Pancreatic ACTH Hypersecretion and Pituitary Macroadenoma.

A 55-year-old woman admitted for hypertensive emergency and myocardial infarction reported weight gain, muscle weakness, easy bruising, and recent-onset diabetes in the past 3 to 12 months. Urinary and salivary cortisol and adrenocorticotropin hormone (ACTH) levels were elevated. Pituitary imaging detected a macroadenoma. ACTH and cortisol did not increase after corticotropin-releasing hormone administration. Imaging revealed a large pancreatic mass. Pathology indicated a well-differentiated World Health Organization (WHO) grade 2 distal pancreatic neuroendocrine neoplasm which stained for ACTH by immunohistochemistry. Postoperatively, Cushing manifestations resolved, ACTH and cortisol levels became low, and patient required hydrocortisone replacement for 7 months. During the 3.5 years of follow-up, the pituitary macroadenoma size remained stable and pituitary hormone axes other than ACTH remained normal. This extremely rare case of ectopic ACTH-secreting pancreatic neuroendocrine tumor coexisting with a nonfunctioning pituitary macroadenoma illustrates the importance of dynamic endocrine testing in Cushing syndrome.

CHRONIC ETHANOL USE WORSENS GUT PERMEABILITY AND ALTERS TIGHT JUNCTION EXPRESSION IN A MURINE SEPSIS MODEL.

ABSTRACT: Alcohol use disorder is associated with increased mortality in septic patients. Murine studies demonstrate that ethanol/sepsis is associated with changes in gut integrity. This study examined intestinal permeability after ethanol/sepsis and investigated mechanisms responsible for alterations in barrier function. Mice were randomized to drink either 20% ethanol or water for 12 weeks and then were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability was disproportionately increased in ethanol/septic mice via the pore, leak, and unrestricted pathways. Consistent with increased permeability in the leak pathway, jejunal myosin light chain (MLC) kinase (MLCK) expression and the ratio of phospho-MLC to total MLC were both increased in ethanol/CLP. Gut permeability was altered in MLCK -/- mice in water/CLP; however, permeability was not different between WT and MLCK -/- mice in ethanol/CLP. Similarly, jejunal IL-1ß levels were decreased while systemic IL-6 levels were increased in MLCK -/- mice in water/CLP but no differences were identified in ethanol/CLP. While we have previously shown that mortality is improved in MLCK -/- mice after water/CLP, mortality was significantly worse in MLCK -/- mice after ethanol/CLP. Consistent with an increase in the pore pathway, claudin 4 levels were also selectively decreased in ethanol/CLP WT mice. Furthermore, mRNA expression of jejunal TNF and IFN-γ were both significantly increased in ethanol/CLP. The frequency of CD4 + cells expressing TNF and IL-17A and the frequency of CD8 + cells expressing IFN-γ in Peyer's Patches were also increased in ethanol/CLP. Thus, there is an ethanol-specific worsening of gut barrier function after CLP that impacts all pathways of intestinal permeability, mediated, in part, via changes to the tight junction. Differences in the host response in the setting of chronic alcohol use may play a role in future precision medicine approaches toward the treatment of sepsis.

Hepatocellular Carcinoma With Atypical Imaging Features: Review of the Morphologic Hepatocellular Carcinoma Subtypes With Radiology-Pathology Correlation.

Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer death in the United States with the incidence rate more than doubling in 20 years. HCC is unique since a noninvasive diagnosis can be achieved with imaging alone when specific clinical criteria and imaging characteristics are met, obviating the need for tissue sampling. However, HCC is a highly heterogeneous neoplasm. Atypical HCC subtypes vary significantly in their morphology, which can be attributed to specific histologic and molecular features, and can cause deviations from the classic imaging characteristics. The different morphologic subtypes of HCC frequently present a diagnostic challenge for radiologists and pathologists since their imaging and pathologic features can overlap with those of non-HCC malignancies. Identifying an atypical subtype can have important clinical implications. Liver transplant, albeit a scarce and limited resource, is the optimal treatment for conventional HCC, potentially curing both the tumor and the underlying pre-malignant condition. Some HCC subtypes as well as mimickers are associated with unacceptably high recurrence and poor outcome after transplant, and there remains limited data on the role and prognosis of liver transplantation for treatment of rare HCC subtypes. Other subtypes tend to recur later than classic HCC, potentially requiring a different follow-up scheme. This review will discuss the appearance of different HCC subtypes in relation to their histopathologic features. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.