Anti-RET monoclonal antibody, clone SN-1161-5H2

Multiple endocrine neoplasia type 2 (MEN2) is a rare hereditary syndrome due to mutations of the proto-oncogene REarranged during Transfection (RET), defined by the association of medullary thyroid carcinoma (MTC) in almost 100% cases, and pheochromocytoma in roughly 50% (primary hyperparathyroidism can be seen in 10-20% of patients with MEN2A). Early thyroidectomy and the efficacy of novel tyrosine kinase inhibitors modified the natural history of MTC, with possibilities of cure or long-term control. The second main compound, pheochromocytoma, is reported with a variable penetrance, from 10 to 80% cases, depending on the mutation of RET. Pheochromocytoma constitutes the main disease to screen in patients with RET mutations. Pheochromocytoma clinical and biochemical diagnosis, as well as the way to treat it are thus crucial. This review will thus focus on the epidemiological specificities of MEN2-related pheochromocytoma, the genotype/phenotype relationship, the modern imaging modalities necessary to confirm the diagnosis in this hereditary context, as well as the optimal management and the possibilities of adrenal sparing surgery. Additional information will include the natural history of MEN2B-pheochromocytoma, the rare cases of malignant pheochromocytoma, and the factors that could modify the penetrance between individuals carrying the same mutation, especially in the same family.

Objectives: Diagnosing disturbances in iron metabolism can be challenging when accompanied by inflammation. New diagnostic tools such as the "Thomas-plot" (TP) (relation of soluble transferrin receptor [sTfR]/log ferritin to reticulocyte hemoglobin content [RET-H-e]) were established to improve classification of anemias. Aim of this retrospective study was to assess the added diagnostic value of the TP in anemia work up. Methods: Patients from December 2016 to September 2018 with a complete blood count, iron status, RET-H-e and sTfR were manually classified into the four quadrants of the TP on basis of conventional iron markers. Manual and algorithm-based classifications were compared using cross tabulations, Box-Whisker-Plots as well as Receiver-Operating-Characteristics (ROC) to calculate the diagnostic accuracy using Area under the Curve (AUC) analysis. Results: A total of 3,745 patients with a conventional iron status, including 1,721 TPs, could be evaluated. In 70% of the cases the manual classification was identical to the TP, in 10% it was deviant. 20% could not clearly be classified, mostly due to inflammatory conditions. In the absence of an inflammatory condition, ferritin was a reliable parameter to define iron deficiency (ID) (AUC 0.958). In the presence of inflammation, the significance of the ferritin index (AUC 0.917) and of the RET-H-e (AUC 0.957) increased. Conclusions: The TP can be useful for narrowing down the causes of anemia in complex cases. Further studies with focus on special patient groups, e.g., oncological or rheumatic patients, are desirable.