Hepatobiliary and gastrointestinal manifestations of acromegaly.

Acromegaly is a unique condition characterized by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) hypersecretion usually due to a pituitary adenoma. Rarely, acromegaly can result from a GH-releasing hormone carcinoid or pancreatic neoplasm which stimulates the normal pituitary to secrete GH. This review describes the interactions between acromegaly and the gastrointestinal system. In contrast to the soft tissue and skeletal changes, clinical organomegaly of the liver, kidney, and spleen is unusual in patients with acromegaly and should warrant further investigations. The prevalence of cholelithiasis is notably increased by the use of the otherwise effective GH-lowering somatostatin analog, octreotide. Patients on long-term therapy with this agent may require anticholelithogenic treatment. The frequency of malignant and premalignant polyps of the colon justify the routine screening for these lesions in newly diagnosed patients with acromegaly.     

AIP Mutations are not Identified in Patients with Sporadic Pituitary Adenomas

The pathogenesis of pituitary adenomas remains a subject of interest. Recently, mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were identified as germline events leading to pituitary tumor predisposition in Finnish and Italian families with familial growth hormone-secreting pituitary adenomas and acromegaly. We examined the frequency of AIP mutations in pituitary tumors and blood of Canadian patients with sporadic pituitary somatotroph adenomas and sporadic pituitary adenomas of other types. Genomic DNA was extracted from pituitary tumors and white blood cells obtained from peripheral blood. Three PCR reactions were carried out to amplify the sites of known mutation, and amplified products were sequenced. AIP mutations were not detected as germline events in blood or as somatic alterations in tumors of 66 patients with pituitary adenomas. These included 50 acromegalics and 16 patients with other types of pituitary tumor. No mutations were detected in the blood of 22 controls and 10 patients with other endocrinopathies. Our results indicate that mutations in AIP are not identified in sporadic pituitary adenomas of Canadian patients. This rare mechanism of pituitary tumorigenesis appears to be unique to the initial Finnish and Italian families described. RD and SS contributed equally to this work.     

Complex Endocrinopathies in MEN-1: Diagnostic Dilemmas in Endocrine Oncology

Endocrine oncology is a complex area that must determine the site of a neoplastic process and the hormonal dysregulation that ensues. Patients with endocrine tumors often have delayed diagnosis because of the nonspecific and often subtle signs and symptoms. In patients with multiple endocrine neoplasia syndromes, diagnosis and clinicopathologic correlations can be even more challenging. We report a patient with multiple endocrine neoplasia type 1 (MEN-1) and a highly complex clinical story associated with multiple atypical lesions including two pituitary adenomas, a gonadotroph macroadenoma and a corticotroph microadenoma with Crooke's hyaline change and ectopic production of corticotropin-releasing hormone (CRH) from a thymic endocrine carcinoma. These lesions resulted in a highly complex clinical story, difficult diagnoses and questions about management. This case illustrates a number of clinically relevant challenges, including the diagnosis of pituitary adenomas in MEN-1, the difficulty in diagnosing Cushing's disease, and the large differential of pituitary pathologies in this disorder, double pituitary adenomas and other decoy lesions in Cushing's disease, the pathophysiology of Crooke's hyaline change in the pituitary, and the various causes of Cushing's syndrome associated with MEN-1.     

Immunodetection of collagen types I, II, III, and IV for differentiation of liver fibrosis stages in patients with chronic HCV

The current study is aimed at evaluating serum collagens and other serum biochemical markers as useful, non-invasive markers of hepatic fibrosis associated with chronic hepatitis C virus (HCV). Collagen types I, II, III, and IV were detected in serum using ELISA and Western blot techniques. The ELISA levels of collagen I, II, III, and IV increased significantly with the progression of fibrosis staging. Based on receiver-operating characteristic (ROC) curve analysis, the collagen type III (70 kDa) and type IV (200 kDa) were more useful than other serum bio-markers for differentiating severe fibrosis from mild fibrosis. Multivariate discriminant analysis (MDA) selected a fibrosis discriminant score (FDS) = [2.345 + Collagen III (microg/mL) x 1.923 + Collagen IV (microg/mL) x 1.544 + ALT (U/mL) x 0.005] - [albumin(g/L) x 0.046]. The FDS correctly classified 87% of the severe fibrosis patients at a cut-off score = 2.2 (i.e., more than 2.2 indicated severe fibrotic liver and less than 2.2 indicated mild fibrotic liver) with specificity of 97%. In a validation study, the FDS was applied to the second cohort of patients and the results were reproduced without significant difference. In conclusion, the developed four-parameter based FDS is useful for identifying severe liver fibrosis in patients with chronic HCV infection.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.     

How does esophagus look on barium esophagram in pediatric eosinophilic esophagitis?

Purpose

The clinical, endoscopic, and histologic findings of eosinophilic esophagitis (EoE) are well characterized; however, there have been very limited data regarding the radiologic findings of pediatric EoE. We report on the radiologic findings of pediatric EoE observed on barium esophagram and correlate them with the endoscopic findings.

Methods and materials

We identified children diagnosed with EoE in our center from 2004 to 2015. Two pediatric radiologists met after their independent evaluations of each fluoroscopic study to reach a consensus on each case. Clinical and endoscopic data were collected by retrospective chart review.

Results

Twenty-six pediatric EoE cases (age range 2–13 years; median 7.5 years) had barium esophagram done as part of the diagnostic approach for dysphagia. Thirteen children had abnormal radiologic findings of esophagus (50%): rings formation (n = 4), diffuse irregularity of mucosa (n = 8), fixed stricture formation (n = 3), and narrow-caliber esophagus (n = 10). Barium esophagram failed to show one of 10 cases of narrow-caliber esophagus and 10 of 14 cases of rings formation visualized endoscopically. The mean duration of symptoms prior to diagnosis of EoE was longer (3.7 vs. 1.7 year; p value 0.019), and the presentation with intermittent food impaction was commoner in the group with abnormal barium esophagram as compared to the group with normal barium esophagram (69% vs. 8%; p value 0.04).

Conclusion

Barium swallow study is frequently normal in pediatric EoE. With the exception of narrow-caliber esophagus, our data show poor correlation between radiologic and endoscopic findings.

     

Silent myocardial ischemia: Current perspectives and future directions

Silent myocardial ischemia (SMI) is increasingly being recognized as part of the spectrum of ischemic heart disease. The spectrum of SMI ranges from asymptomatic coronary artery disease to critical illness necessitating intensive care. Although many diagnostic tools have been used to identify low- and high-risk subgroups, their use is limited by modest sensitivities and specificities. The present review identifies current concepts in the management of SMI in various clinical settings, as well as emerging technologies that may simplify the diagnosis and treatment of this condition.