging findings to individualize treatment and better predict treatment outcomes.

Diabetes mellitus is a leading risk factor for cardiovascular disease with rising prevalence and disease burden. The microvascular and macrovascular complications of diabetes are well-recognized and include increased risk of cardiovascular disease, myocardial infarction, and stroke. Newer diabetes medications have demonstrated significant cerebrovascular, cardiovascular, renal, and mortality benefits in high risk patients with diabetes. In addition to their glucose-lowering effects, the thiazolidinedione pioglitazone, SGLT2 inhibitors, GLP-1 agonist, and DPP-4 inhibitors have demonstrated significant cerebrovascular, cardiovascular, renal, and mortality effects. The outcomes and safety data of newer diabetes medications from recent trials demonstrate cardiovascular and mortality effects with significant implications for clinical practice.

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