Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation.

BACKGROUND: MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome. CASE PRESENTATION: We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.Gly225Aspfs*56 in exon 4 of the MEN1 gene. Diagnosis and clinical phenotyping of MEN1 was established by laboratory tests, ultrasound, biopsy, MRI imaging and endosonography. The clinical course of the disease was followed in the index patient and her family members for eight years. The mutation was associated with distinct clinical phenotypes in the index patient and three family members harboring p.Gly225Aspfs*56. Family members affected showed primary hyperparathyroidism but variable patterns of associated endocrine tumors, adrenal cortical adenomas, prolactinoma, multifocal pancreatic neuroendocrine tumors, insulinoma and nonsecretory neuroendocrine tumors of the pancreas. The mutation c.674delG; p.Gly225Aspfs*56 leads to a frameshift from codon 225 with early truncation of the menin protein. In silico analysis predicts loss of multiple protein-menin interactions in p.Gly225Aspfs*56, potentially rendering menin insufficient to control cell division and replication. However, no aggressive neuroendocrine tumors were observed in the follow-up of this family. CONCLUSIONS: We report a novel heterozygous MEN1 frameshift mutation, potentially causing (at least partial) inactivation of menin tumor suppression potential but lacking a genotype-phenotype correlation. Our study highlights the importance of personalized care with appropriate testing and counseling in MEN1 families.

Comparison of strain elastography, point shear wave elastography using acoustic radiation force impulse imaging and 2D-shear wave elastography for the differentiation of thyroid nodules.

PURPOSE: The aim of the study was to compare three different elastography methods, namely Strain Elastography (SE), Point Shear-Wave Elastography (pSWE) using Acoustic Radiation Force Impulse (ARFI)-Imaging and 2D-Shear Wave Elastography (2D-SWE), in the same study population for the differentiation of thyroid nodules. MATERIALS AND METHODS: All patients received a conventional ultrasound scan, SE and 2D-SWE, and all patients except for two received ARFI-Imaging. Cytology/histology of thyroid nodules was used as a reference method. SE measures the relative stiffness within the region of interest (ROI) using the surrounding tissue as reference tissue. ARFI mechanically excites the tissue at the ROI using acoustic pulses to generate localized tissue displacements. 2D-SWE measures tissue elasticity using the velocity of many shear waves as they propagate through the tissue. RESULTS: 84 nodules (73 benign and 11 malignant) in 62 patients were analyzed. Sensitivity, specificity and NPV of SE were 73%, 70% and 94%, respectively. Sensitivity, specificity and NPV of ARFI and 2D-SWE were 90%, 79%, 98% and 73%, 67%, 94% respectively, using a cut-off value of 1.98m/s for ARFI and 2.65m/s (21.07kPa) for 2D-SWE. The AUROC (Area under the Receiver Operating Characteristic) of SE, ARFI and 2D-SWE for the diagnosis of malignant thyroid nodules were 52%, 86% and 71%, respectively. A significant difference in AUROC was found between SE and ARFI (p = 0.008), while no significant difference was found between ARFI and SWE (86% vs. 71%, p = 0.31), or SWE and SE (71% vs. 52%, p = 0.26). CONCLUSION: pSWE using ARFI and 2D-SWE showed comparable results for the differentiation of thyroid nodules. ARFI was superior to elastography using SE.

Transient elastography with a new probe for obese patients for non-invasive staging of non-alcoholic steatohepatitis.

OBJECTIVE: Transient elastography (TE) has shown promising results for the staging of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) with the limitation that 25% of obese patients cannot be examined with the standard TE probe. The aim of this study was to evaluate a new XL probe for obese patients for the staging of liver fibrosis in NAFLD/NASH. METHODS: Fifty patients with NAFLD/NASH and histological assessment of liver fibrosis were included in the study. All patients received TE with the standard probe (M probe) and the new XL probe, and the results were compared with liver histology. RESULTS: The diagnostic accuracy expressed as the area under the ROC curve for TE measurements with the M probe and the XL probe was 0.80 and 0.82 for the diagnosis of significant fibrosis, and 0.91 and 0.95 for the diagnosis of liver cirrhosis, respectively. Eighty-three percent of the patients who could not be measured with the M probe could be measured using the XL probe. CONCLUSION: Transient elastography using the XL probe for obese patients can be performed with comparable diagnostic accuracy to the standard probe and enables the examination of significantly more obese patients.